福泰製藥 (VRTX) 2015 Q2 法說會逐字稿

Good evening, everyone. This is Michael Partridge, Head of Investor Relations for Vertex Pharmaceuticals. Welcome to our second-quarter 2015 financial results conference call.

各位晚安。我是 Vertex Pharmaceuticals 投資人關係主管 Michael Partridge。歡迎參加我們 2015 年第二季財務業績電話會議。

(Caller Instructions)

(來電者指示)

As a reminder, this conference call is being recorded, and a replay will be available following the conclusion of tonight's call on our website. Earlier in July, we announced the approval of ORKAMBI, and many of you joined for that call. Tonight, we will be focused on second-quarter performance and our execution against our corporate strategy. Joining me on tonight's call are Dr. Jeff Leiden, Chairman and CEO; Stuart Arbuckle, Chief Commercial Officer; and Ian Smith, Chief Financial Officer. Jeff Chodakewitz, our Chief Medical Officer, is traveling, and is not with us tonight.

提醒各位，本次電話會議將被錄音，並且在今晚電話會議結束後，可於我們網站上收聽重播。7 月稍早，我們宣布 ORKAMBI 獲得核准，許多各位也參加了那場電話會議。今晚我們將聚焦於第二季表現，以及我們依公司策略執行的進展。今晚與我一同參與電話會議的有：董事長兼執行長 Jeff Leiden 博士、商務長 Stuart Arbuckle，以及財務長 Ian Smith。我們的醫務長 Jeff Chodakewitz 正在出差，今晚無法出席。

Our agenda tonight is as follows: Jeff will begin by discussing key priorities for our business. Stuart will review the second-quarter performance of KALYDECO and make a few comments on the ORKAMBI launch, and to close, Ian will review the second-quarter 2015 financial results and update our 2015 guidance. You can access the webcast slides by going to the events section of the Investor Relations page on our website.

今晚議程如下：Jeff 將先談論我們業務的關鍵優先事項。Stuart 將回顧 KALYDECO 第二季表現，並就 ORKAMBI 上市推出發表幾點看法；最後，Ian 將回顧 2015 年第二季財務結果並更新我們 2015 年的財測指引。您可前往我們網站投資人關係頁面的活動（events）區，取得網路直播簡報投影片。

I will remind you that 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 (technical issue) without limitation those regarding the ongoing development and potential commercialization of ORKAMBI, those about Vertex's other cystic fibrosis programs, and Vertex's future financial performance are based on Management's current assumptions. Actual outcomes and events could differ materially.

我提醒各位，我們將在本次電話會議中作出前瞻性陳述。這些陳述受今日新聞稿與我們的 10-K 中所詳述之風險與不確定性影響，其中包括（技術問題）但不限於：關於 ORKAMBI 持續開發與潛在商業化的相關事項、關於 Vertex 其他囊性纖維化（CF）計畫的相關事項，以及關於 Vertex 未來財務表現的相關事項，皆係基於管理階層目前的假設。實際結果與事件可能出現重大差異。

Information regarding our use of GAAP and non-GAAP financial measures, and a reconciliation of GAAP to non-GAAP is available in our second-quarter 2015 financial results 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.

關於我們使用 GAAP 與非 GAAP 財務衡量指標的資訊，以及 GAAP 與非 GAAP 的調節表，已載於我們 2015 年第二季財務結果新聞稿中。我也請各位參考今晚網路直播的第 4 張投影片。接下來我把電話交給 Jeff Leiden 博士。

Thanks, Michael. Good evening, everyone. The approval of ORKAMBI on July 2 was an important milestone in our shared journey with the cystic fibrosis community. ORKAMBI is the first FDA-approved medicine to treat the underlying cause of CF for the approximately 8,500 people in the US 12 years and older with two copies of the F508del mutation. This is a big step forward toward our long-term vision of helping more people with CF. We feel very fortunate to be part of the CF community, and we appreciate all of the positive feedback we have received and continue to receive from patients, caregivers, healthcare providers, and the broader CF community.

謝謝你，Michael。各位晚安。ORKAMBI 於 7 月 2 日獲得核准，是我們與囊性纖維化社群共同旅程中的重要里程碑。ORKAMBI 是首個獲 FDA 核准、可治療囊性纖維化（CF）根本病因的藥物，適用於美國約 8,500 名、12 歲以上且帶有兩份 F508del 突變拷貝的患者。這是朝向我們長期願景、幫助更多 CF 患者的一大步。我們很榮幸能成為 CF 社群的一份子，也感謝我們從患者、照護者、醫療照護提供者以及更廣泛的 CF 社群所收到、並持續收到的所有正面回饋。

At the beginning of this year, we outlined three strategic priorities that will allow Vertex to continue to deliver on our vision to make new transformative medicines available to patients globally. Let me briefly review our progress toward meeting those goals. First, through both geographic and label expansion, we have continued to grow the number of patients treated with KALYDECO, resulting in strong revenue growth. With the ORKAMBI approval and launch in the US, we have an even greater opportunity to treat more patients, resulting in additional revenue growth.

在今年年初，我們提出三項策略優先事項，使 Vertex 能持續實現我們的願景：在全球讓患者取得全新、具變革性的藥物。我簡要回顧我們達成這些目標的進展。第一，透過地理區域擴張與適應症標籤（label）擴展，我們持續增加接受 KALYDECO 治療的患者人數，帶動強勁的營收成長。隨著 ORKAMBI 在美國獲准並上市，我們有更大的機會治療更多患者，進而帶來額外的營收成長。

Second, we know that there is still much more to do. We continue to make significant investment into multiple programs to create more CF medicines that may enable us to treat even more patients, and to improve the benefit for the patients we treat. All four studies included in the VX-661 plus ivacaftor pivotal Phase III development program are initiated, and we also remain on track to bring a next-generation CFTR corrector into the clinic by the end of 2015.

第二，我們知道仍有更多工作要做。我們持續對多項計畫進行重大投資，以開發更多 CF 藥物，讓我們能治療更多患者，並提升我們所治療患者的療效受益。VX-661 加 ivacaftor 的關鍵性第三期（pivotal Phase III）開發計畫所包含的四項研究均已啟動；同時，我們也仍按計畫在 2015 年底前將下一代 CFTR 校正劑（corrector）推進至臨床試驗。

And third, we have expanded and diversified our pipeline through our collaboration with Parion to develop and commercialize investigational epithelial sodium channel, or ENaC inhibitors, for CF and other pulmonary diseases. We also continue to advance early stage development programs outside of CF, including clinical programs in oncology, and research programs focused on other areas. We look forward to updating you on these programs later this year.

第三，我們透過與 Parion 的合作，擴大並多元化我們的研發管線，以開發並商業化用於 CF 與其他肺部疾病的研究性上皮鈉通道（epithelial sodium channel，ENaC）抑制劑。我們也持續推進 CF 以外的早期開發計畫，包括腫瘤領域的臨床計畫，以及聚焦於其他領域的研究計畫。我們期待在今年稍晚向各位更新這些計畫的進展。

The continued execution on our strategy has fundamentally changed the outlook for our business. Specifically, moving forward, we expect to deliver a financial profile of growing revenues, earnings, and cash flows, while also continuing to invest to create new medicines to treat more patients with CF and other serious diseases. With that, I'll hand it over to Stuart.

我們持續落實策略執行，已從根本上改變了公司業務的前景。具體而言，展望未來，我們預期將呈現營收、獲利與現金流持續成長的財務輪廓，同時也將持續投資，以創造新藥來治療更多 CF 患者及其他嚴重疾病患者。接下來我把電話交給 Stuart。

Thanks, Jeff, and hello, everyone. I will review KALYDECO performance in the second quarter, and also make a few comments regarding our progress in making ORKAMBI available to eligible patients in the US. Global sales of KALYDECO this quarter were $155 million, comprised of US sales of approximately $93 million, and ex-US sales of approximately $62 million. This represents a 37% increase compared to $113 million in the same quarter last year.

謝謝你，Jeff，各位好。我將回顧 KALYDECO 在第二季的表現，並就我們在美國讓符合資格的患者取得 ORKAMBI 的進展發表幾點看法。本季 KALYDECO 全球銷售額為 1.55 億美元，其中美國銷售約 9,300 萬美元，美國以外地區銷售約 6,200 萬美元。相較去年同季的 1.13 億美元，成長 37%。

The strong growth of KALYDECO is a result of both geographic and label expansion. We have seen good uptake in patients with the R117H mutation, following approval in the US in late 2014, and in children ages 2 to 5 with eligible mutations, following US approval at the end of March 2015. Internationally, there has also been rapid uptake of KALYDECO by eligible patients in Australia, following the reimbursement agreement reached in late 2014.

KALYDECO 的強勁成長來自地理區域擴張與適應症標籤（label）擴展。在 2014 年底於美國獲准後，我們看到帶有 R117H 突變的患者採用情況良好；而在 2015 年 3 月底於美國獲准後，具符合條件突變的 2 至 5 歲兒童患者也呈現良好採用。在國際市場方面，隨著 2014 年底達成給付（reimbursement）協議後，澳洲符合資格的患者也迅速採用 KALYDECO。

Also during the second quarter, we achieved reimbursement approval for non-G551D gating mutations in several European countries, where these mutations are prevalent, including Italy, France, England, and the Netherlands. As a result, today more than 85% of eligible gating patients in Europe now have access to KALYDECO. Further growth in patients receiving KALYDECO will be tempered by enrollment in the VX-661 pivotal program, as previously described, and this is reflected in our KALYDECO revenue guidance.

