福泰製藥 (VRTX) 2016 Q2 法說會逐字稿

Good evening. This is Michael Partridge, Vice President of Investor Relations for Vertex. Welcome to our second-quarter 2016 financial results conference call.

晚安.這是 Vertex 公司投資者關係副總裁 Michael Partridge。歡迎參加我們2016年第二季財務業績電話會議。

(Caller Instructions)

（來電者指示）

You can access the webcast slides by going to our website, where a replay will also be available later tonight. Dr. Jeff Leiden, Chairman and CEO, and Ian Smith, Chief Financial Officer, will provide prepared remarks this evening. They will be joined by Stuart Arbuckle, Chief Commercial Officer, and Dr. Jeff Chodakewitz, Chief Medical Officer, for the Q&A portion of the conference call.

您可以造訪我們的網站查看網路直播幻燈片，今晚晚些時候還可以觀看回放。董事長兼執行長傑夫萊頓博士和財務長伊恩史密斯將於今晚發表準備好的演講。商務長史都華·阿巴克爾和首席醫療官傑夫·喬達克維茨博士將加入電話會議的問答環節。

We will make forward-looking statements on this conference call. These statements are subject to the risks and uncertainties discussed in detail in today's press release and our 10-K, which has been filed with the SEC. The statements including without limitation those regarding the ongoing development and potential commercialization of our drug candidates, our expectations regarding our approved medicines, and Vertex's future financial performance are based on management's current assumptions. Actual outcomes and events could differ materially.

我們將在本次電話會議上發表一些前瞻性聲明。這些聲明受到今天新聞稿和我們向美國證券交易委員會提交的 10-K 文件中詳細討論的風險和不確定性的影響。包括但不限於有關我們候選藥物的持續開發和潛在商業化、我們對已獲批准藥物的預期以及Vertex未來財務業績的聲明，均基於管理層目前的假設。實際結果和事件可能與此有重大差異。

Information regarding our use of GAAP and non-GAAP financial measures, and a reconciliation of GAAP to non-GAAP is available in tonight's press release. I would also refer you to slide 4 of tonight's webcast. I will now turn the call over to Dr. Jeff Leiden.

有關我們使用 GAAP 和非 GAAP 財務指標的信息，以及 GAAP 與非 GAAP 的調整表，請參閱今晚的新聞稿。我還想請您參考今晚網路直播的第 4 張投影片。現在我將把電話交給傑夫·萊頓博士。

Thanks, Michael. Good evening, everyone. It was just over one year ago that we received FDA approval for ORKAMBI, marking the most significant step to date in our journey to develop new medicines for people with cystic fibrosis. Tonight, I'm pleased to report on our significant and steady progress in CF, and I'll review three key phases on efforts to bring all people with CF medicines to treat the underlying cause of their disease. If we're successful in these efforts, we believe significant and sustained revenue and earnings growth will follow.

謝謝你，麥可。各位晚上好。就在一年多前，我們獲得了 FDA 對 ORKAMBI 的批准，這標誌著我們在為囊性纖維化患者開發新藥的旅程中邁出了迄今為止最重要的一步。今晚，我很高興地向大家報告我們在囊性纖維化治療方面取得的重大而穩定的進展，我將回顧三個關鍵階段的工作，這些工作旨在讓所有囊性纖維化患者都能獲得藥物，從而治療其疾病的根本原因。如果我們這些努力取得成功，我們相信收入和利潤將實現顯著且持續的成長。

Today there are approximately 27,000 people eligible for treatment with ORKAMBI or KALYDECO; however we're only treating approximately 9,000 or one-third of these patients. The first and most significant near-term step to increase the number of eligible patients being treated with our medicines is to gain reimbursement ORKAMBI in key European and other countries. Progress with reimbursement for ORKAMBI would enable the vast majority of currently eligible patients be treated with one of our CF medicines.

目前約有 27,000 人符合接受 ORKAMBI 或 KALYDECO 治療的條件；然而，我們只治療了約 9,000 名患者，即其中三分之一的患者。增加接受我們藥物治療的合格患者數量的首要且最重要的近期步驟是在歐洲主要國家和其他國家獲得 ORKAMBI 的報銷。ORKAMBI 的報銷進展將使目前絕大多數符合條件的患者能夠使用我們的一種 CF 藥物進行治療。

The second step to treat more people with CF is to further expand the labels for both ORKAMBI and KALYDECO, which could increase the total number of eligible patients from 27,000 to approximately 44,000. And the third step is to potentially treat all people with CF with new combinations of CFTR modulators, as well as other approaches to treatment, such as in ENaC inhibition, gene editing, and mRNA therapies.

治療更多 CF 患者的第二步是進一步擴大 ORKAMBI 和 KALYDECO 的適應症範圍，這可能會使符合條件的患者總數從 27,000 人增加到約 44,000 人。第三步是有可能用新的 CFTR 調節劑組合以及其他治療方法（如 ENaC 抑制、基因編輯和 mRNA 療法）來治療所有 CF 患者。

First, to reimbursement for ORKAMBI. Outside the US, the reimbursement process is ongoing, and these discussions are progressing as anticipated across Europe, Canada, and Australia. We are encouraged that many reimbursement authorities have acknowledged the significant clinical benefits that ORKAMBI provides. We believe that we will achieve reimbursement from European and other government payers, just as we've seen in the US. We look forward to updating you as we obtain reimbursement in key countries going forward.

首先，要報銷 ORKAMBI 的費用。在美國以外，報銷流程仍在進行中，歐洲、加拿大和澳洲的討論也如預期般進展順利。我們感到欣慰的是，許多健保機構已經認可了 ORKAMBI 所帶來的顯著臨床益處。我們相信，我們將像在美國一樣，從歐洲和其他國家的政府支付方獲得報銷。我們期待在未來獲得主要國家的報銷後及時向您報告最新進展。

Second, to our label expansion efforts for both ORKAMBI and KALYDECO. Specifically, there's some 12,000 additional patients younger than age 12 with two copies of the delta F508 mutation, who we believe could be helped ORKAMBI. In the second quarter, the FDA accepted for review our supplement new drug applications for the use of ORKAMBI in children ages 6 to 11, and granted our request for priority review, setting a target review date or PDUFA date of September 30, 2016. If approved, we expect to be ready to bring ORKAMBI to these patients immediately following approval.

其次，我們致力於擴大 ORKAMBI 和 KALYDECO 的標籤範圍。具體來說，還有大約 12,000 名 12 歲以下的患者攜帶兩個 delta F508 突變拷貝，我們相信 ORKAMBI 可以幫助他們。第二季度，FDA 受理了我們關於 ORKAMBI 用於 6 至 11 歲兒童的補充新藥申請，並批准了我們的優先審查請求，將目標審查日期或 PDUFA 日期設定為 2016 年 9 月 30 日。如果獲得批准，我們預計在獲得批准後即可立即為這些患者提供 ORKAMBI。

In parallel, we also progressing with our efforts to bring ORKAMBI to children ages 6 to 11 in Europe, where we plan to submit our application for approval in the first half of next year, following the conclusion of our fully enrolled Phase III efficacy and safety study in this group of patients. We estimate that there are approximately 2,400 children ages 6 to 11 in the US, and 3,400 in Europe, who would be eligible for ORKAMBI.

同時，我們也努力將 ORKAMBI 帶給歐洲 6 至 11 歲的兒童，我們計劃在明年上半年提交審批申請，此前我們已完成了針對該組患者的 III 期療效和安全性研究。我們估計，美國約有 2400 名 6 至 11 歲的兒童，歐洲約有 3400 名 6 至 11 歲的兒童符合 ORKAMBI 的資格。

There are approximately 5,000 additional patients in North America, Europe, and Australia, largely those with residual function mutations, who could be helped by KALYDECO. While we received a complete response letter from the FDA earlier this year regarding our application for approval of KALYDECO in people with CF ages 2 and older, who have one of 23 residual function mutations, our belief that KALYDECO would be beneficial to these patients is unchanged, and we continue to pursue FDA approval for these patients, as soon as possible. There are approximately 1,500 people with CF in the US who have the mutations included in our residual function SNDA.

北美、歐洲和澳洲還有大約 5,000 名患者，其中大部分是存在殘餘功能突變的患者，KALYDECO 可以幫助他們。雖然我們今年早些時候收到了 FDA 對我們申請批准 KALYDECO 用於 2 歲及以上患有 CF 且攜帶 23 種殘餘功能突變之一的患者的申請的完整回复函，但我們仍然相信 KALYDECO 對這些患者爭取，我們將繼續盡快盡快對 FDA 對這些患者的批准。美國約有 1500 名 CF 患者攜帶我們殘餘功能 SNDA 中所包含的突變。

And third to our expanding pipeline of investigational CF medicine. The most advanced pipeline program in CF is our broad Phase III program for VX-661, in combination with ivacaftor. VX-661 plus ivacaftor may have an improved benefit risk profile compared to ORKAMBI in people with two copies of the delta F508 mutation, and may provide enhanced clinical benefits over ivacaftor monotherapy for other patients with gating mutations.

第三，我們不斷擴充的囊性纖維化研究藥物研發管線。目前，CF 領域最先進的研發管線計畫是 VX-661 與 ivacaftor 合併治療的廣泛 III 期臨床試驗計畫。對於攜帶兩個 delta F508 突變拷貝的患者，VX-661 加 ivacaftor 可能比 ORKAMBI 具有更好的獲益風險比，並且對於其他攜帶門控突變的患者，VX-661 加 ivacaftor 可能比 ivacaftor 單藥治療提供更強的臨床獲益。

Enrollment in the study of VX-661 plus ivacaftor in people ages 12 and older with two copies of the delta F508 mutation is expected to complete in August. Data from this six-month study are expected in the first half of 2017. The other three Phase III studies of VX-661 are also progressing as planned.

針對 12 歲及以上且攜帶兩個 delta F508 突變拷貝的人群，VX-661 加 ivacaftor 的研究招募工作預計將於 8 月完成。這項為期六個月的研究數據預計將於 2017 年上半年公佈。VX-661 的其他三項 III 期研究也按計劃進行。

We plan to submit a new drug application to the US FDA for VX-661 in combination with ivacaftor in the second half of 2017. Importantly, VX-661 is also positioned to play a key role in the triple combination regimen with the next-generation corrector and ivacaftor. We believe that this triple combination approach may allow us to treat an additional large group of patients, specifically those with one delta F508 mutation and one mutation that results in minimal CFTR function. These patients do not currently have a medicine to treat the cause of their disease.

