福泰製藥 (VRTX) 2013 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceuticals first quarter 2013 financial results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time.

各位女士、各位先生，大家好，歡迎參加 Vertex Pharmaceuticals 2013 年第一季財務業績電話會議。此時，所有與會者將以僅收聽模式參與。稍後我們將進行問答環節，屆時將提供相關指示。

(Operator Instructions.)

（接線員指示。）

As a reminder, this conference call is being recorded.

提醒各位，本次電話會議將被錄音。

I would now like to turn the conference over to your host, Mr. Michael Partridge, Head of Investor Relations. You may begin.

現在我想把電話會議交給本次主持人——投資人關係主管 Michael Partridge 先生。您可以開始了。

Thank you, operator and good evening to everyone.

謝謝接線員，也祝各位晚安。

Joining me on tonight's call are Dr. Jeff Leiden, Vertex's Chairman and CEO, Stuart Arbuckle, Chief Commercial Officer and Ian Smith, Chief Financial Officer. Jeff will begin with a review of our progress this year in executing against our long-term strategy of creating innovative medicine with a focus on specialty diseases, then Stuart will comment on market trends for our key medicines, Kalydeco for people with cystic fibrosis, who have the G551D mutation and Incivek for hepatitis C. And in to close, Ian will review the first quarter financial results and update our 2013 net guidance for Kalydeco net revenues.

今晚與我一同參與電話會議的有：Vertex 董事長兼執行長 Jeff Leiden 博士、商務長 Stuart Arbuckle，以及財務長 Ian Smith。Jeff 將先回顧我們今年在執行長期策略方面的進展——聚焦於專科疾病、創造創新藥物；接著 Stuart 將就我們兩項關鍵藥物的市場趨勢發表看法：用於帶有 G551D 突變之囊性纖維化患者的 Kalydeco，以及用於 C 型肝炎的 Incivek。最後 Ian 將回顧第一季財務結果，並更新我們對 2013 年 Kalydeco 淨營收的指引。

After prepared remarks, Robert Kauffman, Chief Medical Officer and Peter Mueller, Chief Scientific Officer will join us for a question-and-answer period. After the call, we will be available in our offices for follow-up.

在預先準備的發言之後，醫務長 Robert Kauffman 與科學長 Peter Mueller 也將加入問答環節。會後，我們將在辦公室提供後續追蹤的聯繫。

Before we begin, I will note that information discussed on this conversation call includes forward-looking statements which are subject to the risks and uncertainties discussed in detail in our 10-K reports which has been filed with the Securities and Exchange Commission and also in the press release announcing our financial results tonight. These statements, including without limitation, those regarding the commercial performance of Incivek and Kalydeco, our development and expectations and our guidance are based on management's current assumptions and are subject to the risks and uncertainties that could cause actual outcomes and events to differ materially.

在開始之前，我要說明：本次電話會議所討論的資訊包含前瞻性陳述，並受我們已向美國證券交易委員會（SEC）提交之 10-K 報告中所詳述的風險與不確定性影響，亦受今晚公布財務結果之新聞稿中所述風險影響。這些陳述（包括但不限於）關於 Incivek 與 Kalydeco 的商業表現、我們的研發進展與預期，以及我們的指引，係基於管理層目前的假設，並可能因風險與不確定性而使實際結果與事件與所述內容出現重大差異。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of these measures and a reconciliation of GAAP to non-GAAP is available in our first quarter 2013 financial press release which is on our website, and I would also refer you to the information on slide 4 of tonight's webcast.

本次電話會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用這些指標的資訊，以及 GAAP 與非 GAAP 之間的調節表，已載於我們網站上的 2013 年第一季財務新聞稿中；同時也請參考今晚網路直播投影片第 4 頁的資訊。

I will now turn it over to Jeff.

現在我把時間交給 Jeff。

Thanks, Michael.

謝謝你，Michael。

Good afternoon, everyone. I'm pleased to discuss with you the progress that Vertex has made in 2013.

各位下午好。我很高興與各位討論 Vertex 在 2013 年所取得的進展。

Earlier this year, we identified key priorities that would enable you to measure the progress of our Business. In January at the JPMorgan conference, I outlined three strategic imperatives for our Business that would position us for long-term growth. First, prioritizing our development investments to advance our late stage medicines. We have important late stage medicines in development for cystic fibrosis, hepatitis C, and autoimmune diseases, and our goal is to provide these therapies to patients, their families and health care providers as soon as possible.

今年稍早，我們確立了幾項關鍵優先事項，讓各位能衡量我們業務的進展。在 1 月的摩根大通（JPMorgan）會議上，我概述了三項能讓我們具備長期成長定位的策略要務。第一，優先配置研發投資，以推進我們後期階段的藥物。我們在囊性纖維化、C 型肝炎與自體免疫疾病領域都有重要的後期研發藥物，我們的目標是盡快將這些療法提供給病患、其家屬與醫療照護提供者。

Second, focus on continuing to create innovative medicines for serious diseases out of our R&D efforts. Making ground breaking new medicines is the reason Vertex was founded. It continues to define who we are today.

第二，持續聚焦於透過研發努力，為嚴重疾病創造創新藥物。研發突破性新藥正是 Vertex 創立的初衷。這也持續定義了我們今天的定位。

And third, maintaining our financial strength. We recognize that we're in an important period of investment to realize sustained growth opportunities in the near future, and the funding of this investment while maintaining our balance sheet strength is an important priority.

第三，維持我們的財務實力。我們認知到目前正處於一個重要的投資期，以在不久的將來實現可持續的成長機會；在維持資產負債表穩健的同時為這些投資提供資金，是一項重要優先事項。

So far, in 2013 we have accomplished a great deal to advance our late stage medicines and show the potential to bring further ground-breaking therapies to patients. We also continue to maintain our financial strength with a good financial performance for the first quarter. In cystic fibrosis, we received breakthrough designation from the US FDA for Ivacaftor as monotherapy. We have multiple studies underway that could potentially expand the Kalydeco label. We are on track to have the first clinical data for Ivacaftor monotherapy outside of G551D in the second half of 2013.