此外，在第二季期間，我們也在數個歐洲國家取得非 G551D 閘控（gating）突變的給付核准；這些國家此類突變較為常見，包括義大利、法國、英格蘭與荷蘭。因此，目前歐洲超過 85% 符合資格的閘控突變患者已可取得 KALYDECO。如先前所述，因患者納入 VX-661 關鍵性計畫（pivotal program），接受 KALYDECO 治療的患者人數進一步成長將受到抑制；此點亦已反映在我們對 KALYDECO 營收的財測指引中。

Now, turning to ORKAMBI, since the FDA approval of ORKAMBI on July 2, we have been working to get the medicine to the approximately 8,500 eligible patients as rapidly as possible. Our field teams around the country have been educating healthcare providers on the ORKAMBI prescribing information. Since approval, they have visited the vast majority of the 275 CF centers in the US. As we anticipated, interest in the medicine is very high.

接著談 ORKAMBI，自 7 月 2 日 ORKAMBI 獲 FDA 核准以來，我們一直努力以最快速度將藥物提供給約 8,500 名符合資格的患者。我們遍布全國的外勤團隊一直在向醫療照護提供者說明 ORKAMBI 的處方資訊。自核准以來，他們已拜訪美國 275 家 CF 中心中的絕大多數。如我們所預期，市場對該藥物的興趣非常高。

We believe that all eligible patients with CF should have access to ORKAMBI. Our public and private payer interactions to date have been productive, and our patient support team has begun to help patients navigate the reimbursement process. Thanks to these efforts and the commitment of healthcare providers at CF centers across the country, I am happy to report that the first patients are already receiving ORKAMBI in the US.

我們相信，所有符合資格的囊性纖維化（CF）患者都應該能夠取得 ORKAMBI。迄今為止，我們與公私部門支付方的互動都很有成效，而我們的病患支援團隊也已開始協助病患了解並完成給付報銷流程。得益於這些努力，以及全國各地 CF 中心醫療照護提供者的投入，我很高興地報告，美國已有首批患者正在接受 ORKAMBI 治療。

In summary, geographic and label expansion continued to drive significant growth in the number of patients we treat with KALYDECO, and with the launch of ORKAMBI, we are significantly expanding the number of eligible CF patients we treat. I'll now hand the call over to Ian.

總結而言，適應症標籤與地域擴張持續推動我們以 KALYDECO 治療的患者人數顯著成長；隨著 ORKAMBI 的上市，我們正大幅擴大可接受治療的 CF 合格患者人數。接下來我把電話交給 Ian。

Thanks, Stuart, and good evening, everyone. Tonight, I would like to discuss our second-quarter 2015 financial results, and then update our 2015 financial guidance. Firstly, to the financials. KALYDECO revenues were $155 million this quarter and were up 37% from the second quarter of 2014, and up 18% sequentially compared to our first quarter this year. We continued to nicely expand the number of eligible patients we treat with KALYDECO.

謝謝你，Stuart，各位晚安。今晚我想討論我們 2015 年第二季的財務結果，並更新我們 2015 年的財務指引。首先談財務數字。本季 KALYDECO 營收為 1.55 億美元，較 2014 年第二季成長 37%，較今年第一季亦季增 18%。我們持續穩健擴大以 KALYDECO 治療的合格患者人數。

Our second quarter non-GAAP R&D and SG&A expenses were $254 million, an increase of $17 million compared to last year, mainly due to an increase in SG&A expenses supporting the launch of ORKAMBI. Our non-GAAP net loss was $131 million compared to prior-year non-GAAP net loss of $142 million. From a balance sheet perspective, we maintained a strong position with approximately $1 billion of cash at the end of the quarter.

我們第二季非 GAAP 研發（R&D）與銷售、一般及行政（SG&A）費用為 2.54 億美元，較去年增加 1,700 萬美元，主要因為為支援 ORKAMBI 上市而增加的 SG&A 費用。我們的非 GAAP 淨損為 1.31 億美元，去年同期非 GAAP 淨損為 1.42 億美元。從資產負債表角度來看，我們維持強勁部位，季末現金約 10 億美元。

Let's now turn to the 2015 financial guidance, and specifically KALYDECO revenues and combined R&D and SG&A expenses. Earlier this year, we anticipated 2015 KALYDECO revenues to be between $560 million and $580 million. Based on an increased uptake due to label and geographic expansions that Stuart previously mentioned, we now expect KALYDECO net revenues to be between $575 million and $590 million for the full year 2015. For the non-GAAP operating expenses, we continue to expect the combined non-GAAP R&D and SG&A expense to be between $1.05 billion and $1.1 billion for the full year. I would just note that we expect our operating expense to be higher in the second half of this year compared to the first half, mainly as a result of the anticipated progress with the VX-661 pivotal program and the investment to support the launch of ORKAMBI.

接下來談 2015 年財務指引，特別是 KALYDECO 營收以及合計的研發與 SG&A 費用。今年稍早，我們預期 2015 年 KALYDECO 營收介於 5.60 億至 5.80 億美元。基於 Stuart 先前提到的適應症標籤與地域擴張帶來更高的採用率，我們現在預期 2015 全年 KALYDECO 淨營收介於 5.75 億至 5.90 億美元。就非 GAAP 營業費用而言，我們仍預期全年合計非 GAAP 研發與 SG&A 費用介於 10.5 億至 11 億美元。我想補充的是，我們預期今年下半年營業費用將高於上半年，主要是因 VX-661 關鍵性（pivotal）計畫預期進展，以及為支援 ORKAMBI 上市所做的投資。

I will close by stating that we are in a strong financial position today. We are growing our revenues, and we expect to show additional growth from ORKAMBI. We will continue to invest to create even more medicines and support access to those medicines already approved.

最後我想說，我們目前的財務狀況非常穩健。我們的營收正在成長，並預期 ORKAMBI 將帶來額外成長。我們將持續投資，以創造更多藥物，並支持已獲核准藥物的可近性。

With that, I'll ask the operator to please open the line for questions.

接下來，我請接線員開放提問。

(Operator Instructions)

（接線員指示）

Michael Yee, RBC Capital Markets.

Michael Yee，RBC Capital Markets。

Congrats on all the progress. A question for Stuart and a question for Ian. Stuart, appreciate the comments on the launch. Maybe you could just comment on more specifically on reimbursement and the process for reimbursement that you're seeing. Are payers quickly getting people on drug? Maybe walk us through that process and how long it takes to get people on drug that you're seeing out there.

恭喜各項進展。我有一個問題問 Stuart，另一個問題問 Ian。Stuart，感謝你對上市的評論。也許你可以更具體談談你們目前看到的給付報銷以及報銷流程。支付方是否很快就讓病人用上藥？能否帶我們走一遍你們看到的流程，以及讓病人開始用藥大概需要多久？

And then for Ian, I know you maintained the guidance for expenses, which is fantastic. I know people are thinking bigger picture, as you transform into a very profitable company. Maybe you can comment about how R&D expenses, how you're thinking about -- they're giving you now an ENaC inhibitor -- you've got all of these Phase IIIs, how are you thinking about controlling some of that or making sure we're going be very profitable? Thanks.

然後給 Ian，我知道你維持了費用指引，這很棒。我知道大家在想更長期的圖景，因為你們正轉型成一家非常獲利的公司。也許你可以談談研發費用：你們現在有一個 ENaC 抑制劑，還有這麼多第三期試驗，你們如何思考控制這些支出，或確保我們會非常獲利？謝謝。

Mike, it's Stuart. Thanks for the question. So in terms of the process for reimbursement, essentially, payers fall into a couple different camps. Some come to making formal decisions very quickly, and we've seen some of those. Most have a process where they are going to have the equivalent of a PNT committee and review the product. And those will often then put in interim policies, as it were, where they will evaluate on a case by case basis, whether a patient can be initiated on ORKAMBI.

Mike，我是 Stuart。謝謝你的問題。就報銷流程而言，支付方基本上可分成幾種不同類型。有些會很快做出正式決策，我們也確實看到一些這樣的案例。多數支付方有一套流程，會由相當於 PNT 委員會的機制來審查該產品。而他們通常會先制定臨時政策，也就是逐案評估患者是否可以開始使用 ORKAMBI。

So as a result of those interim policies and some initial policy decisions, that's why we have already seen patients start on ORKAMBI in the first few weeks following launch. Over the next few months, more and more payers will come to their final determinations on their coverage policies for ORKAMBI. As I say, based on the discussions we've had so far, we do continue to anticipate that we are going to have broad and positive reimbursement for ORKAMBI. And I'll pass it over to Ian to handle the expenses question.

因此，正是因為這些臨時政策以及一些初步的政策決定，我們才會在上市後的前幾週就已看到患者開始使用 ORKAMBI。在接下來幾個月，會有越來越多支付方對 ORKAMBI 的給付涵蓋政策做出最終決定。如我所說，根據我們迄今的討論，我們仍預期 ORKAMBI 將獲得廣泛且正面的報銷支持。我把問題交給 Ian 來回答費用方面。

Mike, thanks for the question. I'm going to take a little broader, if you don't mind, really comment on what is our goal with, let's say the Vertex financial profile. It starts with a growing revenue stream, which we are very confident around, given the recent approval of ORKAMBI. We looked at growing that rapidly, providing access to the medicines that are already approved, and basically holding at a steady state our operating expenses in the Company.