我們計劃於 2017 年下半年向美國 FDA 提交 VX-661 與 ivacaftor 聯合用藥的新藥申請。重要的是，VX-661 也將在與下一代矯正器和伊伐卡託的三聯療法中發揮關鍵作用。我們相信，這種三重療法或許能夠讓我們治療更多的患者，特別是那些攜帶一個 delta F508 突變和一個導致 CFTR 功能極低的突變的患者。這些患者目前還沒有藥物可以治療他們的病因。

Our two next-generation correctors, VX-152 and VX-440 are being evaluated in Phase I studies in healthy volunteers. Pending data from these studies, we expect to move into Phase II clinical development in the second half of 2016 in people with CF. These studies would evaluate one or both of our next-generation correctors with VX-661 and ivacaftor.

我們的兩款新一代矯正器 VX-152 和 VX-440 正在健康志願者中進行 I 期臨床試驗。根據這些研究的數據，我們預計將於 2016 年下半年進入 CF 患者的 II 期臨床開發階段。這些研究將使用 VX-661 和 ivacaftor 評估我們的一種或兩種下一代矯正器。

Beyond our CFTR modulators, we have entered into multiple strategic collaborations that broaden our ability to evaluate additional approaches to CF treatment that maybe complementary to CFTR modulation in the future. While the underlying technology and science of each approach differs, the collaborations have a shared goal, to develop the best possible future treatments for all people with CF.

除了我們的 CFTR 調節劑之外，我們還開展了多項策略合作，這擴大了我們評估其他 CF 治療方法的能力，這些方法未來可能與 CFTR 調節劑互補。雖然每種方法的基本技術和科學原理各不相同，但這些合作有一個共同的目標，那就是為所有囊性纖維化患者開發出未來最好的治療方法。

Earlier this month, we entered into a collaboration with Moderna Therapeutics aimed at using messenger RNA to potentially enable cells in the lungs of people with CF to produce functional CFTR protein. This is the second platform technology collaboration we have entered into, following our agreement with CRISPR Therapeutics, focused on use of CRISPR-Cas9 for gene editing, that we began in late 2015. These platform technologies add to our development stage collaboration with Parion Sciences, focused on the use of ENaC inhibition to treat CF.

本月初，我們與 Moderna Therapeutics 展開合作，旨在利用信使 RNA 使囊性纖維化患者肺部的細胞能夠產生功能性 CFTR 蛋白。這是繼我們與 CRISPR Therapeutics 達成協議（專注於使用 CRISPR-Cas9 進行基因編輯）之後，我們進行的第二個平台技術合作。該協議於 2015 年底開始實施。這些平台技術為我們與 Parion Sciences 的開發階段合作增添了助力，該合作專注於利用 ENaC 抑制劑治療 CF。

As we enter the second half of 2016, I'm pleased with both the near and long-term growth opportunities for our business. Our goal is to consistently discover and deliver transformative new medicines for patients, and to reinvest in scientific opportunities to create future medicine. We believe our business model, which is focused on significant investment to create value through innovation, research and development will position us to achieve this goal over the coming years. With that, I'll turn the call over to Ian.

進入 2016 年下半年，我對我們業務的近期和長期成長機會都感到滿意。我們的目標是不斷發現並為患者提供變革性的新藥，並將資金再投資於科學機遇，以創造未來的藥物。我們相信，我們以大量投資為核心，透過創新、研發創造價值的商業模式，將使我們能夠在未來幾年實現這一目標。接下來，我將把電話交給伊恩。

Thanks Jeff, and hello, everyone. Through the second quarter of the year, we have created a growing revenue base with ORKAMBI and KALYDECO, which we expect to drive future earnings growth. Tonight, I'll discuss our second-quarter revenues for ORKAMBI and KALYDECO, review our 2016 financial guidance, and discuss our anticipated financial trajectory for the coming years.

謝謝傑夫，大家好。今年第二季度，我們透過 ORKAMBI 和 KALYDECO 建立了不斷增長的收入基礎，我們預計這將推動未來的獲利成長。今晚，我將討論 ORKAMBI 和 KALYDECO 第二季度的收入情況，回顧我們 2016 年的財務預期，並討論我們未來幾年的預期財務軌跡。

In the second quarter of 2016, we reported total CF product revenues of approximately $426 million, a significant increase compared to $155 million for the second quarter of last year. Turning to the revenues for each of our CF medicines, global sales of ORKAMBI in the second quarter were $245 million, comprised of US Sales of approximately $229 million, and ex-US sales of approximately $16 million, which were mainly from Germany. As of June 30, approximately 6,000 patients have initiated treatment with ORKAMBI in the US.

2016 年第二季度，我們報告的 CF 產品總收入約為 4.26 億美元，與去年第二季度的 1.55 億美元相比，實現了顯著成長。再來看我們每種 CF 藥物的收入，ORKAMBI 第二季的全球銷售額為 2.45 億美元，其中美國銷售額約為 2.29 億美元，美國以外地區的銷售額約為 1,600 萬美元，主要來自德國。截至 6 月 30 日，美國已有約 6,000 名患者開始接受 ORKAMBI 治療。

Outside the US, ORKAMBI is already available commercially in Germany and also through early access programs in France. In Germany, uptake continues to be slower than we observed in the US. As of June 30, approximately 380 of 2,500 eligible patients in Germany had initiated treatment.

在美國以外，ORKAMBI 已在德國上市銷售，並在法國透過早期訪問計劃提供。在德國，普及速度仍然比我們在美國觀察到的速度慢。截至 6 月 30 日，德國 2500 名符合條件的患者中約有 380 人已開始接受治療。

In contrast, in France, we have continued to see strong and rapid uptake. Approximately 700 of 1,500 eligible patients in France have already initiated treatment with ORKAMBI as of June 30, as part of the country's early access programs. These programs provided the opportunity for physicians in France to begin treating patients prior to their formal reimbursement approval.

相比之下，在法國，我們持續看到強勁快速的接受度。截至 6 月 30 日，法國 1500 名符合資格的患者中約有 700 人已經開始接受 ORKAMBI 治療，這是該國早期准入計畫的一部分。這些計畫為法國的醫生提供了在正式獲得報銷批准之前就開始治療病人的機會。

We are pleased the ORKAMBI launch has continued to progress, consistent with what we discussed on our first-quarter call. And today, we are reiterating our expectations for 2016 ORKAMBI revenues of $1 billion to $1.1 billion. Given the slower than expected launch in Germany, and that we're approaching peak penetration for ORKAMBI in patients aged 12 and older in the US, we expect the further revenue growth for ORKAMBI will occur primarily in the fourth quarter, following the potential approval and launch of ORKAMBI for children ages 6 to 11.

我們很高興 ORKAMBI 的發布工作繼續取得進展，這與我們在第一季電話會議上討論的內容一致。今天，我們重申我們對 ORKAMBI 2016 年營收的預期，即 10 億美元至 11 億美元。鑑於 ORKAMBI 在德國的上市速度比預期要慢，並且我們在美國 12 歲及以上患者中的 ORKAMBI 滲透率已接近峰值，我們預計 ORKAMBI 的進一步收入增長將主要發生在第四季度，屆時 ORKAMBI 將有望獲得批准並上市用於 6 至 11 歲的兒童。

Now to KALYDECO. Second-quarter KALYDECO sales were $180 million, up $25 million compared to the second quarter of last year. We continue to see a small number of additional eligible patients beginning treatment in US and Europe.

接下來是 KALYDECO。KALYDECO 第二季銷售額為 1.8 億美元，比去年第二季成長了 2,500 萬美元。我們看到美國和歐洲又有少量符合條件的患者開始接受治療。

As with ORKAMBI, we are reiterating our 2016 revenue guidance for KALYDECO of $685 million to $705 million. Our 2016 guidance excludes any potential revenues for the approval of KALYDECO in residual function mutations, where we continue to pursue the FDA approval for patients ages 2 and older in US.

與 ORKAMBI 一樣，我們重申對 KALYDECO 2016 年的營收預期為 6.85 億美元至 7.05 億美元。我們 2016 年的業績預期不包括 KALYDECO 在殘餘功能突變方面的獲批可能帶來的任何收入，我們將繼續尋求 FDA 批准其用於美國 2 歲及以上患者。

Now to the operating expenses. Our second-quarter non-GAAP operating expenses were $306 million, compared to non-GAAP operating expenses of $254 million in 2015. The increased operating expenses were mainly due to increased costs related to the progression of our CF pipeline, and to increased investment in global commercial support for the launch of ORKAMBI. Our non-GAAP net profit for the second quarter of 2016 was $58 million or $0.24 per diluted share, as compared to a non-GAAP net loss of $131 million or $0.54 per share for 2015.

接下來是營運費用。我們第二季的非GAAP營運費用為3.06億美元，而2015年的非GAAP營運費用為2.54億美元。營運費用增加主要是由於與 CF 產品線推進相關的成本增加，以及為 ORKAMBI 的上市而增加的全球商業支援投資。2016 年第二季度，我們的非 GAAP 淨利為 5,800 萬美元，即每股攤薄收益 0.24 美元，而 2015 年的非 GAAP 淨虧損為 1.31 億美元，即每股虧損 0.54 美元。

From a balance sheet perspective, we ended the second quarter with approximately $1.07 billion in cash, cash equivalents, and marketable securities. Vertex also has $300 million outstanding from a credit agreement, repayable by the end of the third quarter 2017.

從資產負債表的角度來看，我們在第二季末擁有約 10.7 億美元的現金、現金等價物和有價證券。Vertex 還有 3 億美元的未償還信貸協議款項，應於 2017 年第三季末償還。

I will conclude tonight's call with a few brief comments on financial trends, including revenue and earnings growth. Our goal is to discover and develop new medicines for all people with CF.

今晚的電話會議最後，我將簡要談談財務趨勢，包括收入和獲利成長。我們的目標是為所有囊性纖維化患者發現和開發新藥。

As Jeff has discussed, there are three important phases to support these efforts. Obtaining reimbursement for ORKAMBI outside the US, expanding labels for both ORKAMBI and KALYDECO, and developing new medicine to treat potentially all people with CF. As we progress towards this goal, significant and sustainable revenue growth will follow.