截至目前，2013 年我們已完成許多工作，以推進後期藥物並展現為病患帶來更多突破性療法的潛力。我們也在第一季以良好的財務表現持續維持財務實力。在囊性纖維化方面，我們的 Ivacaftor 單藥治療獲得美國 FDA 的突破性療法認定。我們正在進行多項研究，可能擴大 Kalydeco 的適應症標籤。我們按計畫將於 2013 年下半年取得 Ivacaftor 單藥治療在 G551D 以外族群的首批臨床數據。

We also received breakthrough designation for the combination of Ivacaftor with our lead corrector molecule, VX809. With the VX809 plus Ivacaftor combination, we reached agreement with the regulatory authorities and have now begun a phase III program that will evaluate six months of treatment in 1,000 patients homozygous for the Delta 508 mutation. We anticipate that we will receive phase III data and submit an MDA for this combination in 2014.

我們也針對 Ivacaftor 與我們領先的校正劑分子 VX809 的合併療法獲得突破性療法認定。就 VX809 加 Ivacaftor 的合併療法而言，我們已與監管機關達成一致，並已啟動第三期計畫，將在 1,000 名 Delta 508 突變純合子患者中評估為期六個月的治療。我們預期將於 2014 年取得第三期數據，並就此合併療法提交 MDA。

We also reported phase II data earlier this month with another corrector, VX661, that has further validated the strategy of combining a corrector and a potentiator to treat CF patients with two copies of the Delta 508 mutation. Also, we announced that we continue to advance an additional corrector, VX983, and we expect to start a combination study with this compound in people with two copies of the Delta 508 mutation in the second half of this year.

本月稍早，我們也公布了另一款校正劑 VX661 的第二期數據，進一步驗證了將校正劑與增效劑（potentiator）合併，用於治療帶有兩個 Delta 508 突變拷貝之囊性纖維化患者的策略。此外，我們宣布持續推進另一款校正劑 VX983，並預期於今年下半年在帶有兩個 Delta 508 突變拷貝的人群中啟動該化合物的合併研究。

In hepatitis C, we have initiated two 12-week studies with an interferon-free, all-oral regimen of our nucleotide VX135 in combination with ribavirin, and one of these studies is now fully enrolled. Our strategy is to conduct multiple phase II studies of VX135 in multiple combinations with other DAs in phase II to position us to initiate pivotal development of VX135 in 2014. This quarter we are starting our first phase II study in HCV patients combining VX135 with another DA, Bristol Myers Squibb's NS5A inhibitor, Daclatasvir.

在 C 型肝炎方面，我們已啟動兩項為期 12 週的研究，採用不含干擾素、全口服的療程：以我們的核苷酸類藥物 VX135 聯合利巴韋林（ribavirin），其中一項研究目前已完成收案。我們的策略是在第二期中，針對 VX135 與其他 DA 的多種合併方案進行多項第二期研究，以使我們能在 2014 年啟動 VX135 的關鍵性（pivotal）開發。本季我們將啟動首項在 HCV 患者中進行的第二期合併研究，將 VX135 與另一款 DA——百時美施貴寶（Bristol Myers Squibb）的 NS5A 抑制劑 Daclatasvir——聯合使用。

Financially, we are making significant investments which we believe are important to position us for sustained future growth. These investments are focused in R&D for the creation of meaningful new medicines. As part of the strategy we outlined in January, we described how we would control our operating expense and reduce our SG&A investment compared to prior years, and thereby direct our investments towards our pipeline and research efforts. These actions are reflected in our Q1 results which Ian will cover in more detail.

在財務方面，我們正進行重大投資，我們相信這些投資對於讓公司具備可持續的未來成長定位至關重要。這些投資主要聚焦於研發，以創造具重大意義的新藥。作為我們在 1 月所概述策略的一部分，我們說明了將如何控管營運費用，並相較於過往年度降低 SG&A 投入，從而把投資導向我們的產品線與研究工作。這些行動已反映在我們第一季的結果中，Ian 將進一步詳述。

To maintain financial strength, we are also seeking to maximize revenues of our approved medicines. Stuart will provide some color on this in a moment, but I will say that I am pleased with our performance this quarter, which shows our important position in hepatitis C and also demonstrates the value of Kalydeco for certain people with CF. In summary, our strategy has provided hope for people with serious diseases and has created significant value for shareholders and a platform for long-term growth.

為了維持財務實力，我們也致力於最大化已核准藥物的營收。Stuart 稍後會就此提供更多說明；但我想先表示，我對本季的表現感到滿意，這顯示我們在 C 型肝炎領域的重要地位，也展現 Kalydeco 對部分囊性纖維化患者的價值。總結而言，我們的策略為嚴重疾病患者帶來希望，為股東創造顯著價值，並建立長期成長的平台。

Now, I would like to turn it over to Stuart.

現在，我想把時間交給 Stuart。

Thank you, Jeff, and good afternoon.

謝謝你，Jeff，各位下午好。

I will provide some background and commentary on our improvements in Incivek for genotype 1 chronic hepatitis C infection and Kalydeco for CF patients who have the G551D mutation. Starting with in Incivek, we launched Incivek for hepatitis C in May 2011 and now, just two years later, we have treated more than 60,000 patients in the United States. While fewer patients are starting treatment for hepatitis C compared to this time a year ago, the hepatitis C market remains substantial and Incivek continues to be the market leader with approximately 75% of new patients in the US, a number that is unchanged since launch.