Mike，謝謝你的問題。如果你不介意，我想從更宏觀的角度來談，真正評論一下我們對 Vertex 財務輪廓的目標是什麼。這從持續成長的營收來源開始；鑑於 ORKAMBI 最近獲得核准，我們對此非常有信心。我們著眼於快速擴大營收、讓已獲核准的藥物能被取得，同時基本上將公司的營業費用維持在穩定水準。

The primary driver within our operating expense structure is R&D. That's a function of our commercial model as we get -- provide access to the medicines around the world, which is highly leveraged with small investment required to provide access to these medicines. Actually, providing access to the medicines is more about education than it is about selling a drug.

在我們的營業費用結構中，最主要的驅動因素是研發。這也與我們的商業模式有關：當我們在全球推動藥物可近性時，這是一個高度槓桿化的模式，只需要相對小的投資就能讓這些藥物被取得。事實上，推動藥物可近性更多是教育問題，而不是銷售藥品。

So that allows us, as a business, to reinvest in R&D, yet still aim to have high operating margins. And as we see out over the next three or four years, we do see ourselves as a business that if we can drive our medicines to patients and hold our operating expense, which is exactly what we expect, that we generate high operating margins, and operating margins that are consistent with, let's say, larger-cap biotech peers.

因此，這讓我們作為一家企業，能夠再投資於研發，同時仍以高營業利益率為目標。展望未來三到四年，我們確實認為，只要我們能把藥物送達患者並維持營業費用穩定——這正是我們所預期的——我們就能產生高營業利益率，而且其水準將與較大型市值的生技同業一致。

Perfect. Thank you very much.

很好。非常感謝。

Geoff Meacham, Barclays.

Geoff Meacham，巴克萊。

Thanks for taking the question, and good quarter. A couple more clinical questions. I'm hoping somebody there can answer it, but I noticed in the press release today one of the end points for the younger population in Europe, the 6 to 11, was absolute change in lung clearance. I wasn't sure if you were rethinking some of the end points overall for development beyond FEV1, or is this just a special case, just given the age of the population? I have a couple of other pipeline questions as follow-up.

感謝讓我提問，本季表現不錯。我還有幾個臨床方面的問題。希望在座有人能回答：我注意到今天的新聞稿中，歐洲較年輕族群（6 到 11 歲）的其中一個終點是肺清除的絕對變化。我不確定你們是否正在重新思考整體開發上、超越 FEV1 的一些終點，還是這只是特殊情況，主要是因為受試族群的年齡？我還有幾個其他管線問題想接著追問。

Geoff, this is Jeff Leiden. Jeff Chodakewitz is traveling today so he's not here, so I'm going to take the R&D questions. Thanks for asking that question. We've been talking for some time, both with Wall Street and with regulators, about the notion that we are eager to explore additional end points to FEV1, particularly for younger populations, where it's more difficult to consistently blow a good FEV1, if you're two or three years old. As part of that, we've explored three or four different end points, including lung clearance index.

Geoff，我是 Jeff Leiden。Jeff Chodakewitz 今天在出差不在，所以由我來回答研發相關問題。謝謝你提出這個問題。我們一段時間以來一直在和華爾街以及監管機構討論：我們很希望探索 FEV1 以外的其他終點，特別是對較年幼的族群，因為如果只有兩、三歲，要穩定地吹出良好的 FEV1 更困難。作為其中一部分，我們已探索三到四種不同的終點，包括肺清除指數。

And this was a very nice opportunity in talking with European regulators about this younger population, to begin to use lung clearance index, which is much less effort-dependent, and much more consistent, particularly in young patients as an efficacy end point. It will be interesting to see the result of this study, which we think will be highly predictive, using this end point. And we also plan to use those kinds of results to begin to discuss with other regulators whether these other end points might be useful, particularly in the young, very young patients.

而這次與歐洲監管機構就這個較年輕族群進行討論，是一個很好的機會，開始使用肺清除指數；它對受試者努力程度的依賴更低、結果更一致，特別適合作為年幼患者的療效終點。這項研究使用該終點的結果將很值得關注；我們認為它會具有高度預測性。我們也計畫利用這類結果，開始與其他監管機構討論：這些其他終點是否可能有用，尤其是在年輕、非常年幼的患者中。

Okay. That's helpful, Jeff. And another question, on the ENaC inhibitor, does this change the priorities for you, for your next-gen corrector, or would you view this as complementary to what you already have? And are we still on track to identify the third corrector by, I guess, by year end, early part of next year? Thanks.

好的。這很有幫助，Jeff。另外一個問題，關於 ENaC 抑制劑：這是否會改變你們對下一代校正劑的優先順序，還是你們會把它視為與既有方案互補？另外，我們是否仍按計畫在我想是今年底、或明年初辨識出第三個校正劑？謝謝。

Maybe I'll take those in reverse order, Geoff. Yes, we're absolutely on track to identify the third corrector. And just to remind you, I know you know this, but our strategy here has been to bring multiple next-gen correctors into the clinic, and our goal was the first one by the end of this year with several others following directly behind it. That's progressing nicely, and we are on track.

Geoff，也許我倒過來回答。是的，我們完全按計畫在辨識第三個校正劑。再提醒一下，我知道你也清楚：我們的策略是把多個下一代校正劑推進臨床，我們的目標是今年底前讓第一個進入臨床，並且有數個其他候選緊接著跟進。目前進展良好，我們仍在軌道上。

With respect to the ENaC inhibitors, we do view them very much as complementary. They could be complementary in a couple of ways, right? Because they fall outside of the classic CFTR correction, they may have activity as monotherapy, particularly in populations like [het-mins] that don't have anything, and frankly in other lung diseases as well. But we're particularly eager to study them on top of our current regimens, like ORKAMBI, because they may amplify the signal that we're seeing here.

至於 ENaC 抑制劑，我們確實將其視為高度互補。它們可能在幾個方面形成互補，對吧？因為它們不屬於典型的 CFTR 校正機制，可能作為單藥治療也有活性，特別是在像 [het-mins] 這類目前沒有任何治療選項的族群中，而且坦白說，在其他肺部疾病中也可能如此。但我們尤其希望在我們目前的治療方案（例如 ORKAMBI）之上研究它們，因為它們可能放大我們在此看到的訊號。

I wouldn't view them as one or the other. I would definitely view them as complementary. I guess your question is sort of getting at, do they in any way slow down or deprioritize our next-gen correctors, and the answer is no. We're full speed ahead on next-gen correctors.

我不會把它們視為二選一。我一定會把它們視為互補。我想你的問題是在問：它們是否會以任何方式放慢或降低我們對下一代校正劑的優先順序；答案是否定的。我們會全速推進下一代校正劑。

Okay. Great. Really helpful. Thanks.

好的。很好。非常有幫助。謝謝。

Matt Roden, UBS.

Matt Roden，瑞銀。

Thanks very much for taking the question. First, Stuart, I wonder if you could elaborate on some launch metrics that you're seeing. I know it's early days here, but is there any sense for the numbers of centers prescribing, or any other early indicators from maybe a time from prescription to fill? Any other metrics you can share, so we can get a sense of what's happening out there?

非常感謝讓我提問。首先，Stuart，我想請你進一步說明你們看到的一些上市指標。我知道現在還很早，但是否能掌握有多少中心開始開立處方，或其他早期指標，例如從開立處方到完成領藥的時間？還有其他你能分享的指標，讓我們了解外部的進展情況嗎？

And then I think this might be for Ian. If you could help us square the sales and the increase in guidance against your prior comments regarding the impact of enrollment of VX-661 trials on KALYDECO use. Do you have a same-store sales metric that enables you to see that impact is happening, but that the geographic expansion and label expansion is compensating for that, or is it just that it's actually not happening to the extent that you previously thought? That is the impact of 661 trials? Thanks very much.

接著我想這題可能要問 Ian。你能否協助我們釐清：銷售表現與上調財測指引，如何與你先前關於 VX-661 試驗收案對 KALYDECO 使用量影響的評論相互對照？你們是否有同店銷售（same-store sales）指標，能看出該影響確實正在發生，但地理擴張與適應症標籤擴張正在抵消它；還是其實影響並沒有如你們先前所想的那麼大？也就是 661 試驗的影響？非常感謝。

Matt, hi, it's Stuart here. Just in terms of launch metrics, we're less than four weeks in since the approval. So I'm really not going to comment on specific launch metrics and how predictive those are of the kind of trajectory that we are seeing overall. As we said before, because of the interest in the product, the unmet need, and the fact that it treats the underlying cause, we're certainly expecting the overall penetration of ORKAMBI in the eligible patient population to be high, and we've said all along that we do think though it will take longer for ORKAMBI to reach peak penetration compared to KALYDECO for a number of factors that we've gone into previously, like the volume of patients, and the time it's going to take to educate patients, and get them through the reimbursement approval process. But it's really much too early to be throwing around specific launch metrics right now. And then on the guidance and KALYDECO revenue question, I'll throw that over to Ian.

Matt，你好，我是 Stuart。就上市指標而言，自核准以來我們還不到四週。所以我不打算評論具體的上市指標，以及它們對我們整體所看到的成長軌跡有多大的預測性。如同我們先前所說，基於市場對產品的興趣、未被滿足的醫療需求，以及它能治療根本原因，我們確實預期 ORKAMBI 在符合資格患者族群中的整體滲透率會很高；我們也一直表示，相較於 KALYDECO，ORKAMBI 達到峰值滲透率可能需要更長時間，原因有多項我們之前已談過，例如患者人數規模，以及教育患者並讓其完成給付核准流程所需的時間。但現在談具體的上市指標仍然太早。至於指引與 KALYDECO 營收的問題，我把問題交給 Ian。

Matt, thanks for the question. I'll first start by saying we're very pleased with the expansion of KALYDECO, and treating more patients through geographic and label expansion. As far as the guidance we provided for the full year, we do actually now anticipate patients that would be available for the medicine, mainly in Europe actually, to go into the 661 trials. If you remember, ORKAMBI was approved in the US. We switched recruitment to the VX-661 pivotal studies back to Europe.