正如傑夫所討論的，支持這些努力有三個重要階段。在美國以外地區獲得 ORKAMBI 的報銷，擴大 ORKAMBI 和 KALYDECO 的適應症，並開發新藥物以治療所有可能患有 CF 的人。隨著我們朝著這個目標不斷前進，收入將實現顯著且可持續的成長。

Importantly, as our revenues grow over future years, we are committed to managing our operating expenses to drive earnings growth. We expect to deliver a financial profile that is similar to many of our large cap biotech peers. With that, I open the line to questions.

重要的是，隨著未來幾年收入的成長，我們將致力於控制營運費用，以推動獲利成長。我們預計財務狀況將與許多大型生技同業公司類似。接下來，我開始接受提問。

(Operator Instructions)

（操作說明）

Geoff Meacham, Barclays.

巴克萊銀行的傑夫·米查姆。

I have a few commercial ones, and one clinical. I wanted to ask you, either Ian or Stuart, any changes to the persistence rates in the US? What are the new strategies to improve it? And then can you just go into a little bit more detail on the EU outlook? From what I understand, being flattish in 3Q from Germany, and then maybe what's driving the fourth quarter bump?

我有一些商用設備，還有一台臨床設備。我想問伊恩或斯圖爾特，美國的保單持續率有任何變化嗎？有哪些新的策略可以改進它？那麼，您能否更詳細地談談歐盟的前景？據我了解，德國市場第三季表現平平，那麼是什麼因素推動了第四季的成長呢？

Geoff, it's Stuart here. So on persistence rates, what we're seeing in US is very consistent with what we outlined in our Q1 call. In fact, all of the trends, really in initiations, persistence and compliance, are entirely in line with what we said then.

傑夫，我是史都華。因此，就續約率而言，我們在美國看到的情況與我們在第一季電話會議中概述的情況非常一致。事實上，所有趨勢，包括發起、堅持和遵守情況，都與我們當時所說的完全一致。

Just to remind you and others on the phone, for persistence, we said our expectation was it would track towards about 70% to 80%, between 70% and 80% by the end of this year, and the same for compliance. And we continue to believe in those estimates, and those estimates are what underpins our revenue guidance that we reiterated today.

再次提醒您和其他電話那頭的人，關於堅持率，我們預計到今年年底將達到 70% 到 80%，合規率也是如此。我們仍然相信這些預測，而這些預測正是我們今天重申的收入預期的基礎。

In terms of Europe and as you know, the Germany uptake is relatively slow, Ian mentioned that in his prepared remarks. Incorporated within our guidance, really we're only expecting significant contributions ex-US from Germany. In terms of how we see things playing out in the rest of Europe, really as you know, that's going to be very dependent on us proceeding through the country by country reimbursement negotiation processes, and what I can tell you is that those are progressing as we planned, as expected.

就歐洲而言，正如你所知，德國的接受度相對較低，伊恩在他的準備好的演講稿中提到了這一點。根據我們的指導方針，我們實際上只期望德國（美國以外）做出重大貢獻。至於我們看到歐洲其他地區的情況會如何發展，正如你所知，這很大程度上取決於我們能否逐個國家地推進補償談判進程，我可以告訴你的是，這些談判正在按計劃進行，正如預期的那樣。

But given our learnings and the analogy to KALYDECO, and the time it took there, we're really not anticipating to conclude many of those reimbursement negotiations until 2017. Having said that, we recently concluded our first formal reimbursement negotiation in Austria, and now we're going to affect from September 1, but we continue to believe that most of the major markets, we're not likely to see any major contributions in terms of revenue growth until 2017 and beyond.

但鑑於我們從中學到的教訓，以及與 KALYDECO 的類似情況，還有當時所花費的時間，我們預計要到 2017 年才能完成許多報銷談判。儘管如此，我們最近在奧地利完成了首次正式報銷談判，現在我們將從 9 月 1 日起生效，但我們仍然認為，在大多數主要市場，我們不太可能在 2017 年及以後看到收入成長方面的任何重大貢獻。

Okay, and just real quick on the clinical side, I know it's less interesting, but the PK for 152 and 440, will we see any of that in any CF, and any more thoughts on what the size and scope of the critical development for the triple could entail? Thanks.

好的，關於臨床方面，我只想快速問一下，我知道這不太有趣，但是 152 和 440 的藥物動力學，我們會在任何囊性纖維化患者中看到這些嗎？關於三聯療法關鍵研發的規模和範圍，還有什麼其他想法嗎？謝謝。

Little difficult to answer that, to be honest, Jeff, to say the size of the triple -- if I comment more broadly on our operating expense for the remainder of the year, and then maybe the trajectory in 2017, that's an easy way for me to comment on it. We always plan and provide guidance based on assuming success, and therefore we are investing behind the programs. So our OpEx guidance for the year is at $1.18 billion to $1.23 billion, and we reiterated that number in the press release tonight. And that's a non-GAAP number by the way, excludes primarily stock compensation.

說實話，傑夫，這個問題有點難回答，要說三倍的規模——如果我更廣泛地評論一下我們今年剩餘時間的運營支出，以及2017年的發展軌跡，那對我來說就很容易評論了。我們始終以成功為前提進行規劃和指導，因此我們對這些項目進行了大量投資。因此，我們今年的營運支出預期為 11.8 億美元至 12.3 億美元，我們在今晚的新聞稿中重申了這一數字。順便一提，這是非GAAP數據，主要不包括股票補償。

And then as we look into next year, we actually see, we hope and expect the programs to progress. As we look into next year, as we think about OpEx more broadly, we see the maybe some marginal increases in marketing investments for the launch of ORKAMBI more broadly, and particularly in Europe as we get reimbursement approval. And as we look at development investment, maybe it's more consistent 2015 to 2016, as programs cycle in and out, with the expectation that the 661 Phase III program comes to closure and we are filing next year, and the progression of the triple into a larger Phase II study. So that gives you an understanding of the trajectory of our investment profile through this year and into next year.

展望明年，我們希望並期待各項計劃能夠取得進展。展望明年，當我們更廣泛地考慮營運支出時，我們看到，隨著 ORKAMBI 的更廣泛推廣，尤其是在歐洲獲得報銷批准後，行銷投資可能會略有增加。當我們審視研發投資時，或許 2015 年至 2016 年的情況會更加穩定，因為計畫會不斷輪換，預計 661 III 期計畫將結束，我們將在明年提交申請，而三重試驗將推進到更大的 II 期研究。這樣，您就可以了解我們今年及明年的投資組合走勢。

Geoff, this is Jeff Leiden, with respect to your question on the PK and what we have said before that will let you know as we conclude the Phase I studies and plan the Phase II studies, for the next-gen correctors, what those Phase II studies will look like, and we'll provide you with some relevant data, so you understand the design of those studies.

Geoff，我是 Jeff Leiden，關於你提出的藥物動力學問題，以及我們之前說過的內容，我們會在完成 I 期研究併計劃下一代矯正器的 II 期研究時，告訴你 II 期研究的具體內容，並向你提供一些相關數據，以便你了解這些研究的設計。

Okay.

好的。

As I said, are on track for the second half of this year.

正如我所說，我們正按計劃推進今年下半年的工作。

Okay, thanks.

好的，謝謝。

Michael Yee, RBC Capital Markets.

Michael Yee，加拿大皇家銀行資本市場。

Two questions as well. On the commercial side, are you based on the long-term data for ORKAMBI, are you starting to see any patients, perhaps thinking about coming back? Are there discussions out there in the field about bringing some patients back on, and what do you think about that standpoint? And then, a follow-up question on the triple. Is it safe to say that you have gone well into Phase I and the longer the better, and is there something specific in terms of exposure levels that you're looking for, relative to assays? That we could get some comfort in terms of what you want to see exposure decrease?

還有兩個問題。在商業方面，您是否基於 ORKAMBI 的長期數據，開始看到一些患者，或許正在考慮回歸？目前業界是否有關於讓部分病患重返治療的討論？您對此有何看法？然後，還有一個關於三重奏的後續問題。可以說你們已經順利進入 I 期臨床試驗階段，而且試驗時間越長越好。相對於檢測方法，你們在暴露程度方面是否有特定的要求？我們能否就您希望減少的暴露程度獲得一些安慰？

It's Jeff Chodakewitz. Let me touch on both of those for you. I think from the long-term data perspective, we think that is very meaningful to patients and to prescribers. I think the reasons for that our several-fold.

他是傑夫·喬達克維茨。讓我來為你簡單談談這兩點。我認為從長期數據的角度來看，這對患者和處方醫生來說都意義重大。我認為原因有很多。

As you know, that information really has a couple of chunks to it. One is about the long-term safety of the drug, which is very important, and that continues to look very favorable, consistent with what we've seen before. And then we have several more efficacy kind of measures. Some of that came from the study itself, we are following patients for a long time that we saw that their FEV1s were maintained, their PMI continued to improve, and although there's no active comparison there, the event rate in terms of pulmonary excavation really remained low, and consistent with what we saw during the trials. So that was very impactful we think for physicians and for patients.

如你所知，這些資訊實際上包含幾個部分。一是藥物的長期安全性，這一點非常重要，而且目前看來情況仍然非常樂觀，與我們之前看到的情況一致。此外，我們還有幾種其他的療效評估指標。其中一些結果來自研究本身，我們對患者進行了長期隨訪，發現他們的 FEV1 得以維持，PMI 持續改善，雖然沒有進行積極的比較，但肺泡擴張事件的發生率確實很低，與我們在試驗中看到的情況一致。所以我們認為這對醫生和病人都產生了非常大的影響。

The other thing we did was take the information from a matched cohort of historical patients, and what that allows you to do over that timeframe is to compare the rate of decline of patients FEV1s who are on our study versus what we think the historical expectation would be. And that really, then, as we did with KALYDECO, helps us understand if we are shifting that curve, and slowing the rate of decline, really modifying the disease. And we were very pleased to see that approximately 40% reduction in the rate of decline. So overall we think that data is very impactful and useful.