我將就 Incivek 在基因型 1 慢性 C 型肝炎感染，以及 Kalydeco 在帶有 G551D 突變之囊性纖維化（CF）患者的進展，提供一些背景與評論。先從 Incivek 開始：我們於 2011 年 5 月推出用於 C 型肝炎的 Incivek，而如今僅僅兩年後，我們已在美國治療超過 60,000 名患者。儘管與一年前相比，開始接受 C 型肝炎治療的患者人數較少，但 C 型肝炎市場仍然可觀，而 Incivek 仍是市場領導者，在美國新治療患者中約占 75%，此一比例自上市以來維持不變。

Vertex recorded $206 million for net revenues in Incivek in the first quarter. We expect Incivek to remain the market-leading therapy throughout 2013. However, the number of hepatitis C patients starting treatment in the US has been in decline since the second quarter of last year, and this trend is likely to continue in the US. Outside of the US, Janssen market's Telaprevir is Incivo, and Vertex receives a royalty. Incivo availability has continued to expand to additional countries and based on Janssen's sales in the first quarter of 2013, Vertex earned $39 million in royalties. Janssen has attributed the strong performance of Incivo in the first quarter to a continued successful rollout of Incivo in Latin America.

Vertex 在第一季錄得 Incivek 淨營收 2.06 億美元。我們預期 Incivek 在 2013 年全年仍將維持市場領先療法地位。然而，自去年第二季以來，美國開始接受治療的 C 型肝炎患者人數一直在下降，而此趨勢很可能在美國持續。在美國以外，Janssen 以 Incivo 的品牌行銷 Telaprevir，而 Vertex 可收取權利金。Incivo 的可得性持續擴展至更多國家；根據 Janssen 於 2013 年第一季的銷售，Vertex 賺取了 3,900 萬美元的權利金。Janssen 將第一季 Incivo 的強勁表現歸因於 Incivo 在拉丁美洲持續且成功的上市推廣。

Moving now to Kalydeco. We launched Kalydeco in the US in early 2012 for cystic fibrosis patients with the G551D mutation, age six and older, and we saw rapid adoption amongst US patients. By the end of 2012, we were treating the vast majority of the eligible G551D patients in the US. For the first quarter of 2013, we achieved US sales of Kalydeco of approximately $50 million, in line with our US sales in the fourth quarter of 2012.

接下來談 Kalydeco。我們於 2012 年初在美國推出 Kalydeco，適用於帶有 G551D 突變、年滿六歲及以上的囊性纖維化患者，並在美國患者中看到快速採用。截至 2012 年底，我們已為美國絕大多數符合資格的 G551D 患者提供治療。2013 年第一季，我們達成 Kalydeco 美國銷售約 5,000 萬美元，與 2012 年第四季的美國銷售大致一致。

In the European union, Kalydeco was approved in July of 2012 and since then, our key objective has been to complete the reimbursement process in the major markets so that we can make Kalydeco available to the patients who need it. It we forecasted growth for Kalydeco in 2013, which reflected our expectation regarding the timing of achieving reimbursement and the speed of uptake in the region.

在歐盟，Kalydeco 於 2012 年 7 月獲准；自那時起，我們的主要目標是完成主要市場的給付（報銷）流程，以便讓有需要的患者能取得 Kalydeco。我們先前對 2013 年 Kalydeco 的成長作出預測，該預測反映了我們對取得給付的時點以及該地區採用速度的預期。

We achieved approximately $12 million in Kalydeco sales outside of the US in the first quarter, which represents reasonable growth over Q4 2012. However, we expect this to accelerate in Q2 2013, given the progress we have made in achieving reimbursement approval in the major European countries. Specifically, in these major market, Kalydeco began to be available in Q1 with commercial reimbursement starting in Q2. The uptake in these markets has been strong, which reinforces our confidence in the growth we can achieve for Kalydeco revenues in 2013.

第一季我們在美國以外地區達成約 1,200 萬美元的 Kalydeco 銷售，較 2012 年第四季呈現合理成長。然而，鑑於我們在主要歐洲國家取得給付核准方面的進展，我們預期 2013 年第二季將加速成長。具體而言，在這些主要市場，Kalydeco 於第一季開始供應，商業給付自第二季開始。這些市場的採用情況強勁，進一步強化我們對 2013 年 Kalydeco 營收可達成成長的信心。

In summary, I'm pleased with Incivek's performance within the hep C market and in the ongoing launch of Kalydeco.

總結來說，我對 Incivek 在 C 肝市場中的表現，以及 Kalydeco 持續上市推進的進展感到滿意。

And now, I will turn it over to Ian.

接下來我把時間交給 Ian。

Thank you, Stuart.

謝謝你，Stuart。

I will start by reaffirming our business and financial strategy, that is, we are investing in the advancement of important medicines that, if successful, will drive sustained long-term business and financial growth. From a financial perspective, our goal during this period is to maintain financial strength. Stated simply, protect our balance sheet by prioritizing our spend toward R&D and balancing our expenses with revenues.

我先重申我們的業務與財務策略：我們正投資於推進重要藥物的研發；若能成功，將帶動長期且可持續的業務與財務成長。從財務角度來看，我們在此期間的目標是維持財務穩健。簡而言之，透過將支出優先配置於研發（R&D），並使費用與營收相平衡，以保護我們的資產負債表。

Now, to the first quarter 2013 results. Total revenues were $328 million. Our total non-GAAP operating expenses, excluding cost of revenues and other charges, were $275 million, and we had a non-GAAP profit of $5.7 million. From a balance sheet perspective, we completed the quarter with approximately $1.24 billion of cash, cash equivalents and marketable securities, and $400 million of 2015 convertible debt outstanding. This debt has early conversion features based on certain stock prices. These results are consistent with our strategy of maintaining our financial strength while progressing our medicines in development.

接著說明 2013 年第一季業績。總營收為 3.28 億美元。我們的非 GAAP 營業費用總額（不含營收成本及其他費用）為 2.75 億美元，非 GAAP 利潤為 570 萬美元。就資產負債表而言，本季末我們持有約 12.4 億美元的現金、約當現金與有價證券，並有 4 億美元的 2015 年到期可轉換債務未償還。該債務包含基於特定股價的提前轉換條款。這些結果與我們在推進研發中藥物的同時維持財務穩健的策略一致。

Now, to the more detailed results. In the first quarter, Kalydeco revenues were approximately $62 million, approximately $50 million in the US and $12 million outside the US. Uptake in early 2013 has been strong in key countries outside the US, and this uptake provides us with the visibility into total Kalydeco revenues for the remainder of 2013. For this reason, we are increasing Kalydeco revenue guidance today.