Matt，謝謝你的提問。我先說，我們對 KALYDECO 的擴張感到非常滿意，透過地理擴張與適應症標籤擴張來治療更多患者。就我們提供的全年指引而言，我們現在確實預期原本可能會使用該藥物的患者（主要其實是在歐洲）會進入 661 試驗。如果你記得，ORKAMBI 已在美國獲准。我們已將 VX-661 關鍵性研究的招募重心轉回歐洲。

Europe is where we're starting to continue to recruit new patients, potentially based on the label expansion of KALYDECO, and instead of going on to KALYDECO, we're starting to recruit those into our 661 studies. So we have built that into our guidance, and hence why we come out with something that is between $575 million and $590 million. Therefore, reflecting a lower growth rate than where we currently are between Q1 and Q2. We do think it will flatten out.

歐洲是我們開始持續招募新患者的地方，這些患者可能是基於 KALYDECO 的適應症標籤擴張而符合條件；但我們不是讓他們使用 KALYDECO，而是開始把他們招募進我們的 661 研究。因此我們已將這點納入指引，也就是為什麼我們給出的區間是 5.75 億至 5.90 億美元。因此，這反映出相較於目前 Q1 到 Q2 的成長速度，未來成長率會較低。我們確實認為它會趨於平緩。

Okay, great. Thanks for taking the question.

好的，很棒。謝謝讓我提問。

Geoffrey Porges, Bernstein.

Geoffrey Porges，Bernstein。

Congratulations on the progress and the good numbers. Question, first related to the extension study for the patients that were on ORKAMBI coming into the approval. Could you give us a sense of first, how many of the patients who were eligible were actually enrolled and stayed on treatment? And then what number of them have rolled over to commercial drug? And then I wanted a quick follow-up on VX-371. Jeff, perhaps you could discuss why do the study with ORKAMBI rather than with 661?

恭喜你們的進展以及亮眼的數字。第一個問題與針對在核准前就使用 ORKAMBI 的患者所做的延伸研究有關。能否請你們先讓我們了解一下，符合資格的患者中，實際有多少人入組並持續接受治療？接著，其中有多少人已轉換到商業用藥？然後我想就 VX-371 快速追問一下。Jeff，也許你可以談談，為什麼這項研究要搭配 ORKAMBI，而不是搭配 661？

So, Geoff, it's Stuart here. In terms of the number of patients who rolled over from TRAFFIC and TRANSPORT into the extension study, that number was very high. It was north of 90%, and Jeff Chodakewitz, if he were here, would have the exact numbers, but it was north of 90% of patients rolled over from TRAFFIC and TRANSPORT into the open label extension. About half of those were in the United States, and the process of informing those centers and those patients that the commercial product is now available and beginning to roll those patients over to commercial product is just beginning, but it's about 500 or so of the 1,000 who rolled over into the 105 study were here in the United States. And on the VX-371, I'll pitch back to Jeff Leiden.

Geoff，我是 Stuart。就從 TRAFFIC 與 TRANSPORT 轉入延伸研究的患者人數而言，比例非常高。超過 90%，如果 Jeff Chodakewitz 在場，他會有精確數字，但確實是超過 90% 的患者從 TRAFFIC 與 TRANSPORT 轉入開放標籤延伸研究。其中約一半在美國；目前正在開始通知這些中心與患者，商業化產品已可取得，並開始將這些患者轉換到商業化產品，但大約是 1,000 名轉入 105 研究的患者中，有約 500 名左右在美國。至於 VX-371，我把問題交回給 Jeff Leiden。

Geoff, in terms of VX-371 and why we're going with ORKAMBI, it's really a matter of how do we get the medicine potentially to patients the fastest. So since ORKAMBI is already approved, simply adding one unapproved drug and getting the result will let us, assuming that we have success, will let us get to, get that new drug, VX-371 to patients the quickest. Our goal all along has been improving therapy as quickly as we could.

Geoff，關於 VX-371 以及為什麼我們選擇搭配 ORKAMBI，主要是考量如何能讓藥物以最快速度可能提供給患者。由於 ORKAMBI 已經獲准，只要再加入一個尚未核准的藥物並取得結果，在假設成功的情況下，就能讓我們更快把這個新藥 VX-371 帶給患者。我們一路以來的目標就是盡可能快速地改善治療。

Okay. Thanks very much.

好的。非常感謝。

Terence Flynn, Goldman Sachs.

Terence Flynn，Goldman Sachs。

Thanks for taking the question. Maybe just two for me. Can you remind us about the anticipated timing of Medicaid coverage for ORKAMBI? And regarding the VX-661 KALYDECO trial in het-mins, now that you've started that trial, can you just maybe remind us of expectations for when that interim analysis might occur? Thank you.

謝謝讓我提問。我這邊可能兩個問題。能否提醒我們 ORKAMBI 的 Medicaid 給付預期時程？另外，關於 VX-661 與 KALYDECO 在 het-mins 的試驗，既然你們已經啟動該試驗，能否也提醒我們預期何時會進行期中分析？謝謝。

Yes, Terence, it's Stuart here. In terms of Medicaid coverage, there really isn't one answer. There's really 50 answers because, obviously, Medicaid is managed state by state. So I really can't give you one answer to the Medicaid question.

好的，Terence，我是 Stuart。就 Medicaid 給付而言，這其實沒有單一答案。實際上有 50 個答案，因為很明顯 Medicaid 是由各州分別管理。所以我無法對 Medicaid 的問題給出一個統一答案。

What I can share is that we've already seen patients initiated on therapy in the first four weeks, and within that number of patients, we have patients who have commercial insurance as their primary insurance. We also have patients who have government insurance, in the number of people who have already been initiated. But to give one specific number for Medicaid, it's just impractical because there's really 50 answers to that particular question. For the second part of the question, I'll hand it over to Jeff.

我可以分享的是，我們已經看到在前四週就有患者開始接受治療，而在這些已啟動治療的患者中，有些以商業保險作為主要保險。我們也有一些患者是政府保險，在已啟動治療的人數中也包含這類患者。但若要給出 Medicaid 的單一具體數字並不實際，因為這個問題確實有 50 個不同答案。至於問題的第二部分，我交給 Jeff。

In terms of the het-min trial, just to remind you, Terence, we actually just announced that trial is open for enrollment, so it's essentially starting now, if you want to think about it that way. To remind you the design of that trial, it actually has two parts. We enroll around 150 patients, plus or minus. We then have a DSMV that will do a futility analysis. We won't actually see the numbers at that point. They will simply tell us to stop if it's futile, or to continue.

關於 het-min 試驗，Terence，提醒你一下，我們其實才剛宣布該試驗已開放收案，所以如果你要這樣理解的話，它基本上現在才開始。再提醒你該試驗的設計，它其實分成兩個部分。我們會收案大約 150 名患者，上下浮動一些。接著會有 DSMV 進行無效性（futility）分析。在那個時間點我們其實不會看到數據。他們只會告訴我們若無效就停止，或是繼續進行。

If they tell us to continue, we then enroll another approximately 150 patients. Because of the shorter study than the 24-week homozygous study, we would still have visibility to that data by the time we had visibility to the homozygous study. We expect that to be sometime in 2016, depending on how quickly the enrollment goes. Does that answer your question?

如果他們告訴我們繼續，我們接著會再收案約 150 名患者。由於這項研究比 24 週的同型合子研究更短，即便如此，我們仍會在看到同型合子研究數據的同一時間點左右，對這項研究的數據有可見度。我們預期會在 2016 年的某個時間點，取決於收案速度。這樣有回答你的問題嗎？

Yes, thank you. And maybe Stuart, just one follow-up on Medicaid. Can you just remind us in terms of KALYDECO what the benchmark was there, in terms of -- I understand it's at a state level, but just what was the range in terms of how long the process took from the first date to the last date?

有，謝謝。另外 Stuart，關於 Medicaid 我再追問一下。能否提醒我們，以 KALYDECO 來看當時的基準是什麼——我理解是州層級，但從第一個州到最後一個州完成流程，所花時間的範圍大概是多少？

Well, it's splitting hairs a little bit there, Terence. The uptake with KALYDECO is so rapid. As you know, we got to 90%-plus percent of patients. We were at 90% of peak in six months. And so it was really incredibly rapid across both commercial payers and Medicaid. So there really wasn't much of a range that I could give you there. It was incredibly rapid for KALYDECO across all patient populations and all insurers.

Terence，這有點是在鑽牛角尖。KALYDECO 的採用速度非常快。如你所知，我們達到 90% 以上的患者覆蓋。我們在六個月內就達到峰值的 90%。因此不論是商業支付方還是 Medicaid，速度都非常快。所以我其實很難給你一個明顯的區間範圍。KALYDECO 在所有患者族群與所有保險別的推進都非常迅速。

Okay, thanks.

好的，謝謝。

Cory Kasimov, JPMorgan Chase.

Cory Kasimov，JPMorgan Chase。

I guess just to follow up on that, just based on your early discussion with payers on ORKAMBI, is there any change to your expectations for gross to net, or maybe another way, has the reaction to the price been about what you expected when you announced it earlier this month? And then secondly, on the new ENaC product you have, does the ongoing Phase II trial in patients with any CFTR mutation include heterozygous patients? Thanks.