我們做的另一件事是，從一組匹配的歷史患者隊列中獲取信息，這樣就可以在一段時間內比較我們研究中患者的 FEV1 下降率與我們認為的歷史預期值。這樣一來，就像我們用 KALYDECO 所做的那樣，就能幫助我們了解我們是否正在改變這條曲線，減緩下降速度，真正改變這種疾病。我們非常高興地看到，下降速度降低了約 40%。總的來說，我們認為數據非常重要且有用。

In terms of triple combination, really can't give you a lot of details. As Jeff Leiden said actually already, that both drugs do continue in Phase I studies, and our expectation of course, pending data, is that one or both of those will start in patients for the second half of this year.

關於三連組合，真的無法提供太多細節。正如 Jeff Leiden 之前所說，這兩種藥物仍在進行 I 期研究，當然，根據數據，我們預計其中一種或兩種藥物將於今年下半年開始在患者身上進行試驗。

Okay, thanks.

好的，謝謝。

Geoffrey Porges, Leerink Partners.

Geoffrey Porges，Leerink Partners。

Question for Stuart. Perhaps I think about the PDUFA date and the pediatric indication for ORKAMBI. Could you talk about what pace you expect reimbursement to be available to the pediatric patients, the homozygous double deltas? And then secondly, as you are out in community and talking to physicians, do you think that the adoption, compliance, and persistence rates in the pediatric population will be similar to the adult population, or greater or less than you've observed so far? Thanks.

問史都華一個問題。或許我會考慮 ORKAMBI 的 PDUFA 日期和兒科適應症。您能否談談您預計兒科患者（純合雙δ基因突變患者）的報銷進度？其次，當您在社區與醫生交談時，您認為兒科人群的採納率、依從率和堅持率會與成人人群相似，還是會高於或低於您目前觀察到的情況？謝謝。

Yes, thanks for the question. So the PDUFA date is September 30, and obviously we're deep into the planning for that launch, it's certainly just a couple of months away. In terms of what we might anticipate for access, to answer the first part of your question, my expectation is that access is going to be very good, just as it was for ORKAMBI when we first introduced it for the 12 and over population, and in some ways, this is a somewhat simpler review for the payers, as it's today a label extension, just extending it down to a younger age. And so my expectation is that we will secure broad access very quickly.

是的，謝謝你的提問。PDUFA 日期是 9 月 30 日，顯然我們正在深入規劃此次發布，距離發布肯定只有幾個月的時間了。就我們預期的准入情況而言，回答你問題的第一部分，我預計准入情況會非常好，就像我們最初為 12 歲及以上人群推出 ORKAMBI 時一樣。在某些方面，這對支付方來說審查起來也稍微簡單一些，因為今天只是標籤擴展，將其適用年齡擴展到更年輕的人群。因此，我預計我們將很快獲得廣泛的訪問權限。

In terms of rate of uptake, similarly, I would anticipate the demand to be robust, just as it was for 12-plus, and in terms of persistence and compliance, again it's difficult to say exactly how it's going to play out in the real world, as opposed what we saw the clinical trial setting, but certainly a couple of things that I think are -- give us some encouragement. We certainly saw in the study that we did that forms the basis of our application that the adverse event rate, in particular the rates of respiratory adverse events was much lower and none of the patients discontinued for adverse events, and as you know, that's been one of the primary reasons for discontinuations on ORKAMBI in the 12 and over population.

就接受率而言，同樣，我預計需求會很強勁，就像 12 歲以上人群的需求一樣。至於堅持性和依從性，同樣很難說它在現實世界中會如何發展，與我們在臨床試驗環境中看到的情況不同，但肯定有兩件事——讓我們感到鼓舞。我們在我們所做的研究中確實看到，不良事件發生率，特別是呼吸系統不良事件發生率要低得多，而且沒有患者因不良事件而停止治療，正如您所知，這是 12 歲及以上人群停止使用 ORKAMBI 的主要原因之一。

And then again one thing that could help us, the 6 to 11 population certainly with KALYDECO, we do tend to see compliance rates being much higher in the younger populations, not surprisingly, as they tend to be very heavily managed by their parents and so while I don't know exactly how it's going to play out in the real world, certainly expect access be very good, to adopt quickly, and I'd also expect the uptake to be very rapid, as well.

還有一點可能對我們有幫助，那就是對於 6 至 11 歲的兒童來說，使用 KALYDECO 肯定比一般兒童更有利。我們發現，在年齡較小的群體中，依從率往往較高，這並不奇怪，因為他們往往受到父母的嚴格管控。雖然我不知道在現實世界中會如何發展，但我預計它的普及率會非常高，兒童很快就會接受它，而且我也預期它的推廣速度會非常快。

Thanks very much.

非常感謝。

Geoff, I'll just add onto Stuart to reiterate something I said in my comments, which is that Q4 is where we anticipate to see the growth in ORKAMBI for the remainder of the year, and obviously that is 6 to 11 that Stuart was just discussing.

Geoff，我只想補充Stuart的觀點，重申一下我在評論中說過的話，那就是我們預計ORKAMBI在今年剩餘時間裡的增長將出現在第四季度，顯然就是Stuart剛才討論的6到11個季度。

Great, thanks again.

太好了，再次感謝。

Brian Abrahams, Jefferies.

Brian Abrahams，傑富瑞集團。

As you see more uptake in Germany, and more patient going on treatment in France, I was wondering if you could talk a little bit about persistence and compliance patterns that you're starting to see in Europe? Could you expect to be able to leverage your learnings from the US launch, plus the availability of the long-term data now, to improve that patient retention in the European launches compared to the US? And then separately, just wondering if you could give us a little more granularity on the next steps, and your level of confidence on residual function mutations, where you stand there with the next regulatory steps? Thanks.

隨著德國接受治療的患者人數增加，以及法國接受治療的患者人數增多，我想知道您能否談談您在歐洲開始觀察到的治療堅持性和依從性模式？您能否利用從美國上市中汲取的經驗，以及現在可用的長期數據，來提高歐洲上市的患者留存率，使其高於美國？另外，我想單獨問一下，您能否更詳細地說明下一步的步驟，以及您對殘餘功能突變的信心程度，以及您對下一步監管措施的立場？謝謝。

Brian, I'll start off on the persistence and compliance and how things are playing out in Europe. One of the benefits of launching in Europe after launching here in the US is clearly we have been able to learn a lot from our experiences here in the US. And I think one of the things that we've been able to do is certainly sensitize people to the fact that some patients may have these respiratory adverse events, and so to be on the lookout, to be counseling patients in advance. And that has certainly has been one of the many learnings that we took from our experiences here in the US to the introduction of the product in Europe.

布萊恩，我先從堅持和合規性以及歐洲的情況說起。在美國推出產品後，在歐洲推出產品的好處之一是，我們顯然能夠從我們在美國的經驗中學到很多東西。我認為我們所做的一件事，就是讓人們意識到有些患者可能會出現這些呼吸系統不良事件，因此要保持警惕，並提前為患者提供諮詢。這無疑是我們從美國的經驗中汲取的產品引入歐洲過程中的眾多教訓之一。

The data sources are not quite as robust as we have here in the US, in terms of tracking at a non-biased level individual patient data in Europe, and I would say it's relatively early stage. The persistence rates are certainly in line, in the same ballpark as we saw with ORKAMBI here in the US. And as that data matures over time, we will be able to give you more detail on exactly how it's playing out. But at the minute, the data is relatively immature, I'd say it's pretty much in the same ballpark for persistence and compliance.

就追蹤歐洲個體患者數據而言，歐洲的數據來源不如美國那麼強大，而且我認為它還處於相對早期的階段。持續率確實符合預期，與我們在美國看到的 ORKAMBI 的情況大致相同。隨著數據的不斷完善，我們將能夠為您提供更多關於事態發展細節的資訊。但就目前而言，數據還相對不成熟，我認為在持久性和合規性方面，兩者基本上處於同一水平。

And Brian, this is Jeff Chodakewitz. Just to comment on residual function, we really can't comment, we have ongoing discussions with regulatory agencies. The only thing I can say is that we do really think all the data, both the preclinical data and the clinical data, really tells us that this drug is beneficial to those patients. And our goal is to figure out a way to get access for those patients.

布萊恩，這位是傑夫喬達克維茨。關於殘餘功能，我們實在無法置評，我們正在與監管機構進行討論。我唯一能說的是，我們確實認為所有數據，包括臨床前數據和臨床數據，都顯示這種藥物對這些患者是有益的。我們的目標是找到讓這些患者獲得治療的方法。

Thanks very much.

非常感謝。

Terence Flynn, Goldman Sachs.

特倫斯·弗林，高盛集團。

Maybe just two for me. First on ORKAMBI in the US, it looks like new patient adds have moderated somewhat this quarter, and I know you were talking about nearing peak. So is 6,000-ish what you were expecting now, or you think you can get to the rest of the 8,500 total?

或許我只需要兩個。首先是美國的 ORKAMBI，本季新增患者數量似乎有所放緩，我知道您之前說過患者數量接近高峰。所以，你現在預期可以達到 6000 左右嗎？還是你認為你能達到總共 8500 的剩餘部分？

And then in Germany versus France, obviously a difference in uptake. Just wondering what you think is driving that, and which other countries you could think about those patterns playing out? Are they going to be more like Germany or more like France? Thank you.

然後，德國和法國之間的接受程度顯然存在差異。我只是想知道你認為是什麼原因導致了這種情況，以及你認為還有哪些國家也出現了類似的模式？他們會更像德國還是更像法國？謝謝。

I'll start with the US, so as you said, with ORKAMBI, we've now initiated over 6,000 patients here in the US, which about 70% of the eligible patient population. And as you might expect with a launch we're getting to a steeper part of the curve, adding new patients becomes a little bit more tricky. Having said that, we are continuing to add new patients on a weekly and daily basis, but as Ian said in his prepared remarks, in terms of US growth, obviously the next phase in growth in the US like to be from the approval in 6 to 11, which we hope will come in the next couple of months.

我先從美國說起，正如您所說，ORKAMBI 目前已在美國為 6000 多名患者啟動治療，約佔符合條件的患者總數的 70%。正如你所預料的那樣，隨著產品上市，我們進入了曲線更陡峭的部分，增加新患者變得有點棘手。儘管如此，我們每周和每天都在繼續增加新患者，但正如伊恩在準備好的發言稿中所說，就美國的增長而言，顯然美國下一階段的增長可能要等到 6 到 11 年的批准之後，我們希望這將在未來幾個月內實現。

So moving on to how things are panning out in Europe, you're right, there is a contrast in uptake between Germany and France. Germany is slower than we anticipated, and much of that I attribute to the fact that the German market is more fragmented than many of the other markets that we operate in. What I mean by that is there's many more centers treating CF patients, and as a result, they've had less experience with CFTR regulators, and therefore the educational need is higher there. And also we did see a slightly slower uptake for KALYDECO in Germany than we saw in other EU markets.