接下來是更詳細的結果。第一季 Kalydeco 營收約 6,200 萬美元，其中美國約 5,000 萬美元、美國以外約 1,200 萬美元。2013 年初在美國以外的關鍵國家採用情況強勁，這讓我們對 2013 年剩餘期間的 Kalydeco 總營收有更高的能見度。因此，我們今天上調 Kalydeco 的營收指引。

Incivek revenues in the first quarter were $206 million, reflecting continued demand for hepatitis C treatment, even as the market anticipates the arrival of other regimens beginning in 2014. Incivo royalties were $39 million and combined with Incivek revenues, we continue to anticipate significant HCV revenue contributions to our top line in 2013. Finally, collaborative and other revenues in the first quarter were $22 million, bringing total 2013 quarter revenues to $328 million.

第一季 Incivek 營收為 2.06 億美元，反映出在市場預期自 2014 年起將有其他療法方案問世之際，C 型肝炎治療需求仍持續存在。Incivo 權利金為 3,900 萬美元；結合 Incivek 營收，我們仍預期 2013 年 HCV 將對我們的營收（top line）作出顯著貢獻。最後，第一季合作及其他營收為 2,200 萬美元，使 2013 年第一季總營收達到 3.28 億美元。

Now, to the non-GAAP operating expenses of $275 million which excludes cost of revenues and other charges. This is similar to prior year. Within our first quarter 2013 non-GAAP operating expenses, there has been a significant decrease in SG&A comparison to our fourth quarter 2012 and also comparison to the first quarter of 2012 while we continue to prioritize our investments into R&D. In particular, our late stage development investment into our programs for CF, HCV and autoimmune disease programs increased our R&D investment compared to prior year.

接著談非 GAAP 營業費用 2.75 億美元（不含營收成本及其他費用）。此水準與前一年相近。在 2013 年第一季的非 GAAP 營業費用中，與 2012 年第四季以及 2012 年第一季相比，SG&A 顯著下降，同時我們仍持續將投資優先配置於研發。特別是，我們對囊性纖維化（CF）、HCV 以及自體免疫疾病等計畫的後期開發投資，帶動研發投入較前一年增加。

Before I move to our 2013 financial guidance, I would like to provide a comment on our GAAP net loss of $308 million. That includes a charge of $412.9 million for the impairment of our HCV asset, VX222. At this stage of development of our portfolio of HCV assets and given the progression of other regimens by other companies, we are unable to support the fair value of VX222 on our balance sheet and accordingly, we are taking a writedown in the value of this intangible asset. We also recorded a tax benefit for VX222 of $127.6 million. Results in a net charge of $285 million.

在我進入 2013 年財務指引之前，我想先就我們 GAAP 淨損 3.08 億美元補充說明。其中包含針對我們的 HCV 資產 VX222 計提 4.129 億美元的減損費用。在我們 HCV 資產組合目前的研發階段，並考量其他公司推進的其他療法方案進展，我們無法支持在資產負債表上對 VX222 的公允價值評估，因此我們對該無形資產價值進行減記。我們亦就 VX222 認列 1.276 億美元的稅務利益。合計形成 2.85 億美元的淨費用。

Now, to the 2013 financial guidance. Today, we are reiterating our total revenue guidance of $1.1 billion to $1.25 billion that we provided in February 2013. While we are increasing the Kalydeco components of revenues to $300 million to $340 million from $280 million to $320 million we gave previously. Today, we are also reiterating our non-GAAP operating expense of $1.09 billion to $1.15 billion. In summary, financially, we're executing on our strategy and prioritizing investment within our Business to drive long-term growth.

接下來是 2013 年財務指引。今天，我們重申 2013 年 2 月提供的總營收指引：11 億至 12.5 億美元。同時，我們將 Kalydeco 的營收組成上調至 3 億至 3.4 億美元，先前為 2.8 億至 3.2 億美元。今天我們也重申非 GAAP 營業費用為 10.9 億至 11.5 億美元。總結而言，在財務面，我們正落實既定策略，並在公司內部優先配置投資，以推動長期成長。

I would now like to open up the line to questions.

接下來我想開放電話線供提問。

Thank you.

謝謝。

(Operator Instructions)

(接線員指示)

Our first question comes from Geoffrey Porges of Bernstein. Your line is open.

我們的第一個問題來自 Bernstein 的 Geoffrey Porges。您的線路已開通。

Thanks very much for taking the question, and I think the first time on a Vertex call I have been able to congratulate you on saving expenses.

非常感謝讓我提問；我想這是我第一次在 Vertex 的電話會議上能夠恭喜你們節省了費用。

So, my first question is, is this SG&A run rate sustainable at this level after you pulled back on HCV? But if you're successful with expanding NCF, would you anticipate that going back up to the prior level, or is this the sort of thing that we should be forecasting going forward?

所以，我的第一個問題是，在你們縮減 HCV 之後，這個 SG&A 的執行率在目前這個水準是否可持續？但如果你們成功擴大 NCF，你們是否預期會回升到先前的水準，還是說這就是我們往後應該用來預測的水準？

And then I just wanted to get someone's perspective on what was presented over the weekend at Amsterdam. And it wasn't a formal investor event, but has this changed how you look to partnering VX135? And I'm thinking particularly about some of the issues that have come up, for example, with Telaprevir and the pre-existing resistant mutation. Do you think you should be looking elsewhere for further combination studies as a result of that? Thanks.

另外，我也想聽聽大家對於週末在阿姆斯特丹所呈現內容的看法。那不是正式的投資人活動，但這是否改變了你們對 VX135 尋求合作夥伴的看法？我特別想到一些已經浮現的議題，例如 Telaprevir 以及既存的抗藥性突變。你們是否認為因此應該轉向其他方向，去做更多的聯合用藥研究？謝謝。

Geoff, we will take the HCV and [easel] question strategy first, and Jeff will take that.