我想就此追問一下，根據你們與支付方就 ORKAMBI 的早期討論，你們對毛到淨（gross to net）的預期有任何改變嗎？或者換個方式問，對於你們本月稍早公布價格後，市場對價格的反應是否大致符合你們的預期？第二個問題，關於你們新的 ENaC 產品，目前在任何 CFTR 突變患者中進行的第二期試驗，是否包含異型合子患者？謝謝。

Cory, on the reaction to the price, I would say has been very balanced, indeed, the focus of our discussions has really been less around the price and more around the clinical profile of ORKAMBI. And in terms of whether it changes our view on the gross to net, it really doesn't. The gross to net is almost exclusively driven by the payer mix, and as we have explained previously, we are expecting the Medicaid payer mix to be a higher percentage for ORKAMBI than it was for KALYDECO, and it's likely to be around that sort of 35% to 40% of eligible patients we predict will be covered by Medicaid. The vast majority of the rest will be covered by commercial insurance. Our view on that gross to net hasn't been changed by anything we've seen in the first four weeks.

Cory，關於對價格的反應，我會說確實相當平衡；事實上，我們討論的重點較少放在價格，而更多放在 ORKAMBI 的臨床特性。至於是否改變我們對毛到淨的看法，並沒有。毛到淨幾乎完全由支付方組合所驅動；如我們先前解釋過，我們預期 ORKAMBI 的 Medicaid 支付方占比會高於 KALYDECO，且我們預估符合資格患者中約有 35% 到 40% 會由 Medicaid 給付。其餘絕大多數將由商業保險給付。在前四週我們所看到的情況，並未改變我們對毛到淨的看法。

Okay, great.

好的，很棒。

And then in terms of the ENaC trial, just to remind you, they're actually -- we're planning two trials. The first one is already under way. That trial is basically monotherapy in any mutation. I assume you're referring to het-mins, and so the answer is yes, het-mins would be there, with the obvious exception that KALYDECO-treated patients, and now going forward, ORKAMBI-treated patients wouldn't be included in that study. The second study is going to be the ENaC inhibitor on top of ORKAMBI in patients who are treated with ORKAMBI.

接著就 ENaC 試驗而言，提醒您一下，我們其實——我們規劃了兩項試驗。第一項已經在進行中。那項試驗基本上是在任何突變類型下的單一療法。我想您指的是 het-mins，所以答案是肯定的，het-mins 會納入，當然有個明顯的例外：已接受 KALYDECO 治療的病人，以及接下來已接受 ORKAMBI 治療的病人，不會被納入該研究。第二項研究將是在已使用 ORKAMBI 治療的病人中，在 ORKAMBI 基礎上加用 ENaC 抑制劑。

Okay. Perfect. Thank you.

好的。完美。謝謝。

Ying Huang, Bank of America Merrill Lynch.

Ying Huang，美國銀行美林。

First one, maybe for Stuart, it was reported that the Harvard Children's in Boston is actually discussing with you about pricing scheme based on pulmonary function in patients taking ORKAMBI. I was wondering if that's a single isolated case, or have you seen that among the other payers or not? And then secondly, on the R&D front, I noticed in the press release you are adding one arm in the Phase III trial for 661 for patients who have one allele 508 and the other allele with residual CFTR function. You're adding one one-off therapy, KALYDECO arm. Is that due to a request from FDA and also, are you going to add monotherapy in the other Phase III trials or not, in 661 trial? Thanks.

第一個問題，可能問 Stuart：有報導指出，波士頓的哈佛兒童醫院其實正在與你們討論，針對服用 ORKAMBI 的病人，依肺功能制定的定價方案。我想知道這是單一的個案，還是你們也在其他付款方那邊看到類似情況？第二個問題，在研發方面，我注意到你們在新聞稿中提到，針對 661 的第三期試驗，你們新增了一個組別，納入一個等位基因為 508、另一個等位基因具有殘存 CFTR 功能的病人。你們新增了一個一次性的治療組別，也就是 KALYDECO 組。這是因為 FDA 的要求嗎？另外，你們是否也會在其他 661 的第三期試驗中加入單一療法組別，還是不會？謝謝。

Yes, Ying, so I'm not really going to comment on what discussions we are having with individual payers and plans. I'll say what we've said all along. Our belief is that all eligible patients deserve to have access to ORKAMBI, and for it to be a decision for the physician and patient, whether they want to initiate those patients on ORKAMBI. And on the 661 program, I'll hand that off to Jeff.

是的，Ying，所以我不會評論我們與個別付款方與保險計畫正在進行哪些討論。我只會重申我們一直以來所說的。我們相信所有符合資格的病人都應該能取得 ORKAMBI，而是否要讓這些病人開始使用 ORKAMBI，應由醫師與病人共同決定。至於 661 計畫，我把問題交給 Jeff。

Just to be clear, the design of the 661 program has not changed. We haven't added any new arms. The residual function arm always had in it both a placebo and an ivacaftor monotherapy, compared with 661 plus ivacaftor. So nothing has changed there.

為了釐清，661 計畫的設計沒有改變。我們沒有新增任何新的組別。殘存功能那個組別一直都同時包含安慰劑與 ivacaftor 單一療法，並與 661 加 ivacaftor 做比較。所以那部分沒有任何改變。

Okay. Thanks.

好的。謝謝。

Matthew Harrison, Morgan Stanley.

Matthew Harrison，摩根士丹利。

Great. Thanks for taking the question. So I just wanted to go back to the ENaC just for a second. I think you talked a little bit about the rationale, but maybe you could expand upon the rationale for combining with ORKAMBI, and then secondly, what specifically might you hope to see? Should we be looking for increased lung function? Should we be looking for a lowering of the exacerbation rate? What would you be hoping to see with that combination? Separately, on KALYDECO, I just want to make sure I understood your comments correctly. Are you saying that all of the growth came from increased penetration across the new gating mutations? Thanks.

很好。謝謝讓我提問。我想先回到 ENaC 的話題一下。我想你們談到了一些原理，但也許可以再延伸說明一下，為什麼要與 ORKAMBI 合併使用的理由；第二，你們具體希望看到什麼結果？我們應該期待肺功能提升嗎？還是應該期待急性惡化率下降？你們希望這個組合能帶來什麼？另外，關於 KALYDECO，我想確認我是否正確理解你們的評論。你們是說所有的成長都來自於在新的 gating 突變上的滲透率提升嗎？謝謝。

Maybe I'll take the R&D question first, the ENaC inhibitors. Ian describes this in terms of the ocean and seaweed, but I can't be nearly that eloquent, so I'll take it from a more scientific standpoint maybe. The way we think about ENaC, and the way ENaC inhibitors work, as you know, is that ENaC is a separate channel, it's a sodium channel, that is also involved in hydrating the secretions and the mucus in the lungs. And so you could think about it as -- and there's actually even an interaction with CFTR. CFTR is a chloride channel that helps hydrate the mucus, ENaC is a sodium channel. It helps hydrate the mucus. So the rationale, and it's based upon pre-clinical studies, is that if you combine ENaC inhibitor with a potentiator for example or a corrector potentiator, you'll get even better hydration of the mucus, which should then lead to better lung function.

也許我先回答研發問題，關於 ENaC 抑制劑。Ian 用海洋和海藻來形容，但我沒辦法講得那麼優雅，所以我可能從更科學的角度來說。我們對 ENaC 的看法，以及 ENaC 抑制劑的作用機制，如你所知，ENaC 是另一個通道，是鈉離子通道，也參與肺部分泌物與黏液的水合。所以你可以把它想成——而且它其實甚至與 CFTR 有交互作用。CFTR 是氯離子通道，幫助黏液水合；ENaC 是鈉離子通道。它也有助於黏液水合。因此其理論依據——並且是基於臨床前研究——是如果把 ENaC 抑制劑與例如增效劑（potentiator）或校正劑加增效劑（corrector potentiator）合併，你會得到更好的黏液水合，進而應該帶來更好的肺功能。

So what we're doing with the ENaC inhibitor program is we're asking the question, does the ENaC inhibitor alone have activity to help hydrate the mucus and improve lung function in all mutations? And then, if we take the ENaC inhibitor and add it to KALYDECO or ORKAMBI, can we get better hydration than we get with a single agent alone? The rationale is really based upon the work we've done in our human bronchial epithelial cell assays, that say when you add an ENaC inhibitor to a CFTR corrector or to a corrector plus potentiator, you actually get even better hydration. So the question is does that translate into the clinic in improvements in FEV1 and we definitely are going to be looking at hard end points like FEV1.

所以我們在 ENaC 抑制劑計畫中要問的問題是：ENaC 抑制劑單獨使用，是否在所有突變類型中都有活性，能幫助黏液水合並改善肺功能？接著，如果我們把 ENaC 抑制劑加到 KALYDECO 或 ORKAMBI 上，是否能比單一藥物更好地水合？這個理論依據主要來自我們在人類支氣管上皮細胞（human bronchial epithelial cell）測試中的工作，結果顯示當你把 ENaC 抑制劑加到 CFTR 校正劑，或校正劑加增效劑上時，確實能得到更好的水合。所以問題是：這是否能在臨床上轉化為 FEV1 的改善；我們肯定會觀察像 FEV1 這類硬終點。

And then in terms of the KALYDECO growth, it really is a combination of both label expansion and geographic expansion. For instance, in the US, we've had label expansions where the R117H patient population was added to the label at the back end of 2014, and then in March, we were also approved for use in children between two and five with eligible mutation. So there's label expansion here in the United States, and then outside of the US, it really has been geographic expansion, such as the G551D patients in Australia, where the uptake has been very rapid, and then also additional gating patients in a number of countries in the EU. So there really isn't one answer to what's been driving the KALYDECO revenue growth. It really has been that combination of label expansions into new populations, and geographic expansion into new markets.