那麼，接下來談談歐洲的情況，你說得對，德國和法國的接受度確實有差異。德國市場的成長速度比我們預期的要慢，我認為這主要是因為德國市場比我們經營的其他許多市場更加分散。我的意思是，現在治療囊性纖維化患者的中心更多了，因此，他們對 CFTR 調節劑的經驗較少，因此，他們的教育需求也更高。此外，我們也發現 KALYDECO 在德國的普及速度比在其他歐盟市場略慢。

Contrast that with France where through early access programs, we have -- 700 patients have already been initiated on ORKAMBI and that uptake in six months is much more US-like. So based on that, based on all the other research we've done, we do anticipate that Germany is more likely to be an outlier in terms of rates of uptake, although I continue believe that we will get to the vast majority of patients in Germany over time. In terms of rate of uptake, I would expect to be more like France in the rest of Europe, pending reimbursement, than we've seen in Germany, which I continue to believe is likely to be more of the outlier, based on our previous experience with KALYDECO and current experience with ORKAMBI.

相較之下，法國透過早期准入計劃，已經讓 700 名患者開始接受 ORKAMBI 治療，六個月內的接受度與美國的情況更為相似。因此，基於此，基於我們所做的所有其他研究，我們預計德國在普及率方面更有可能成為一個例外，儘管我仍然相信，隨著時間的推移，我們將涵蓋德國絕大多數患者。就普及率而言，我預計在報銷到位之前，歐洲其他地區的情況會更像法國，而不是像德國那樣。根據我們之前使用 KALYDECO 的經驗和目前使用 ORKAMBI 的經驗，我仍然認為德國的情況可能更像一個例外。

Great, thanks so much.

太好了，非常感謝。

Mark Schoenebaum, Evercore ISI.

Mark Schoenebaum，Evercore ISI。

This is John Miller on for Mark, and I just wanted to ask a question about this 6,000 patients that are started on ORKAMBI. You said those are starts, but what's the current number of patients on therapy? I'd love to know that. And my other question, I suppose, would be your thoughts on pricing pressure, especially in an orphan disease like this, where pricing ability has typically been very high. How do you look at that going forward, as that's obviously an issue?

這裡是約翰‧米勒，我替馬克提問，我想問一個關於這6,000名開始接受ORKAMBI治療的病患的問題。你說這些只是個開始，但目前接受治療的患者人數是多少？我很想知道。我想，我的另一個問題應該是您對價格壓力的看法，尤其是在這種罕見疾病領域，因為定價能力通常非常高。您如何看待這個問題的未來發展？這顯然是一個問題。

So I'll just reiterate what Ian said. In terms of the actual number of patients being treated, that's clearly a very dynamic number and changes constantly. So what we have said is that we have to date initiated 6,000 patients. We continue to see more initiations, and we continue to believe, as we did at the end of Q1, that the persistence rate of that patient population is going to be somewhere in the 70% to 80% range, as indeed we believe the compliance rate will be somewhere in the 70% to 80% range.

所以我只需重複一下伊恩所說的話。就實際接受治療的患者人數而言，這顯然是一個非常動態的數字，並且一直在變化。所以我們已經說過，到目前為止，我們已經為 6000 名患者啟動了治療。我們持續看到更多的新用戶加入，我們仍然相信，正如我們在第一季末所做的那樣，該患者群體的持續率將在 70% 到 80% 之間，事實上，我們相信依從率也將在 70% 到 80% 之間。

And so that's what we believe at the end of Q1. We continue to perform against those expectations, and that is the 12 and above patients in the US, is what underlies our revenue guidance that we reiterated today. In terms of pricing, clearly that's a very hot topic across the industry.

所以，這就是我們在第一季末的看法。我們繼續達到預期目標，而美國 12 例及以上患者的數量正是我們今天重申的收入預期的基礎。就定價而言，這顯然是整個行業非常熱門的話題。

We continue to believe that we are developing very high quality medicines, medicines that treat the underlying cause of what is a horrible life-shortening disease. It's for a very small patient population, and we believe and I think that's reinforced by the discussions we have had with government through the reimbursement of KALYDECO and the ongoing discussions we're having with ORKAMBI, this is exactly the sort of medicine that they want to be able to provide to their patient population. So whilst there will be pricing pressures because of the overall macroeconomics on every pharma and biotech company, I continue to believe the sort of agents we're bringing to bear are the sorts of products that governments are going to want to pay for.

我們仍然相信，我們正在研發非常高品質的藥物，這些藥物可以治療這種可怕的、縮短壽命的疾病的根本原因。它適用於非常小的患者群體，我們相信，而且我認為，我們與政府就 KALYDECO 的報銷問題進行的討論以及我們正在與 ORKAMBI 進行的討論也印證了這一點，這正是他們希望能夠為他們的患者群體提供的藥物類型。因此，儘管由於整體宏觀經濟形勢，每家製藥和生技公司都會面臨價格壓力，但我仍然相信，我們正在引進的這類藥物正是各國政府願意付費購買的產品。

Thank you very much.

非常感謝。

Matthew Harrison, Morgan Stanley.

馬修·哈里森，摩根士丹利。

This is Cyrus on for Matt. Couple of questions. First, are there any efforts to improve the persistence and compliance rates in the United States?

這是賽勒斯替馬特報道。我有幾個問題。首先，美國是否有任何措施來提高戒菸的持續性和依從性？

So yes, we have a number of programs, which are provided either through materials that we provide the healthcare providers, to provide to their patients, or where appropriate to provide directly to the patients, to educate them on the product, the mechanism of action, the fact that it treats the underlying nature of the disease. So these programs are ongoing, and I think an understanding and an educated patient is likely to be a more persistent and more compliant patient.

是的，我們有很多項目，這些項目要么通過我們向醫療保健提供者提供的材料，由他們提供給患者，要么在適當情況下直接提供給患者，以教育他們有關產品、作用機制以及它治療疾病根本性質的事實。所以這些計畫仍在進行中，我認為，理解並接受教育的患者更有可能成為更堅持治療、更配合治療的患者。

And also we continue to try and build the evidence-base for ORKAMBI, which increases the benefit risk profile, and to the extent that providers and patients continue to believe in the benefit risk profile, then I think they're going to want to try and maintain their time on the product, because of the both short and long-term benefits the treatment with ORKAMBI gives them.

此外，我們也持續努力為 ORKAMBI 建立證據基礎，以提高其獲益風險比。如果醫護人員和病人繼續相信其獲益風險比，那麼我認為他們會希望繼續使用該產品，因為 ORKAMBI 治療能為他們帶來短期和長期的益處。

Okay, and then the same question is, when will you would be able to recognize the revenues in France, and will they come as a lump sum, or how will it be dealt with?

好的，那麼同樣的問題是，您何時才能確認在法國的收入？這些收入會一次到賬，還是會分期處理？

Just to help everybody else, what's behind that question, we actually are providing access to ORKAMBI in France through early access programs and other programs, and we are actually being paid for that drug, and in my remarks, I did comment that launch in France is going very well, in that we're accessing a lot of patients. We do get a payment for that drug, that might be similar to how the ultimate price for the drug plays out in France.

為了幫助大家理解這個問題，我們實際上正在透過早期准入計劃和其他計劃在法國提供 ORKAMBI，並且我們實際上也獲得了該藥物的報酬。我在發言中也提到，該藥物在法國的上市進展非常順利，因為我們已經接觸到了許多患者。我們確實會收到這種藥物的報酬，這可能與這種藥物在法國的最終價格類似。

However, from a GAAP perspective, we are unable to record those -- access to those medicine as revenue until we have an agreed price in France. So I appreciate the question. We would anticipate that would be a 2017 event.

然而，從 GAAP 的角度來看，在我們與法國達成價格協議之前，我們無法將這些（獲得這些藥物）計入收入。我很感謝你的提問。我們預計這將是2017年的一件大事。

At the point that we do get approval on the price, which provides us certainty to reporting of those revenues, we actually record the revenue as one big catch-up. So as we've been selling drug since let's say January 1, 2016 all the way through the point of reimbursement approval, we will record that cash that we will have ultimately received as part of revenues in the quarter that we received reimbursement approval. We do think that would be a 2017 event

一旦價格獲得批准，我們就可以確定這些收入的申報，屆時我們實際上會將這筆收入記錄為一筆大的補錄收入。因此，假設我們從 2016 年 1 月 1 日開始銷售藥品，一直到獲得報銷批准為止，我們將把最終收到的現金計入獲得報銷批准的季度的收入中。我們認為那將是2017年的一場賽事。

Okay, great, thank you. And then last question. Is there any update to the 661 futility analysis timing for the heterozygous?

好的，太好了，謝謝。最後一個問題。661 無效性分析（針對雜合子）的時間安排有更新嗎？

It's Jeff Chodakewitz. I can tell you that as we've talked about previously, that is on track to occur during the third quarter, and then based upon that recommendation from the DMC, and remember we won't be seeing that information, we will either stop the study or restart enrollment and go to completion.

他是傑夫·喬達克維茨。我可以告訴你們，正如我們之前討論過的，這有望在第三季度實現，然後根據數據監測委員會的建議（記住，我們不會看到相關資訊），我們將停止這項研究，或者重新開始招募並完成研究。

Okay, thank you.

好的，謝謝。

Adam Walsh, Stifel.

Adam Walsh，Stifel。

My first one is, you talked about a large bolus of discontinuations in the first quarter because 15% of patients, I believe you cited, come off in the first three months. I just wondered if there was any residual bolus tail end into the second quarter. That's my first question, and then my second question is also on discontinuations.

我的第一個問題是，您提到第一季會出現大量停藥，因為我相信您引用過，15% 的患者在前三個月內就停止了治療。我只是想知道第二季是否還有殘留的胰島素劑量。這是我的第一個問題，我的第二個問題也是關於停產的。

You talk about the 15% in the first three months, and 20% to 30% longer-term. Can you help us, after the 15% dropout in the first three months, help us understand the discontinuation dynamics from that point to the 25% long-term discontinuation rate, which is the midpoint of your guidance?