Geoff，我們先回答 HCV 和 [easel] 的策略問題，這部分由 Jeff 來回答。

Geoff, let me take the strategy question, and then I will turn it over to Bob for the more detailed scientific question around resistance mutants. I think you know, our strategy all along has been to combine VX135 with multiple other DAAs and actually collect the data in phase II that we think will allow us to pick the best regimen or regimens to take forward into pivotal development next year. And I think the results we saw at easel really only reaffirmed our confidence in that strategy.

Geoff，我先回答策略面的問題，接著我會把更細的、關於抗藥性突變的科學問題交給 Bob。我想你知道，我們一路以來的策略都是把 VX135 與多種其他 DAA 併用，並且在第二期試驗中收集我們認為能讓我們挑選最佳療程（或多個療程）的資料，以便明年推進到關鍵性開發。而我認為我們在 easel 看到的結果，只是再次確認了我們對這個策略的信心。

So, as we discussed today, we have multiple partnerships in which we can look at 135 with ribavirin and at least three other DAAs, and it is our plan to continue that strategy going forward. I think at the end of the day, the data will really speak to this, but I think the picture is becoming pretty clear that a nuke will be the backbone of most of these straightforward DAA regimens, and we think VX135 is competitive with any nuke out there.

因此，如同我們今天討論的，我們有多個合作夥伴關係，可以評估 135 與 ribavirin 以及至少三種其他 DAA 的併用，而我們的計畫是持續推進這個策略。我想最終還是要看數據怎麼說，但目前看起來相當清楚：在多數這些相對直接的 DAA 療程中，核苷（nuke）會是骨幹，而我們認為 VX135 與市面上任何核苷藥物相比都具競爭力。

So, let me turn this over to Bob for your specific question.

那我把你的具體問題交給 Bob。

Hi, Geoff, this is Bob.

嗨，Geoff，我是 Bob。

Hi, Bob.

嗨，Bob。

So, with specific reference to the Q80 var -- baseline variant, we are aware of those data. In the two studies, two phase III studies they reported, there appeared to be some decrement in SVR in the patients with those variants at baseline. It wasn't dramatic, but probably there was some decline.

就你特別提到的 Q80 變異——基線變異而言，我們知道那些數據。在他們報告的兩項研究、兩項第三期研究中，基線帶有這些變異的病人，其 SVR 似乎有些下降。幅度不算大，但可能確實有些下滑。

On the other hand, in combination with the nuke, it may well not really be a clinical issue. And obviously, that is something we will evaluate in the initial studies. But it certainly doesn't change our strategy of working with Simeprevir as part of our combination regimens.

但另一方面，若與核苷藥物併用，這很可能不會真正成為臨床上的問題。而且很明顯，這也是我們會在初期研究中評估的事情。但這當然不會改變我們把 Simeprevir 納入我們聯合療程的一部分、並與之合作的策略。

Right, thanks. And Ian, on the SG&A?

好的，謝謝。Ian，關於 SG&A 呢？

Yes, and Geoff, thanks for that. I will just kind of bring you to the broader picture. Back in February, we did give OpEx guidance, total non-GAAP OpEx guidance of 1.09 to 1.15. We are reiterating that today.

好的，Geoff，謝謝你的問題。我先把你帶到更宏觀的脈絡來看。回到二月，我們曾提供 OpEx 指引，也就是非 GAAP 的總 OpEx 指引為 10.9 億到 11.5 億。我們今天重申這個指引。

The number that you point to, though, the SG&A expenses where we're approximately $80 million for Q1, I can see what you're doing, you're taking that and multiplying it by four and saying that may be just under the guidance we gave of 3.40 to 3.60. We are still reiterating the 3.40 to 3.60; we still are launching a, what we believe is an important drug and still expanding into Europe, and so there are marketing expenses that go along with that. So, we're reiterating the components of our guidance today as well, and that SG&A component we see 3.40 to 3.60.

不過你指出的那個數字——第一季 SG&A 費用大約 8,000 萬美元——我理解你的算法：把它乘以四，然後說可能會略低於我們給的 34 億到 36 億的指引。我們仍然重申 34 億到 36 億；我們仍在推出一款我們認為很重要的藥物，並且仍在擴展到歐洲，因此會有相應的行銷費用。所以，我們今天也重申指引的各個組成部分，而 SG&A 這一項我們仍然看 34 億到 36 億。

Okay, thanks.

好的，謝謝。

Thank you. Our next question comes from Geoff Meacham of JPMorgan. Your line is open.

謝謝。我們下一個問題來自 JPMorgan 的 Geoff Meacham。你的線路已開通。

Thanks for taking the question. I got a CF one and then an RA one.

謝謝讓我提問。我有一個 CF 的問題，然後一個 RA 的問題。

I want to get a sense from you on the Kalydeco monotherapy trials, the G117H and then G551D in younger patients. It has been ongoing for a while, so is it that the entry criteria are narrow, or is it a matter of just finding patients? I would have thought that these would have enrolled fairly quickly, given the visibility and the clinical effect in the STRIVE study.

我想了解你們對 Kalydeco 單藥試驗的看法，包括 G117H，以及在更年幼病人中的 G551D。這些試驗已進行一段時間了，所以是因為入組標準很窄，還是只是找病人的問題？考量到 STRIVE 研究的能見度與臨床效果，我原本以為這些應該會很快完成收案。

This is Bob. For the non-G551D gating, that study is fully enrolled, so that one is well underway.

我是 Bob。針對非 G551D 的 gating（門控）突變，那項研究已經完成收案，所以進展很順利、也已在進行中。

The R117H study is still enrolling, although it is well along in its progress. And that, I think, is just a combination of it is still a pretty uncommon mutation, and so finding patients who meet the entry criteria is -- it just takes time. But I think we're making good progress there, and we expect enrollment to be finished sometime soon.

R117H 的研究仍在收案中，不過進度已相當靠前。我想這只是因為這仍是相當罕見的突變，因此要找到符合入組標準的病人——確實需要時間。但我認為我們進展良好，並預期收案會在不久後完成。

And Geoff, I would just add, there is the other study that it in the other gating mutations, which has completed enrollment and we anticipate seeing the first data from that from the second half of this year.