至於 KALYDECO 的成長，確實是適應症標籤擴大與地理版圖擴張兩者的組合。例如在美國，我們有標籤擴大：在 2014 年底把 R117H 病人族群納入標籤；然後在 3 月，我們也獲准用於 2 到 5 歲、具有符合資格突變的兒童。所以在美國有標籤擴大；而在美國以外，主要是地理擴張，例如澳洲的 G551D 病人，採用速度非常快；此外在歐盟多個國家也涵蓋了更多 gating 病人。因此，推動 KALYDECO 營收成長的因素並非只有單一答案。確實是擴大標籤到新族群，以及拓展到新市場的組合。

All right.

好。

Mark Schoenebaum, Evercore ISI.

Mark Schoenebaum，Evercore ISI。

This is Odysseas, sitting in for Mark. Just a congratulations and thanks for taking my questions, but just a few questions. One, around the het-min trial, wondering about potential disclosure or lack of disclosure at the interim. If it doesn't hit and an expansion is required for an additional 150 patients.

我是 Odysseas，代替 Mark 出席。先恭喜一下，也謝謝讓我提問，不過我有幾個問題。第一個，關於 het-min 試驗，想請問在期中分析時是否可能揭露資訊，或是不揭露。如果沒有達標，且需要擴增額外 150 名病人。

The second question had to do with this lung clearance index. I'm just wondering whether Vertex has previously used that end point, any of the trials that have any data from any of these drugs, and if so, or if not, in terms of thinking about the -- how Vertex thought about the powering and design of the study, based on that? And then the last question, in terms of the next generation corrector and one coming by year-end, but as I understand, there will be additional probably next generation correctors -- potentiators, but next generation correctors that may follow. Just wondering if Vertex is perhaps eying, or if Vertex could quantify how many of those they may be eying to bring to the clinic in 2016? Thank you.

第二個問題是關於這個肺清除指數（lung clearance index）。我只是想了解 Vertex 之前是否曾在任何試驗中使用過這個終點、是否有任何這些藥物的試驗資料涵蓋該指標；若有或若沒有，Vertex 在思考研究的統計檢定力（powering）與設計時，是如何以此為基礎來考量的？最後一個問題是，關於下一代校正劑（corrector）以及年底前會有一個進展；但據我理解，後續可能還會有額外的、可能是下一代的校正劑——增效劑（potentiator）之外，但主要是後續可能跟進的下一代校正劑。想請問 Vertex 是否正在評估，或 Vertex 是否能量化在 2016 年可能打算推進多少個進入臨床？謝謝。

Sure. Let me -- this is Jeff. Let me take the last two questions and I'll turn it over to Ian on the disclosure question. Starting with the next-gen program, we've said previously that we have multiple next-gen correctors in lead optimization, which as you know, is the study of the drug life properties, anti-tox data from those molecules. As I said, we're on track to bring the first of those into the clinic this year, and our goal is to bring at least two or three additional behind that, following completion of lead optimization for those additional molecules, and to compare several different next-generation correctors.

好的。我——我是 Jeff。我先回答最後兩個問題，然後把揭露（disclosure）問題交給 Ian。先從下一代計畫開始，我們先前已說過，我們有多個下一代校正劑正處於先導優化（lead optimization）階段；如你所知，這包括對分子的藥物樣特性研究，以及這些分子的抗毒性（anti-tox）資料。如我所說，我們按計畫在今年把其中第一個帶入臨床；我們的目標是在其後，於完成其他分子的先導優化後，再帶至少兩到三個進入臨床，並比較數個不同的下一代校正劑。

Then your question about lung clearance index. Lung clearance index is actually a fairly widely-used measure of the ability to empty the lungs of air effectively, and there is data from a number of studies showing, for instance, that when G551D patients are treated with KALYDECO, there is a significant improvement in lung clearance index, and we're happy to send you some of those studies. It is an end point that has been pharmacologically validated, if you want to think about it that way.

接著是你關於肺清除指數的問題。肺清除指數其實是一個相當廣泛使用的衡量指標，用來評估肺部有效排出空氣的能力；而且有多項研究的資料顯示，例如當 G551D 病患接受 KALYDECO 治療時，肺清除指數會有顯著改善；我們也很樂意把其中一些研究提供給你。如果你想用那種方式來理解，它是一個已在藥理學上被驗證（pharmacologically validated）的終點。

Odysseas, thanks for the question. Just to refer to an earlier comment Jeff Leiden made, which was the initial part, the initial cohort of patients that enters the het-mins study with 661, and the idea of that is there is a futility assessment. That futility assessment, if an independent advisory board deems that it is worth progressing forward, we will just continue to recruit patients, and the study will be ongoing. We will not be at a disclosure point at that point. We'll just continue to recruit into the study and wait for the complete and final results of that study.

Odysseas，謝謝你的問題。我想回到 Jeff Leiden 先前的一個評論，也就是最初的部分：進入 het-mins 研究、使用 661 的第一批（initial cohort）病患，其設計理念是要進行無效性（futility）評估。如果獨立諮詢委員會認為值得繼續推進，我們就會持續招募病患，研究也會持續進行。在那個時間點我們不會進行資訊揭露。我們只會繼續招募並等待該研究完整且最終的結果。

If the Board deems that it is futile, effectively futile in dosing those patients, they will advise us so, and we will curtail the study. On stopping that study and working the patients off drug, we will provide a disclosure to let you know that study is no longer going forward. So I think the way to think about this is if there is no news, it is because the study will progress, and they will continue to recruit het-min patients and if there is an early closure of that study, we'll advise you at that point in time.

如果委員會認為對這些病患給藥在效果上是無效、等同於徒勞（futile），他們會向我們提出建議，我們就會縮減並終止該研究。在停止該研究並讓病患停藥（working the patients off drug）時，我們會進行揭露，讓你知道該研究不再繼續推進。所以我認為可以這樣理解：如果沒有消息，表示研究仍在推進、也會持續招募 het-min 病患；如果該研究提早結束，我們會在那個時間點通知你。

Just to clarify, so there won't be necessarily an increase in the number of patients on clinicaltrials.gov or anything of that sort?

我確認一下，所以 clinicaltrials.gov 上的病患人數之類的，不一定會增加或有任何那類變動？

No, there won't be any disclosures.

不會，不會有任何揭露。

Thank you very much.

非常感謝。

Robyn Karnauskas, Deutsche Bank.

Robyn Karnauskas，德意志銀行（Deutsche Bank）。

Two questions, one for Stuart, one for Ian. Stuart, you have talked a lot about in CF centers there could be a backlog of processing within the CF centers, and there may not be a lot you can do about that. Can you just talk a little bit about what you're seeing, or anything you've done to help that process, as patients move through? And if it's better or in line with your expectations? And then for Ian, a lot of your competitors or comps are diversifying, and you still are really a CF company. What are your thoughts on the importance of diversification over the next few years? Thanks.

兩個問題，一個問 Stuart，一個問 Ian。Stuart，你談到很多關於在 CF 中心可能會有處理上的積壓（backlog），而你們可能也無能為力。你能否多談一些你們看到的情況，或你們做了哪些事來協助病患在流程中往前推進？以及目前是否更好、或符合你們的預期？另外問 Ian，你們很多競爭對手或同業都在多元化，但你們仍然很像是一家以 CF 為主的公司。你對未來幾年多元化的重要性有什麼看法？謝謝。

Robyn, hi, it's Stuart here. Whilst it's early days, I think our experience in the first four weeks is the factors we were anticipating are really playing out, as we anticipated they would. Those factors, just to remind you, is the volume of patients is, obviously, much greater than it was when KALYDECO was initially approved, just the G551D patients. So there's a volume of patients that centers need to get in. Then obviously, when a physician is making the decision to start a patient on a new drug, then obviously, there is a fair amount of discussion, education is going to want to go on there, explaining the product, the mechanism of action, how to take it, all those sorts of things. And then, obviously, we move on to the reimbursement approval process.

Robyn，你好，我是 Stuart。雖然現在還算早期，但我認為我們在前四週的經驗顯示，我們原先預期的因素確實正在發生，正如我們所預期。提醒一下，這些因素包括：病患量顯然比 KALYDECO 最初獲批時（僅 G551D 病患）大得多。因此中心需要安排進來的病患量就很大。另外，當醫師決定讓病患開始使用一種新藥時，通常會有相當多的討論與衛教，包括解釋產品、作用機轉、如何服用，以及諸如此類的事項。接著，當然就進入給付／報銷（reimbursement）核准流程。

And so all of those factors that we anticipated prior to launch being involved in how the launch is going to go, have certainly been playing out exactly as we thought they would. In terms of what we're doing to support centers, we're doing a number of things, clearly providing education materials to support their discussions with their patients. We are providing them with help in terms of the sort of materials they need to submit to the various payers, be it prior authorization documentation, and stuff like that, providing them help with what documentation they are going to need, where the right place to send it is. And then from a patient support point of view, obviously our patient services group is there to support individual patients navigate the reimbursement process, as well. And so we are, as compliantly as possible, we are providing as much support as we can, to help patients get access to the medicine. Second point, I'll pass it over to Ian.