您提到前三個月成長 15%，長期成長 20% 到 30%。在前三個月有 15% 的學員流失之後，您能否幫助我們了解從那時起到長期流失率達到 25%（這是您指導意見的中點）的流失動態？

So yes, thanks for the question. So yes, we did describe this bolus of discontinuations, and that was largely a function of two things. One, the very, very rapid uptake we saw of ORKAMBI post the initial launch, and then we did see about 15% of patients discontinue within the first three months of therapy, largely as the result of respiratory adverse events.

是的，謝謝你的提問。所以，是的，我們確實描述了這一波停產潮，這主要是由兩件事造成的。第一，ORKAMBI 在最初上市後獲得了非常非常迅速的推廣，然後我們看到大約 15% 的患者在治療的前三個月內停止治療，這主要是由於呼吸系統不良事件造成的。

And then what we saw was that the rate adverse, rate of discontinuations ameliorated substantially. It didn't stop, didn't flatten, but it certainly ameliorated substantially. And as a result of that, that's why we gave guidance that we see the discontinuations over the persistence rate, which is the opposite of the discontinuations being in that 70% to 80% range by the end of 2016. And everything we've seen through Q2 continues to reinforce our belief that's where we will end the year, somewhere in that 70% to 80% range. There wasn't really, if I understand your question correctly, there wasn't really a second bolus that negatively impacted Q2.

然後我們看到，不良事件發生率，即停工率，得到了顯著改善。它沒有停止，也沒有平息，但確實得到了極大的緩解。因此，我們給出的指導意見是，我們預計停用率將高於持續率，這與 2016 年底停用率達到 70% 至 80% 的預期相反。第二季的所有情況都進一步印證了我們的信念，那就是我們今年的最終完成率將在 70% 到 80% 之間。如果我理解你的問題沒錯的話，其實並沒有第二次注射會對 Q2 產生負面影響。

Great, I guess the question was, was there any tail end residual? You had the large number of patients start in the first nine months, and you said of that in the first quarter, as we moved into this quarter, was the bolus still moving through, in terms of the 15% discontinuations, or did that really end the first quarter?

太好了，我想問題是，是否存在任何尾部殘餘？前九個月有大量患者開始接受治療，您在第一季也提到這一點。進入本季後，15% 的停藥率是否仍持續，還是說第一季就此結束了？

Maybe a better way to answer this is that somebody asked us on the call earlier was that are we continuing to see the dynamics of the launch, and let's say the compliance rates and persistence rates. Are being maintained? And yes they are.

或許更好的回答方式是，之前有人在電話會議上問我們，是否繼續觀察產品發布的動態，例如合規率和持續率。是否正在維護？是的，他們確實是。

So when we talk about the profile of compliance with the medicines being between 70% and 80%, we're still seeing that. When we look at the persistence rate ending up at 70% to 80%, we're still seeing that, which means that every time there is a bolus of patients that is initiating therapy, we still continue to see discontinuations early on. However because these is a lower initiation of patients in Q1 or even the beginning of Q2, the impact of discontinuations in Q2 is much less than it has ever been.

所以，當我們談到藥物依從性在 70% 到 80% 之間時，我們仍然看到這種情況。當我們觀察持續率最終達到 70% 到 80% 的情況時，我們仍然看到這種情況，這意味著每次有大批患者開始接受治療時，我們仍然會看到早期中斷的情況。然而，由於第一季甚至第二季初的患者數量較少，第二季停藥的影響遠小於以往。

Perfect, thank you

太好了，謝謝。

Phil Nadeau, Cowen and Company.

Phil Nadeau，Cowen and Company。

Just a couple on the pipeline. So I guess first on VX-661's het-min futility analysis, you never disclosed exactly what the futility hurdle was. I was wondering whether you could give us some sense of the criteria, or at least how you're going to interpret a go signal in particular? And then a similar question on the Phase I for the second-generation correctors. Can you give us some idea of what criteria you are going to look at, to decide which will move forward, and do you have any plans to move other second-generation correctors into the clinic?

目前只有幾個項目正在籌備中。所以我想先在 VX-661 的 het-min 無效性分析中，你從未透露無效性障礙究竟是什麼。我想知道您能否為我們介紹評判標準，或者至少說明您將如何解讀「通過」訊號？然後，關於第二代矯正器的第一階段，也有類似的問題。您能否簡要說明您將參考哪些標準來決定哪些產品可以進入下一階段？您是否有計劃將其他第二代矯正器引入臨床？

It's Jeff Chodakewitz. In terms of 661's futility, I think, first of all, we really can't go into the details of exactly what the decision tree is, but let me help you think about it a little bit perhaps. There's a certain tension as you make a decision based on partial information. We want to try, if the drug is not benefiting patients, to stop the trial.

他是傑夫·喬達克維茨。關於 661 的徒勞性，我認為，首先，我們真的無法深入探討決策樹的具體細節，但或許我可以幫你稍微思考一下。根據不完整的資訊做出決定時，會產生一定的緊張感。如果該藥物對患者沒有益處，我們希望嘗試停止試驗。

Conversely, there is uncertainty, and we also want to be careful about not missing a positive result. Therefore there always is a certain overlap, and what we tend to do is then say it's clearly not working, we stop. The consequence of that is even if it goes forward, there is still uncertainty.

反之，也存在不確定性，我們也希望謹慎行事，不要錯過任何正面的結果。因此，總是會存在一定的重疊，而我們往往的做法是，當發現它顯然行不通時，我們就停止。結果是，即使專案得以推進，仍存在不確定性。

It does not mean that it's working, it just means that it may be working. And therefore until we get to these end of the study, we really would not have any confidence in what the result is going to be

這並不意味著它一定有效，只是意味著它可能有效。因此，在研究完成之前，我們對最終結果真的沒有任何信心。

Yes, and Jeff, before you go onto the next question, I would just comment from a disclosure perspective, we get asked this question a number of times. I want to be very clear on our disclosure around that, consisted of what Jeff was saying, if there is a discontinuation of the study due to the futility, we'll announce that the study is discontinuing, and that would be an appropriate announcement at the time that we get that information.

是的，傑夫，在你提出下一個問題之前，我想從資訊揭露的角度評論一下，我們經常被問到這個問題。我想非常明確地說明我們在這方面的披露，正如傑夫所說，如果由於無效而終止研究，我們將宣布研究終止，在我們獲得該資訊時，這將是一個合適的公告。

If we pass, no guarantees that it's working and therefore this drug, the information is submittable for approval. But the only way we communicate around that is on ClinicalTrials.gov, we will open the recruitment for that study, and we would expand the recruitment into the study, plus there wouldn't be an announcement saying that we passed the futility hurdle.

即使我們通過了測試，也不能保證它有效，因此，這種藥物的資訊可以提交審批。但我們只能透過 ClinicalTrials.gov 進行溝通，我們將開放該研究的招募，並將招募範圍擴大到該研究，而且不會發佈公告說我們已經克服了無效性障礙。

That's very helpful, thanks.

非常感謝，這很有幫助。

In terms of your other question, I think what we've always said is that what we want to do is bring these medicines, these compounds forward, but we want them to be medicines. So we try as much as possible to have drugs that we think can have a favorable profile in patients, so that they can continue. We're going to look at all the information, safety, exposure, all the things you would expect. There's really no one thing that I can say we're going to focus in on, it's really the totality of the profile of the drug.

至於你的另一個問題，我認為我們一直強調的是，我們想要推進這些藥物、這些化合物的研發，但我們希望它們成為真正的藥物。因此，我們盡可能選擇我們認為對患者有良好療效的藥物，以便他們能夠繼續接受治療。我們將查看所有資訊、安全、風險暴露情況，以及所有你期望看到的內容。我真的不能說我們會專注在哪一方面，而是要全面考慮藥物的各種特性。

Okay and do you have plans to move in any other second-generation correctors into the clinic, or is it really dependent on what you see in Phase I?

好的，你們是否有計劃將其他第二代矯正器引入臨床，還是這完全取決於你們在第一階段的試驗中看到的結果？

This is Jeff Leiden, thanks for the question. As we said before, this is a large program here. We have discovered a series of second-generation correctors, or next-generation correctors.

我是傑夫·萊頓，謝謝你的提問。正如我們之前所說，這是一個大型專案。我們發現了一系列第二代校正器，或者說是下一代校正器。

They have different flavors, which is interesting, and our strategy here is very straightforward: If we can develop a portfolio of products and bring some of those forward into the clinic and compare them, it gives us the best probability of success. So our plan is to continue that program in the research and pre-clinical phase, and if we see compounds that are interesting, good, better than the ones we have, we certainly will bring them forward into the clinic.

它們有不同的口味，這很有趣，而我們的策略非常直接：如果我們能夠開發一系列產品，並將其中一些產品推進到臨床進行比較，這將為我們帶來最大的成功機率。因此，我們的計劃是繼續推進該計畫的研究和臨床前階段，如果我們發現有趣、良好、比我們現有化合物更好的化合物，我們一定會將它們推進到臨床試驗階段。

Great, thanks for taking my questions.

太好了，謝謝你回答我的問題。

Alethia Young, Credit Suisse.

Alethia Young，瑞士信貸。

Just want to, 661 and the other study, can give us a flavor around maybe what the project is enrollment, not the homozygous but the other three studies? What sequence we might expect for the timelines? And the second one, just when you look at some of the long-term data that you generate on exacerbations like medical meetings by year, do you think that doctors are receiving that, patients are receiving that, that there is a very profound benefit, just saying ORKAMBI can be even somewhat similar to KALYDECO? Thanks.

我只是想問一下，661 和其他研究能否讓我們了解一下該計畫的招募情況，不是指純合子研究，而是指其他三項研究？時間軸可能會遵循怎樣的順序？第二個問題是，當你查看一些關於病情加重的長期數據，例如按年統計的醫療會議數量時，你認為醫生和患者是否從中受益匪淺，僅僅說 ORKAMBI 可能與 KALYDECO 有些相似？謝謝。

Sure, it's Jeff Chodakewitz. Let me first comment on the 661 sequence. First of all, as we indicated for the homozygous study, we have a lot of confidence in that, finishing enrollment in August, in fact, we've actually already stopped screening patients for that study, so it's just having the last patients completing the screening process and if they qualify, going into the trial.