Geoff，我再補充一下，還有另一項針對其他 gating 突變的研究，已完成收案，我們預期今年下半年會看到該研究的第一批數據。

And in terms of the kids that you are referring to, I think you have to go through a global process that has the pip process in there in Europe, which is quite a lengthy process, which now is finalized and now we are ready to go.

至於你提到的兒童族群，我想你必須走一個全球性的流程，其中在歐洲包含 PIP 流程，這是相當冗長的程序；目前已經完成定案，我們也已準備就緒。

Got you. Okay, and just a follow-up -- or a second question on VX509, I know you guys have talked about partnering this out. And maybe to Jeff's perspective, given his background, is there a data set or an efficacy benchmark that you would reconsider that from a development perspective, to take it on your own? Or is that going to be 100% partnering or bust?

了解。好的，另外追問——或第二個問題，關於 VX509，我知道你們談過要把它對外尋求合作。也許請 Jeff 從他的背景角度來看，是否存在某一組數據或某個療效基準，會讓你們從開發角度重新考慮、改為自己主導開發？還是說這會是 100% 只能合作，否則就不做？

Geoff, thanks for asking the question. I think as we've looked at what it takes to develop this asset and multiple indications and multiple geographies, which I think is what is going to be needed to be competitive, that is really a process that we feel comfortable with only in a partnership. So, that really is our plan going forward.

Geoff，謝謝你的提問。我們在評估開發這個資產所需的投入時，考量到多個適應症與多個地理市場——我認為要具競爭力就必須如此——我們覺得只有在合作夥伴關係下，我們才有把握推進這個流程。所以，這確實是我們接下來的計畫。

Got you, okay. Thanks.

了解，好的。謝謝。

Thank you. Our next question comes from Michael Yee of RBC Capital. Your line is open.

謝謝。我們下一個問題來自 RBC Capital 的 Michael Yee。你的線路已開通。

Yes, hey, thanks. On a question on hep C, obviously you are going to get presumably some Bristol/Vertex combination data sooner than the others. And obviously, I think we can all see what a nuke in NS5A has done out there with other collaborations. Time is of the essence and the other studies may take longer.

是的，嗨，謝謝。關於丙肝的一個問題：很明顯你們應該會比其他合作更早拿到一些 Bristol/Vertex 的聯合用藥數據。而且我想大家都看得出來，在其他合作中，核苷藥物搭配 NS5A 已經展現了什麼樣的效果。時間非常關鍵，而其他研究可能需要更久。

If the data looks really good, why would we wait? Maybe you can walk through some of the strategy and timing of that as you think about that end of this year, going into 2014. And then second question is just on the CF809 phase III studies, would you expect this to enroll faster than the Kalydeco studies, given there are definitely a lot more patients out there than G551? Thanks.

如果數據看起來真的很好，為什麼我們要等？也許你可以在你思考今年年底、進入2014年時，帶我們走一遍其中的一些策略與時程安排。然後第二個問題是關於CF809的第三期研究，你是否預期其收案速度會比Kalydeco研究更快，因為外面確實有比G551更多的病人？謝謝。

Michael, this Jeff. Let me take your first question and then maybe I will turn it over to Bob for your question on the CF enrollment. With respect to the timing of these different studies on VX135, just to be clear, we're not necessarily going to wait. We agree with you that speed is of the essence here, and we hope to begin collecting data, actually, as soon as the third quarter of this year, with some combinations, like the ribavirin study, and then subsequently with the others.

Michael，我是Jeff。我先回答你的第一個問題，然後也許我會把你關於CF收案的問題交給Bob。就VX135這些不同研究的時程而言，先說清楚，我們不一定會等待。我們同意你所說的，速度在這裡至關重要；我們希望能儘快開始收集數據，實際上，最早在今年第三季就能在某些組合上開始，例如利巴韋林（ribavirin）研究，之後再進行其他組合。

And as you say, if we saw a combination that was clearly a winning combination or an ultra competitive combination, we wouldn't wait to move it forward. Because we agree that we want to go as quickly as possible to patients.

而且如你所說，如果我們看到某個組合明顯是勝出組合或是極具競爭力的組合，我們不會等著才推進。因為我們同意，我們希望盡可能快地把治療帶給病人。

Okay.

好的。

And then your other question?

那你另一個問題呢？

Speed of the 809 enrollment verse Kalydeco, yes.

809的收案速度相較於Kalydeco，是的。

Yes, we haven't really given any information on how quickly we expect to enroll. I think they will be rapid. The patients are highly interested.

是的，我們其實還沒有提供任何關於我們預期收案速度有多快的資訊。我認為會很快。病人非常有興趣。

In general, first of all, we are recruiting a lot more patients into these two trials than we did with the Kalydeco study, so that will be a factor. And the other is that site startup tends to be more of a limiting factor in some respects than actual patient recruitment. Once the sites are up and running, they tend to recruit very quickly. And we're obviously doing as fast as we can to get the sites up and running, but that tends to be to more rate limiting step.

一般來說，首先，我們在這兩項試驗中要招募的病人數比Kalydeco研究多得多，所以這會是一個因素。另外，在某些方面，研究中心啟動（site startup）往往比實際病人招募更具限制性。一旦研究中心啟動並運作，通常收案會非常快。我們當然會盡可能快地讓研究中心啟動並運作，但那往往是更具速率限制的步驟。

Michael, we will probably have a better understanding of speed of enrollment when we're on our July quarterly conference call, and maybe we will give some comments at that time.

Michael，我們可能會在7月的季度電話會議時，對收案速度有更好的掌握，也許到時候我們會做一些評論。

Okay, perfect. Thank you.

好的，太好了。謝謝。

Our next question comes from Rachel McMinn of Merrill Lynch. Your line is open.

我們的下一個問題來自美林（Merrill Lynch）的Rachel McMinn。你的線路已開通。

Yes, thanks very much. I wanted to go back to hep C for a moment and get a patient number. How many patients worth of data do you think you will have by the end of the year when you add all of these studies up? I think safety is the big question that a lot of people have.