因此，我們在上市前預期會影響上市進展的所有因素，確實都完全如我們所想地在發生。至於我們如何支援中心，我們做了很多事情：很明確地，我們提供衛教材料來支援他們與病患的討論。我們也在協助他們準備提交給各個付款方（payers）的材料，例如事前授權（prior authorization）文件等，協助他們了解需要哪些文件、以及應該送到哪裡。此外，從病患支持的角度來看，我們的病患服務團隊也會協助個別病患一同完成給付流程的導航。因此，在盡可能符合合規（compliantly）的前提下，我們提供我們能提供的最大支持，協助病患取得藥物。第二點我交給 Ian。

Robyn, thanks for that question regarding, we're focused on CF. We're very pleased about that. But also, I would say that we still need to continue to be focused on CF, and part of our let's say, corporate or business development strategy, as well as our investment into research at Vertex is about strengthening our position and creating even better combination medicines to treat more patients in CF. So that is one tactic, and so we continue in CF and I think it is -- it behooves the Company to continue to raise the bar in terms of the benefit we provide patients with our medicines, and that's why we reinvest.

Robyn，謝謝你關於我們聚焦於 CF 的問題。我們對此非常滿意。但我也想說，我們仍需要持續聚焦於 CF；而我們在 Vertex 的企業／商務開發策略，以及對研發的投資，其中一部分就是要強化我們的地位，並打造更好的聯合用藥（combination medicines）來治療更多 CF 病患。這是一個策略方向；因此我們持續深耕 CF。我認為公司確實應該持續提高門檻（raise the bar），在我們藥物能為病患帶來的效益上不斷提升，這也是我們再投資的原因。

We also reinvested in other areas within the Company, and I hope that later this year and early next year we can tell you a little bit more about those other disease areas that we're in, as well as our other business development efforts, which are looking to expand our scientific footprint, and then also just to consider other products that may diversify and stage our pipeline. It tends to be earlier stage ideas. I think that's appropriate for a Company at our stage, as we progress forward, and our priority is still cystic fibrosis. I'll throw it over to Jeff Leiden, though, because I think there's just much more of a strategic comment that's worth making here, which is, while we're successful in CF, we're not taking our eye off that we want to go into other disease areas. And maybe Jeff, you have a comment?

我們也在公司內其他領域進行再投資；我希望在今年稍晚以及明年初，我們能向你多分享一些我們所涉足的其他疾病領域，以及我們其他的商務開發工作；這些工作旨在擴大我們的科學版圖，同時也考量其他可能讓我們的產品線更多元、並分階段推進我們研發管線（pipeline）的產品。這些通常是較早期的想法。我認為以我們公司目前的階段來說，這樣是合適的；隨著我們往前推進，我們的優先順序仍然是囊性纖維化。不過我想把問題交給 Jeff Leiden，因為我覺得這裡還有一個更值得提出的策略性評論：也就是，雖然我們在 CF 上很成功，但我們並沒有忽視我們也想進入其他疾病領域。Jeff，也許你可以補充一下？

I think Ian said it well. If I were to say it in a simple way, I think of this as three strategic objectives. Number one, no doubt about it, is CF. Not only increasing the number of patients that we can treat with new medicines, but actually increasing the benefit for all the patients that we are treating. We said many times our goal is to get to the majority, more than 90% of patients with medicines that have KALYDECO-like or better effects. I think we're executing well on that, and we're well on track.

我認為 Ian 說得很好。如果要我用簡單的方式來說，我把這看作三個策略目標。第一，毫無疑問，是囊性纖維化（CF）。不僅是增加我們能用新藥治療的病患人數，更是實際提升我們正在治療的所有病患所獲得的效益。我們多次說過，我們的目標是讓大多數、超過 90% 的病患，能使用具有類似 KALYDECO 或更佳效果的藥物。我認為我們在這方面執行得很好，而且進度也很符合預期。

At the same time, obviously, we are investing in areas outside of CF. As I've said, we'll bring more new compounds into the clinic this year Vertex than we ever have in the history of the Company. We're not talking a lot about that yet, but you'll start to hear more news as we begin to get clinical results I think later this year, and certainly for next year. And then the third part, as Ian said, is that we're going to have the financial resources to also invest in innovation outside the Company, and we're spending significantly more time, effort and money on our BD activities. You've heard about a couple of deals, but I think you can anticipate more, again, typically focused on earlier-stage scientific platforms or assets. It's really a three-legged stool. I think with the launch of ORKAMBI, we'll now have the financial wherewithal to invest in all three parts of the stool.

同時，很明顯地，我們也在投資 CF 以外的領域。如我所說，今年 Vertex 將把比公司歷史上任何一年都更多的新化合物帶入臨床。我們目前還不會談太多，但當我們開始取得臨床結果時，你們會聽到更多消息，我想是在今年稍晚，當然也會延續到明年。第三部分，如 Ian 所說，我們也將擁有財務資源，去投資公司外部的創新，我們在商務開發（BD）活動上投入了顯著更多的時間、精力與資金。你們已經聽到幾筆交易，但我想你們可以預期還會有更多，而且通常會聚焦在較早期的科學平台或資產。這真的是一個三腳凳。我認為隨著 ORKAMBI 的上市，我們現在將具備財務實力，去投資這三個面向。

Phil Nadeau, Cowen and Company.

Phil Nadeau，Cowen and Company。

Just two, one scientific, actually, both on clinical development. First on VX-661 Phase III, have you ever disclosed what the futility analysis hurdle is, or if not, would you care to disclose it now? Second, on the new, the second-generation correctors, can you give us some idea of what the clinical development path is likely for those? Specifically, how quickly could they get into combination therapy regimens with an FEV1 end point? Thank you.

兩個問題，一個是科學面的，其實兩個都與臨床開發有關。第一個關於 VX-661 第三期試驗，你們是否曾披露過無效性分析（futility analysis）的門檻？如果沒有，現在願意披露嗎？第二個關於新的第二代校正劑（correctors），你們能否給我們一些概念，這些藥物可能的臨床開發路徑會是什麼？具體來說，它們最快能多快進入以 FEV1 為終點的聯合治療方案？謝謝。

Thanks for both. We haven't disclosed the hurdle, and we won't be disclosing it today. As Ian said, I think the first news that you would get on that is if we didn't meet the hurdle and the study was stopped, we would disclose at that point what was going on. With respect to the second-generation correctors, we really see them following a fairly straightforward development path. We've pioneered the way here with our previous medicines that go into Phase I in normal, single ascending dose, multi ascending dose, and following, hopefully successful safety results from those studies, we would put them both as monotherapy and as combination therapy into patients. I think we've figured out, we've learned a lot over the last few years about how to do those studies very quickly, very efficiently, with small numbers of patients. I think we can get pretty definitive data using FEV1, as well as other end points, on how they fare both by themselves and in combination.

兩個問題都謝謝。我們沒有披露那個門檻，今天也不會披露。如 Ian 所說，我想你們會得到的第一個消息是：如果我們沒有達到門檻而研究被停止，我們會在那個時點披露當時的情況。至於第二代校正劑，我們確實認為它們會遵循相當直接的開發路徑。我們在這方面已經開創了做法：先在健康受試者進行第一期試驗，包括單次遞增劑量（SAD）、多次遞增劑量（MAD）；在這些研究取得（希望是）成功的安全性結果後，我們會把它們以單藥治療以及聯合治療的方式放到病患中進行。我想過去幾年我們學到很多，知道如何用少量病患非常快速、非常有效率地完成這些研究。我認為我們可以用 FEV1 以及其他終點，取得相當明確的數據，來看它們單獨使用以及聯合使用時的表現。

Great. Thank you.

很好。謝謝。

Tony Butler, Guggenheim Partners.

Tony Butler，Guggenheim Partners。

Thanks very much. Jeff, two brief questions. One is, eliminating the sodium channel compounds for the moment, is there a rationale for a next-gen corrector to actually be QD or BID, such that it's more easily formulated with either ivacaftor and/or 661? And the second question is, is there any rationale from HB experiments that actually suggest to you that there may be the need for three correctors in addition to a potentiator? Thanks.

非常感謝。Jeff，兩個簡短問題。第一個是，先暫時不談鈉通道化合物，下一代校正劑是否有理由設計成每日一次（QD）或每日兩次（BID），以便更容易與 ivacaftor 和／或 661 共同製劑？第二個問題是，從 HB 實驗來看，是否有任何理由讓你們認為，除了增效劑（potentiator）之外，可能還需要三種校正劑？謝謝。

Thanks for both questions. So with respect to the formulation question, our goal always has been to make it as easy as possible for these patients to take their medicine, because they do take very large numbers of pills every day, and so we continue to push for co-formulated products. That's certainly our goal, into one pill or a small number of pills, and either QD or BID, both of those seem pretty acceptable to patients. That's certainly our target product profile with the next-gen correctors and combinations. Your other question was, could we need three correctors? The answer is we don't yet fully know, but certainly our goal is to try to keep this to as few medicines as possible, simply from drug-drug interaction standpoint, from a co-formulation standpoint. So again, if you ask me what our target product profile was today, it would be a first-gen corrector, a second-gen corrector and potentiator.

兩個問題都謝謝。關於製劑的問題，我們的目標一直是讓病患盡可能容易服藥，因為他們每天確實要吃非常多的藥丸，所以我們會持續推動共同製劑產品。這當然是我們的目標：做成一顆或少數幾顆藥丸，並且是每日一次或每日兩次，這兩種頻次對病患而言似乎都相當可接受。這確實是我們對下一代校正劑與其組合的目標產品特性（target product profile）。你另一個問題是：我們是否可能需要三種校正劑？答案是我們目前還不完全知道，但我們的目標當然是盡量把藥物數量維持在最少，主要是從藥物交互作用以及共同製劑的角度來看。所以，如果你今天問我我們的目標產品特性是什麼，那會是第一代校正劑、第二代校正劑，再加上一個增效劑。

Thank you. That's helpful.