沒錯，是傑夫·喬達克維茨。首先讓我評論一下661序列。首先，正如我們在純合子研究中指出的那樣，我們對此非常有信心，該研究已於 8 月完成招募，事實上，我們已經停止了該研究的患者篩選，現在只是讓最後幾位患者完成篩選過程，如果他們符合條件，就可以進入試驗。

We've already talked about the timing of the study of het-min patients and the futility analysis that's going to be done. We expect that the next trial that's going to be completed will be the study in patients with F508 on one allele and a residual function mutation on the other allele. And as we indicated, we expect that to complete in the second half of this year, very much as we indicated earlier this year, it's really right on track. And then the last study with F508 and gating on the other allele, again as we have indicated previously, we think the second half of this year or early next year, and as we get the data, that will allow us to evaluate our best submission strategy and file pending data in the second half of 2017.

我們已經討論過對異質性痢疾患者進行研究的時間安排以及將要進行的無效性分析。我們預計接下來要完成的試驗將是對一個等位基因攜帶 F508 突變，另一個等位基因攜帶殘餘功能突變的患者進行的研究。正如我們之前所說，我們預計該項目將在今年下半年完成，正如我們今年早些時候所說，目前一切都在按計劃進行。最後，我們將對 F508 進行研究，並對另一個等位基因進行門控。正如我們之前所指出的，我們認為這項研究將在今年下半年或明年年初進行，屆時我們將獲得數據，以便評估我們最佳的提交策略，並在 2017 年下半年提交待處理的數據。

In terms of the long-term data, I want to be sure that I understand your question. We do think that the results from that long-term data are quite compelling. You asked specifically about pulmonary exacerbations, and so we do look at what -- basically we use an assessment of how many events are happening for the patients that we're following, and think about it as an event rate.

關於長期數據，我想確認一下我是否理解了您的問題。我們認為，這些長期數據所得出的結果相當令人信服。您特別詢問了肺部急性惡化的情況，所以我們會觀察——基本上，我們會評估我們正在追蹤的患者中發生了多少次事件，並將其視為事件發生率。

And what we do see is that as we have gone out further in time, that remains quite low compared to what we had as our initial comparison. We think that is quite meaningful to patients and physicians, and actually that links up with the other information like body weight, and particularly the change in both FEV1, and evidence of disease modification, we think that is driving considerations like starting therapy earlier, and considering whether patients who have discontinued may want to think about restarting therapy.

我們看到，隨著時間的推移，這個數值仍然比我們最初的比較值要低得多。我們認為這對患者和醫生來說意義重大，而且實際上這與體重等其他信息，特別是 FEV1 的變化以及疾病改變的證據有關，我們認為這會影響到更早開始治療以及考慮已停止治療的患者是否應該考慮重新開始治療等因素。

Okay, thanks.

好的，謝謝。

Ying Huang, Bank of America.

黃穎，美國銀行。

Can you talk about maybe the ATU pricing you're getting in France, and how does that compare to the German pricing for ORKAMBI? And secondly also again on Europe, what's your thought on Brexit on the UK and also broadly speaking European reimbursement for ORKAMBI? Thanks.

您能否談談您在法國獲得的 ATU 定價，以及它與德國 ORKAMBI 的定價相比如何？其次，關於歐洲，您對英國脫歐以及歐洲對 ORKAMBI 的補償有何看法？謝謝。

So the ATU pricing in France has not been publicly disclosed, but it is very similar to the list price that we had established in Germany. In terms of the thoughts on the Brexit impact, certainly from a financial point of view in the short-term, the really most tangible impact that you can see is really one around the impact on FX, and because of the nature of our business and the natural hedges we have, we're not expecting that to have a meaningful impact on our business. There is obviously a range of other legal, regulatory, employment and other aspects that could be impacted by the Brexit, as the negotiations are ongoing. We're clearly going to be tracking those very closely, and making all the appropriate moves and responses as the situation becomes a situation becomes clear. But as with many things, Brexit, I think to speculate on too many other aspects of what the impact would be, would be crystal ball gazing at best.

因此，法國的 ATU 定價尚未公開披露，但它與我們在德國制定的價格非常相似。就英國脫歐的影響而言，從短期財務角度來看，最明顯的影響無疑是對外匯的影響。但由於我們業務的性質以及我們擁有的天然對沖手段，我們預期這不會對我們的業務產生實質的影響。顯然，由於談判仍在進行中，英國脫歐也可能對一系列其他法律、監管、就業和其他方面產生影響。我們顯然會密切注意這些情況，並隨著情況的發展採取一切適當的行動和應對措施。但就像很多事情一樣，我認為，對英國脫歐的其他方面可能產生的影響進行過多推測，充其量只是在做空。

And then maybe another one for Jeff. Could you tell us when might we see CRISPR and also the Moderna program getting to the clinic?

然後或許再給傑夫一個。您能否告訴我們，CRISPR技術和Moderna的基因編輯技術何時才能應用於臨床？

Thanks for the question. I appreciate you acknowledging the two very important collaborations we've actually done in the last year, standing up modalities we're getting from other diseases. But unfortunately, they are early stage, as you are probably aware, and we wouldn't anticipate getting anything to the clinic in the next couple of years. It's probably three years or more from now, and we would love to update you on that, but those have been important transactions for the Company.

謝謝你的提問。感謝您認可我們在過去一年中開展的兩項非常重要的合作，即建立我們從其他疾病中獲得的治療模式。但不幸的是，正如您可能已經了解的，它們還處於早期階段，我們預計在未來幾年內不會有任何產品進入臨床應用。可能還要三年或更久，我們很樂意屆時向您報告最新情況，但這些對公司來說都是重要的交易。

Thank you.

謝謝。

Liisa Bayko, JMP Securities.

Liisa Bayko，JMP Securities。

I thought you had a pretty good KALYDECO quarter. I'm just wondering if you comment on where, what's driving growth there? Is it from a particular region, or rolling out a new mutation?

我覺得你那張KALYDECO 25美分硬幣還挺不錯的。我只是想知道，如果您能就某個地區的情況發表評論，是什麼因素推動了那裡的成長？它是來自特定地區，還是正在傳播一種新的突變？

Liisa, thrilled with the question. It's nice to be able to talk about KALYDECO and thanks for noticing. Yes, KALYDECO had a very strong quarter of $180 million.

莉莎對這個問題欣喜若狂。很高興能有機會談論 KALYDECO，謝謝你的關注。是的，KALYDECO本季業績非常強勁，營收達1.8億美元。

Most of the growth over Q2 came from the US, and essentially what we continue to see is increasing new patient initiations in some of the newer indications, like the two five-year-old kids, and also in the R117H mutation. So we continue to see strong patient initiation, and as you know, the persistence rate and the compliance rates with KALYDECO are about as good as I've ever seen. So really, it's that combination of adding new patients and great persistence and compliance rates, particularly here in the US.

第二季度的大部分成長來自美國，我們持續看到的是，一些較新的適應症（如兩名五歲兒童）以及 R117H 突變的新患者數量不斷增加。因此，我們繼續看到患者積極參與治療，正如您所知，KALYDECO 的持續治療率和依從率是我見過的最好的。所以，關鍵在於增加新患者數量，以及較高的患者堅持率和依從性，尤其是在美國。

Okay, thank you for that. And then in terms of ex-US, is it -- just to make sure we're all on the same page, the only countries you're selling any drug, I mean distributing any drug to patients, I know you're not really selling in France per se, but France, Germany, and the US? Are those the totality of the countries?

好的，謝謝。那麼就美國以外的地區而言，為了確保我們理解一致，你們只向哪些國家銷售藥品，我是說要分發藥品給病人？我知道你們其實沒有在法國本土銷售，但法國、德國和美國呢？這些就是所有國家嗎？

So outside of the US, France and Germany are different from any of the other markets in that the way the structure of those markets work is that there are access programs that you can take advantage of, where patients can get access to the products prior to formal reimbursement approval being secured, on a relatively broad basis. And that's happening in both Germany and France, and Ian talked about the fact that within France, we never recognize those patients from a revenue perspective. In Germany, we do.

因此，在美國以外，法國和德國與其他任何市場都不同，因為這些市場的結構運作方式是，存在一些准入計劃，患者可以利用這些計劃，在獲得正式報銷批准之前，相對廣泛地獲得產品。這種情況在德國和法國都有發生，伊恩談到，在法國，我們從收入角度來看，從來不會承認這些病人。在德國，我們確實會這樣做。

There are other countries where on a named-patient basis, there are literally handfuls of patients who through exceptional programs are gaining access to the product, where we are getting paid. But the vast majority of our revenues outside of the US are coming from Germany. We expect that to continue in 2016, and we don't expect to get really meaningful revenue contributions from markets outside of Germany and outside of the US until 2017.

在其他一些國家，透過指定病人的方式，只有極少數病人透過特殊的項目獲得了該產品，我們也因此獲得了報酬。但除美國以外，我們的絕大部分收入都來自德國。我們預計這種情況將在 2016 年繼續，我們預計要到 2017 年才能從德國和美國以外的市場獲得真正有意義的收入貢獻。

Okay. I think that's it for me, thank you.

好的。我想我就說到這裡吧，謝謝。

Brian Skorney, Robert W. Baird.

布萊恩·斯科尼，羅伯特·W·貝爾德。

Two quick ones, I guess. First, can you just go over anything you've said about the differences between 152 and 440? Are they distinct corrective mechanisms?

我想應該是兩個簡短的問題吧。首先，您能否再回顧一下您之前提到的關於 152 和 440 之間差異的內容？它們是不同的糾正機制嗎？

I know you've always had the intention to move forward with both, but just wonder if there is a potential for these two drugs to actually complementary to each other, like 661 and lumacaftor, they're just overlapping? And then when we think about the peds approval later this year, do you think there is any meaningful numbers of peds patients currently on ORKAMBI off label, or do you think there is really a completely untapped patient pool right now?

我知道你一直打算同時推進這兩種藥物的研發，但我只是想知道這兩種藥物是否有可能像 661 和 lumacaftor 那樣相互補充，它們的作用機制只是重疊而已？那麼，當我們考慮今年稍後兒科用藥的批准時，您認為目前有多少兒科患者正在使用 ORKAMBI 的非適應症用藥，還是您認為目前真的存在一個完全未開發的患者群體？

Brian, it's Jeff Leiden. I'll take the first part, and then Stuart can take the second part. We haven't actually talked a lot in detail about mechanisms of action or the differences and or similarities between 152 and 440, but they're clearly molecules, and so that's what we have brought them both forward into the clinic.