是的，非常感謝。我想回到丙肝（hep C）這個話題，問一個病人數的問題。把所有這些研究加總起來，你認為到今年年底你們會有多少名病人的數據？我想安全性是很多人最大的疑問。

And then also wanted to get your perspective on heterozygous, when we could see the first studies initiated there. I don't know if that is something that you think is a next step for 661, or we would have to wait until 2014 before you'd consider starting any of those studies.

另外也想請你談談你對雜合子（heterozygous）的看法，我們何時可能看到那邊的第一批研究啟動。我不確定這是否是你認為661的下一步，或是你們要等到2014年才會考慮啟動任何這類研究。

And really quick on a housekeeping question, are there any other commercial CF milestones that we should be thinking about near-term? If you could give us a little bit more color on the structure of how we think about sales-based milestones, that would be helpful for modeling purpose, thanks.

再很快問一個例行性問題，近期還有沒有其他商業化的CF里程碑是我們應該留意的？如果你能多提供一些關於我們如何看待以銷售為基礎的里程碑之結構細節，對建模會很有幫助，謝謝。

So, this is Bob. I will take the safety question. It is a little bit of a hard question to answer because obviously, the studies are ongoing and we will have varying lengths of safety data at any time point toward the end of the year.

我是Bob。我來回答安全性的問題。這有點難回答，因為顯然研究仍在進行中，而在年底任何時間點，我們可取得的安全性數據長度會不一樣。

Well, specifically, 12 weeks, then.

嗯，具體來說，是12週的話呢？

Yes, we will have 12-weekday data, probably on the order of 40 to 50, maybe 60 patients by then.

是的，屆時我們會有12週的數據，大概是40到50名病人，可能到60名左右。

And is that really enough to go into phase III then, Bob?

那樣就足以進入第三期了嗎，Bob？

Not necessarily at that point, but we will be expanding these studies and starting additional trials so that we will be augmenting that safety database through the end of 2013 into early 2014 in order to get enough patients to go into phase III.

不一定在那個時間點就足夠，但我們會擴大這些研究並啟動額外試驗，因此我們會在2013年底到2014年初持續擴充安全性資料庫，以取得足夠的病人數來進入第三期。

Rachel, just on your question that you asked, you did specifically mark it to the end of the year. But the way these studies progress is we do start the smaller study and expect to expand that study in the second half of this year. So, as you look, as we go into 2014 and through 2014, we continue to accumulate patient experience.

Rachel，關於你問的問題，你確實是特別以年底為時間點來問。但這些研究的推進方式是：我們先做較小規模的研究，並預期在今年下半年擴大該研究。因此，當你看到我們進入2014年並在2014年期間，我們會持續累積病人使用經驗。

That is why we have made the statement we believe we will be in pivotal development to do that in 2014. It is not from the initial study and it is not marked from the patients at the end of this year, but it's as we go into 2014, we will have accumulated more patients.

這也是為什麼我們說我們相信在2014年會進入關鍵性（pivotal）開發。這不是基於初始研究，也不是以今年年底的病人數作為標記；而是當我們進入2014年時，我們將累積更多病人。

And finally, Rachel, your question on the heterozygous, this is Jeff, we are considering with regulatory authorities how to approach the heterozygous. We have a couple of different approaches. I think it is too early for us to give you specific plans.

最後，Rachel，你關於雜合子（heterozygous）的問題，我是Jeff。我們正在與監管機關討論要如何切入雜合子族群。我們有幾種不同的做法。我想現在還太早，無法提供具體計畫。

But we are formulating plans, both with our current correctors, as we've said. But also with combination with second generation correctors, and we want to move as quickly as we can to that population of patients.

但我們正在擬定計畫，正如我們所說，會使用我們目前的校正劑（correctors）。同時也會與第二代校正劑的組合一起規劃，我們希望能盡可能快地推進到那一群病人。

And to your financial question, Rachel, to the milestone payments, we did make a payment of approximately $9.5 million this quarter, or the first quarter, in connection with our CF revenues. There are future milestones, but we will disclose those as we achieve them based on certain sales levels.

至於你的財務問題，Rachel，關於里程碑款項，我們本季（第一季）已就我們的CF營收支付了約950萬美元。未來還有其他里程碑，但我們會在達到特定銷售水準並實現時再予以揭露。

Okay. Thank you.

好的。謝謝。

Our next question comes from Mark Schoenebaum of ISI Group. Your line is open.

我們的下一個問題來自ISI Group的Mark Schoenebaum。你的線路已開通。

Hey, guys. Thanks a lot for taking the question. I have two pretty simple ones.

嗨，各位。非常感謝讓我提問。我有兩個相當簡單的問題。

One, the first one, would it be possible for you to -- and maybe you have answered this and I just don't know, but would it be possible for to you tell us where the IP is down filed for Kalydeco 809 and 661. And where you will be manufacturing those three drugs?

第一個，你們是否可以——也許你們已經回答過而我不知道——但你們是否可以告訴我們Kalydeco、809和661的智慧財產權（IP）是在哪裡提交申請的？以及你們將在哪裡製造這三種藥物？

The second question is a hep C market question. Do you guys, would you happen to have the following number, the number -- roughly the number of hepatitis C patients today? If you have genotype 1, that's fine, but the number of hepatitis C patients today who you think are under the active care of an HCV treating specialist? Thank you very much.

第二個問題是丙肝市場的問題。你們是否剛好有以下這個數字：目前大約有多少名丙型肝炎病人？如果你們有基因型1也可以，但我想問的是：你們認為目前有多少名丙肝病人是在接受HCV治療專科醫師的積極照護之下？非常感謝。

Thanks, Mark for the question. I will take the tax question. And what I would say is, we've taken all of the appropriate tax planning steps. We believe there is a lot of value in our CF franchise, and we believe that we are going to be global with the franchise.