謝謝。這很有幫助。

Operator, we have time for two more questions.

接線員，我們還有時間再問兩個問題。

Brian Skorney, Baird.

Brian Skorney，Baird。

I guess I just wanted to get your temperature on how we should be thinking about pricing of the VX-661 combination, in the context of ORKAMBI and KALYDECO's price. They are obviously at different price points, but they are in different patient populations right now. But based on the 661 combo studies, there's probably going to wind up being significant overlap between KALYDECO and ORKAMBI patients. I guess about 80% of KALYDECO responders would probably show improvement on VX-661 plus ivacaftor, based on the Phase II data, and it doesn't look like there would be a meaningful amount of clinical efficacy above and beyond ORKAMBI for the combo. So I guess, is it more important to you to maintain price per patient for KALYDECO responders, or to try to get ORKAMBI patients switched to the VX-661 combo? Because it doesn't seem like you could really do both.

我想我只是想了解一下，你們希望我們如何看待 VX-661 聯合療法的定價，尤其是在 ORKAMBI 與 KALYDECO 的價格背景之下。它們顯然在不同的價格點，但目前對應的是不同的病患族群。不過根據 661 聯合療法的研究，KALYDECO 與 ORKAMBI 的病患之間，最後可能會出現顯著重疊。我想大約 80% 的 KALYDECO 反應者，根據第二期數據，可能在 VX-661 加 ivacaftor 上也會有改善，而且看起來這個組合在臨床療效上不太可能明顯超越 ORKAMBI。所以我想問的是：對你們而言，更重要的是維持 KALYDECO 反應者的每位病患價格，還是嘗試讓 ORKAMBI 病患轉換到 VX-661 的組合？因為看起來你們不太可能兩者兼得。

Brian, I think the most important things to us overall are to increase the number of patients that we're able to bring a benefit to, and continue to increase the benefit we deliver for the patients that we are able to treat. That's our overall strategy, and KALYDECO combined with VX-661 is a part of that overall strategy. But to really be commenting on price right now is way too early. As you know, we've got this broad Phase III program, studying it across multiple patient populations, and until we see the results, both safety and efficacy across those different patient populations, it would be inappropriate to be speculating on how we might price that combination.

Brian，我認為對我們整體而言最重要的是，增加我們能夠帶來效益的病患人數，並持續提升我們能治療之病患所獲得的效益。這是我們的整體策略，而 KALYDECO 與 VX-661 的組合是這個整體策略的一部分。但現在就評論價格還太早了。如你所知，我們有一個廣泛的第三期計畫，會在多個病患族群中進行研究；在我們看到結果之前——包括在不同病患族群中的安全性與療效——去推測我們可能如何為該組合定價是不恰當的。

Then I guess would you perceive any benefit outside of a double corrector potentiator combination to have patients on a 661 ivacaftor combo as opposed to ORKAMBI, if the Phase II data winds up holding up and they look pretty similar efficacy-wise?

那我想請問，如果第二期數據最終能夠成立、而且在療效上看起來相當接近，您是否認為，相較於 ORKAMBI，讓病人使用 661 與 ivacaftor 的組合（而非雙校正劑加增效劑的組合）在雙校正劑／增效劑組合之外還有任何額外的好處？

I'm not sure I understand your question. Can you ask that again? A double corrector combination--

我不確定我理解您的問題。您可以再問一次嗎？雙校正劑組合——

So basically what I'm getting at is, would there be a reason to try to get patients on ORKAMBI switched to 661, in your view, if the efficacy profiles are relatively similar?

所以我基本上想問的是，如果療效特徵相對類似，依您看，是否有理由嘗試讓使用 ORKAMBI 的病人改換成 661？

I think it really depends on the totality of the profile, and whilst efficacy is one part of the equation, obviously, there's safety, as well. So it's really going to depend on what the physician and patients think of the overall profile of the medicine, if it's successful in that population, compared to their experience with ORKAMBI. So at this stage, it's really a very hypothetical discussion, Brian. We'll wait and see how the Phase III program plays out, and when we've got the results in hand, we'll be able to have a much more informed discussion about which patient populations may be eligible for VX-661 and ivacaftor.

我認為這真的取決於整體的特徵；雖然療效是方程式的一部分，但顯然安全性也是。因此，若該藥物在那個族群中成功，最終將取決於醫師與病人如何看待這個藥物的整體特徵，並與他們使用 ORKAMBI 的經驗相比。所以在這個階段，Brian，這其實是一個非常假設性的討論。我們會等待第三期計畫的進展；等我們拿到結果後，就能就哪些病人族群可能適用 VX-661 與 ivacaftor 進行更有依據的討論。

Okay. Fair enough. Thanks.

好的。有道理。謝謝。

Liisa Bayko, JMP Securities.

JMP Securities 的 Liisa Bayko。

I guess you saved the best for last. Thank you very much.

我想你們把最精彩的留到最後了。非常感謝。

Absolutely.

當然。

First question, I just wanted to better understand the guidance. So if we extrapolate the results this quarter and just assume it's flat for the remainder of the year, we actually get to a number that's slightly above your guidance. So I'm just wondering if there was any stocking or if there's some FX considerations, or greater gross to net in the future. What -- help us better understand the guidance you provided for KALYDECO?

第一個問題，我只是想更清楚地理解你們的指引。如果我們外推本季的結果，並假設今年剩餘期間都持平，算出來的數字其實會略高於你們的指引。所以我想知道是否有任何備貨因素、或匯率（FX）考量、或未來毛額到淨額（gross-to-net）折讓會更大。請——幫我們更好地理解你們對 KALYDECO 所提供的指引？

Liisa, thanks. You certainly did save the best for last. Congratulations. Your math is correct. If you take the first six months of this year and then take this quarter and multiply it by 2, which is a way of just saying the last three quarters are the same as the second, and the first quarter's already done, you do get to slightly above the $590 million. That's correct. I made comments earlier on the call, though, which is we do anticipate patients that we expected to come onto KALYDECO treatment will now go towards the 661 Phase III studies. And clearly, we're trying to estimate that, but we have taken a conservative approach, and we anticipate that will affect the growth of KALYDECO, specifically in Europe, and therefore, we're not anticipating significant growth in the second half of this year with KALYDECO.

Liisa，謝謝。你確實把最精彩的留到最後了。恭喜。你的數學沒錯。如果你把今年前六個月的數字，再把本季乘以 2——也就是假設最後三個季度與第二季相同，而第一季已經結束——確實會略高於 5.90 億美元。沒錯。不過我在先前的電話會議中也提到，我們確實預期原本會開始接受 KALYDECO 治療的病人，現在會轉而參與 661 的第三期研究。而且我們當然在嘗試估算其影響，但我們採取了保守作法，並預期這會影響 KALYDECO 的成長，特別是在歐洲；因此，我們不預期今年下半年 KALYDECO 會有顯著成長。

Okay. That makes sense. Thank you. I didn't totally put that together. Thanks. And then just a final question. Again, I know a lot of people have asked, but on this lung clearance index, can you maybe give us what assumptions you made in this population, or how you powered it? And what clinical difference you expect to see or make sense, just because we're not as familiar with it, and we haven't seen as much of the data. That would be very helpful. Thank you.

好的。這就說得通了。謝謝。我之前沒有完全把這點連起來。謝謝。然後最後一個問題。我知道很多人都問過，但關於這個肺清除指數（lung clearance index），你們能否談談在這個族群中做了哪些假設、或是如何進行樣本數／檢定力（power）設計？以及你們預期會看到、或認為合理的臨床差異是什麼？因為我們對它不太熟悉，也沒有看過那麼多數據。如果能說明會非常有幫助。謝謝。

Thanks for the question. This is Jeff. We haven't disclosed the numbers there, and probably won't until we get towards the end of the study. There is a fair amount of literature out there that we can send you on what kind of numbers one might see, as I said, with KALYDECO as an example. The study is 200 patients, so it's appropriately powered to see the kinds of differences that we think would be important to see clinically and statistically.

謝謝你的問題。我是 Jeff。我們尚未披露那方面的數字，而且可能要到研究接近尾聲才會披露。目前有相當多的文獻可供參考，我們可以寄給你，說明可能會看到什麼樣的數值；如我所說，可以以 KALYDECO 作為例子。這項研究有 200 位病人，因此在檢定力設計上是足夠的，能夠看出我們認為在臨床與統計上都重要的差異。

Okay. Thanks a lot.

好的。非常感謝。

Okay. That's going to conclude the call. We appreciate everybody joining us tonight. The IR team is available in the office tonight if anyone has additional follow-up questions. I'll also mention that we will be presenting at a few investor conferences in the coming months, and in early October, we will plan to host analysts and investors at the North American CF conference in Phoenix. Stay tuned for details on that. Thanks, and have a good night.

好的。電話會議到此結束。感謝各位今晚加入。如果有人有其他後續問題，投資人關係（IR）團隊今晚會在辦公室待命。我也要提到，接下來幾個月我們會在幾場投資人會議上發表；並且在 10 月初，我們計畫在鳳凰城（Phoenix）的北美 CF 會議上接待分析師與投資人。相關細節請持續關注。謝謝，祝各位晚安。

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

各位女士先生，感謝參與今天的電話會議。本次議程到此結束，您可以掛線。祝各位有美好的一天。