布萊恩，我是傑夫萊頓。我來做第一部分，然後史都華可以做第二部分。我們其實還沒有詳細討論過 152 和 440 的作用機製或它們之間的異同，但它們顯然都是分子，所以我們才將它們都推進到了臨床階段。

What we have said is that we, as part of our discovery program, have discovered a portfolio of next-gen correctors which do have distinct mechanisms of action, as well as distinct drug-like properties. And that's why we're excited about the portfolio, and that's why we plan to take multiple molecules into the clinic, because at least in my experience, that's the way to maximize your chance of success.

我們已經說過，作為我們研發計畫的一部分，我們已經發現了一系列具有獨特作用機制和獨特藥物特性的下一代矯正劑。這就是為什麼我們對產品組合感到興奮，也是為什麼我們計劃將多種分子推進臨床試驗，因為至少以我的經驗來看，這是最大限度提高成功幾率的方法。

Brian on the off-label usage in the 6 to 11 population, we don't track off label usage, but my expectation is that it would be very, very low, and the reason why I say that is, the prior authorization for ORKAMBI, which enabled us to get very good access for ORKAMBI are very simple, but very clear, and then they would tend to say the person has to have a CF diagnosis, they have to have the right mutation type, and they check of the date of birth, they check the patient is 12 and above. So my expectation would be that the number of people receiving commercial products off label is going to be very, very low.

關於 6 至 11 歲族群的超適應症用藥問題，Brian 表示，我們不追蹤超適應症用藥情況，但我預期用藥量會非常非常低。我這樣說的原因是，ORKAMBI 的事先授權流程非常簡單明了，這使得我們能夠很好地獲得 ORKAMBI 的使用權。他們通常會說，患者必須被診斷出患有囊性纖維化，必須具有正確的突變類型，並且他們會檢查出生日期，還會檢查患者是否年滿 12 歲。因此，我預期非適應症用藥的人數將會非常非常少。

Great, thanks.

太好了，謝謝。

Operator, we will take two more questions before concluding the call.

接線員，在結束通話前，我們再回答兩個問題。

Katherine Xu, William Blair.

Katherine Xu，William Blair。

I'm just wondering with ORKAMBI versus KALYDECO, do you see a little bit lower compliance or persistence for ORKAMBI as compared to KALYDECO, and if that's the case, do you think it's mostly because of safety or lower efficacy or both? Any sense on that, at all?

我想問一下，與 KALYDECO 相比，ORKAMBI 的依從性或持續性是否略低於 KALYDECO？如果是這樣，您認為這主要是由於安全性較低還是療效較低，或者兩者兼而有之？對此有任何看法嗎？

Katherine, so with KALYDECO, we see very high levels of both persistence and compliance. We have said that our persistence with KALYDECO is 90%-plus, and overall compliance both here in the US and internationally is around 85%. And as we said at Q1 and is baked into our revenue guidance, we expect persistence for ORKAMBI to be between 70% and 80%, then for compliance to be in the same 70% to 80% range so we do see both of those criteria being lower for ORKAMBI than they are for KALYDECO. And to attribute exactly why that is, I'm not sure I would be able to tease that out for you. I'm sure it's got to do with the benefit risk and tolerability profile of ORKAMBI versus KALYDECO, but exactly which factor is weighting it one way or the other, I think would be impossible to differentiate.

Katherine，所以透過 KALYDECO，我們看到了非常高的堅持性和合規性。我們曾表示，我們對 KALYDECO 的堅持率超過 90%，在美國和國際上的整體合規率約為 85%。正如我們在第一季所說，也體現在我們的營收預期中，我們預期 ORKAMBI 的持續率將在 70% 到 80% 之間，合規率也將在同樣的 70% 到 80% 的範圍內，因此我們認為 ORKAMBI 的這兩個指標都低於 KALYDECO。至於具體原因，我恐怕也無法為你詳細解釋清楚。我確信這與 ORKAMBI 和 KALYDECO 的獲益風險和耐受性有關，但究竟是哪個因素起了決定性作用，我認為是無法區分的。

And could you give us a quick update on your oncology in teens pipeline candidates?

能否簡單介紹一下你們在青少年腫瘤治療領域的研發進展？

This is Jeff Chodakewitz, just give you a quick comment, and then maybe Jeff Leiden comment. In terms of our oncology program, I think very much consistent with where we were expecting it previously, that molecule, VX-970 is really in focused critical trials in very specific populations, and non-comparative trials to understand what the potential for that drug really can be, and so those are ongoing. On the pain side, our VX-150 actually just is finishing, has finished enrolling a Phase II POC study in osteoarthritis patients, and we expect to have some information later this year.

我是 Jeff Chodakewitz，我先簡單說幾句，然後 Jeff Leiden 也可能說幾句。就我們的腫瘤治療計畫而言，我認為與我們先前的預期非常一致，VX-970 分子目前正在針對特定族群進行重點關鍵試驗，以及進行非對照試驗，以了解該藥物的真正潛力，這些試驗正在進行中。在疼痛治療方面，我們的 VX-150 實際上剛剛完成，已經完成了一項針對骨關節炎患者的 II 期 POC 研究的招募工作，我們預計今年晚些時候會有一些資訊公佈。

So I would just pick up on that and say, because people ask us, are we going to be an oncology company, and I think that's a little early to suggest that, given that we have one lead molecule at the moment in early-stage studies in oncology. We're going to continue to progress our studies, as Jeff Chodakewitz said, and based on that data, we will make a choice at that time as to whether we provide further investment, or we actually look to see whether the mechanism is better served working with other companies, and therefore looking more of a portfolio approach to drive forward our oncology opportunities. We do have other mechanisms, one that is in the clinic, and then a couple that are just late pre-clinical right now. So we have a late pre-clinical couple of compounds, and also early clinical compounds, and that's where, in terms of our oncology portfolio, and we'll make the decision of how to progress that best for greatest value once we receive the data from VX-970, the lead program.

所以我會順便說一下，因為有人問我們，我們會不會成為一家腫瘤公司，我認為現在就這麼說還為時過早，因為我們目前只有一個主要分子處於腫瘤學的早期研究階段。正如 Jeff Chodakewitz 所說，我們將繼續推進我們的研究，並根據這些數據，屆時我們將決定是否提供進一步的投資，或者我們是否會考慮與其他公司合作，從而採取更多元化的投資組合方式來推進我們的腫瘤學機會。我們還有其他機制，其中一種已經進入臨床階段，還有幾種目前正處於臨床前研究的後期階段。因此，我們有一些處於臨床前後期階段的化合物，以及一些處於臨床早期階段的化合物，這就是我們腫瘤產品組合的現狀。一旦我們收到主要項目 VX-970 的數據，我們將決定如何以最佳方式推進這些項目，以實現最大價值。

Alan Carr, Needham & Company.

艾倫·卡爾，尼德姆公司。

A couple of them here. One of them, it looks like the only program we haven't touched on is 210. Wondering if you can give us an update on that in the spinal cord. And also with respect to your SNDA around residual mutations for KALYDECO, what sort of options do you have available here, in your discussions with FDA?

這裡有幾個。其中，看起來我們唯一還沒談到的程式是 210。想請您介紹一下脊髓方面的最新情況。另外，關於您針對 KALYDECO 殘留突變的 SNDA，您在與 FDA 的討論中有哪些選擇？

Jeff Chodakewitz. So Alan, I'd say first of all, in terms of VX-210, that study is up and enrolling. Frankly, we have had enrollment now in the trial, but these are acutely ill, acutely injured people so we have always expected that enrollment will be slow, and so we are really pretty much on track, in terms of residual function as we talked about earlier. There's really just nothing in terms of ongoing discussions with the regulatory agencies that I can talk about further.

傑夫·喬達克維茨。所以艾倫，首先我想說的是，就 VX-210 而言，這項研究已經啟動並開始招募受試者。坦白說，我們現在已經開始招募試驗對象，但這些都是病情危重、傷勢嚴重的患者，所以我們一直預計招募速度會比較慢，因此，就我們之前討論過的殘餘功能而言，我們實際上基本按計劃進行。就目前與監管機構的討論而言，我真的沒有什麼可以進一步談論的了。

Can you comment, I'm wondering if you comment on -- what the outcomes might be here, is this something that might be resolved this year, or does this potentially involve more studies? What can you comment from that perspective?

您能否就此發表一下看法？我想知道您對以下方面有何評論——此事可能會有哪些結果，是否有可能在今年得到解決，或者這是否可能需要更多的研究？從這個角度來看，您有什麼看法？

It's Jeff Leiden. So as you know, we just don't comment on ongoing regulatory discussions, partly because they are not predictable, and they are not totally within our control. I think the important point is we do believe that KALYDECO is active in this set of patients, based on both preclinical and clinical data, and we're having ongoing discussions with the regulator about how to get access to these patients with KALYDECO. When we have an answer, we'll certainly disclose that for you.

他是傑夫·萊頓。如您所知，我們不對正在進行的監管討論發表評論，部分原因是這些討論無法預測，而且也不完全在我們的控制範圍內。我認為重點是，根據臨床前和臨床數據，我們相信 KALYDECO 對這組患者有效，我們正在與監管機構就如何讓這些患者使用 KALYDECO 進行持續討論。一旦有了答案，我們一定會第一時間告訴您。

Fair enough, thanks very much.

好的，非常感謝。

Thank you. I'm showing no further questions at this time. I would like to turn the conference back over to Mr. Michael Partridge for any final remarks.

謝謝。我目前沒有其他問題要問。我謹將會議交還給麥可·帕特里奇先生，請他作最後的總結發言。

Okay, thanks operator. We appreciate everyone joining us tonight. We are happy to take additional follow-up questions after the call, and the Investor Relations team will be the office, so please reach out, and have a good night.

好的，謝謝接線生。感謝各位今晚的到來。通話結束後，我們很樂意回答其他後續問題，投資者關係團隊將在辦公室，請隨時聯繫我們，祝您晚安。

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

女士們、先生們，感謝各位參加今天的會議。今天的節目到此結束。你們可以斷開連結了。祝大家今天過得愉快。