謝謝你，Mark，謝謝你的問題。我來回答稅務問題。我想說的是，我們已採取所有適當的稅務規劃步驟。我們相信我們的CF產品線具有很高的價值，而且我們相信我們會把這個產品線推向全球。

So, we have taken all of the appropriate tax steps at this point in time that a company should take. And -- but to project out a tax rate at this point in time, I think it is a little too early. I think as we get close to profit, then we would be happy to start giving you some guidance towards that. But you can expect that the tax structuring for the Company, we're taking appropriate tax steps.

因此，就目前這個時間點而言，我們已採取公司應採取的所有適當稅務措施。但是——要在此時此刻推估稅率，我認為還稍嫌過早。我想等我們接近獲利時，我們會很樂意開始就此提供一些指引。但你可以預期，公司在稅務架構方面，我們正在採取適當的稅務步驟。

Can you can tell us where you will be making it?

你能告訴我們你們會在哪裡認列（獲利/收入）嗎？

It's -- no, not at this point.

這個——不，目前還不能。

Okay.

好的。

It is actually less relevant to where it is being made.

實際上，在哪裡認列並沒有那麼相關。

Okay.

好的。

The other point I would point out, just because you are asking about tax, I think it is also important to note that Vertex has approximately $3.5 billion of NOLs that do get offset against profits before you start paying cash taxes. So, that will clearly benefit our cash flow in the early years of profitability. And to your other questions --

另外一點我想指出，既然你在問稅務，我也認為很重要的是要注意，Vertex 約有 35 億美元的淨營運虧損（NOL），在你開始支付現金稅之前，這些可以用來抵減獲利。因此，這在我們獲利初期的年度，顯然會有利於現金流。至於你其他的問題——

Yes, Mark, we will have to get back to you on that.

是的，Mark，這個我們得再回覆你。

Okay, no problem. Thanks a lot, guys. I appreciate it.

好的，沒問題。非常感謝，各位。我很感激。

I can't give it to you off the top of my head.

我一時之間想不起來。

The next question is from Yaron Weber of Citi. Your line is open.

下一個問題來自花旗（Citi）的 Yaron Weber。您的線路已開通。

Great. Thanks for taking my questions. So, I just have a few questions, a little bit all over the place.

很好。謝謝讓我提問。我有幾個問題，範圍有點分散。

But just starting with 135, just as a follow-up to a previous question, so it will be for Bob. So Bob, it sounds like you are going to have 40 to 60 patients by the end of the year, safety, that is going to be the preliminary 12 weeks of safety that you need to do with the preliminary experience, with 135, with another agent. So, at some point during the year, are you going to enroll that into, or broaden that into an expanded sort of cohort that is going to have probably, I would imagine 100 or 200-plus patients.

不過先從 135 開始，作為對先前問題的追問，這題是給 Bob 的。Bob，聽起來你們到年底會有 40 到 60 名病患，安全性方面，這會是你們需要做的初步 12 週安全性資料，基於 135 與另一個藥物併用的初步經驗。那麼在今年某個時間點，你們是否會把它納入、或擴大成一個更大的擴展型隊列？我猜可能會有 100 或 200 名以上的病患。

Any sense, when are you going to have the 12-week safety from that, because that is going to be really gate laboring to starting phase III? So, that is going to be the first question, then I have a follow-up.

你們大概何時會拿到那個隊列的 12 週安全性資料？因為那將是啟動第三期的關鍵門檻。這是第一個問題，接著我還有追問。

So, I think you can add up the timing, it will probably be in the, certainly in the first half of 2014, that we will have that information and expect to take that to regulatory agencies to gain approval for the pivotal program.

我想你可以推算時程，我們大概會在 2014 年上半年、確切說肯定在上半年取得那些資訊，並預期把它提交給監管機構，以取得關鍵性（pivotal）計畫的核准。

Because one of the things that I'm trying to understand a little bit is the key to you to -- and do you think it is relevant that -- I would imagine you guys need to and want to be in phase III before potentially Avery, and then Gilead going to be out there with their all-oral regimen, because that could signify a change in care. Is that something that you agree with, or no?

因為我想更了解的一點是，對你們而言的關鍵在於——你是否認為這點很相關：我想你們需要、也希望在第三期上比 Avery（可能）更早，然後 Gilead 也會推出他們的全口服療法，因為那可能代表照護方式的改變。你同意這樣的看法嗎？還是不同意？

I agree with that, and that is our strategy.

我同意，而這就是我們的策略。

Okay. Second question, just on -- thank you for that. Kalydeco, the $12 million OUS, can you give us a little bit of a sense, how much of that was in Scotland? And I'm trying to see, did you get anything at all in the UK, and I imagine Ireland was on board. I'm trying to get a sense, that $12 million, which countries were on board already.

好的。第二個問題，謝謝你剛才的回答。關於 Kalydeco，海外（OUS）的 1,200 萬美元，你能否讓我們大概了解其中有多少來自蘇格蘭？我想確認一下，你們在英國是否已經有任何收入？我猜愛爾蘭已經納入給付。我想了解那 1,200 萬美元目前是哪些國家已經上線。

Yes, so reimbursement in most of the US and Ireland didn't kick in right until the back end of Q1 and at the beginning of Q2. So, the majority of the $12 million, the majority of the growth over Q4 was from existing markets like Germany, where we're already on the market and reimbursed. We are really expecting the growth in the UK to come in Q2 and beyond.

是的，所以在多數（市場）的給付，以及愛爾蘭的給付，直到第一季末段與第二季初才開始生效。因此，那 1,200 萬美元中的大部分、以及相較第四季的成長，大多來自既有市場，例如德國，我們已經上市且已獲給付。我們確實預期英國的成長會在第二季及之後出現。

Okay. And do you see any growth at all coming up in the US at the moment? Or do you really need to -- do we need to really wait for new mutations to really expand the market here?

好的。那你們目前在美國有看到任何成長嗎？還是說，我們真的得等到新的突變型適應症，才能在這裡擴大市場？

Yes, I would agree with that. We've said a number of times, the vast majority of G551D patients over six in the US have already been receiving treatment. So really, what is going to lead to growth in the US is those new indications that we're working on with Ivacaftor in monotherapy.

是的，我同意。我們已多次提到，在美國，絕大多數 6 歲以上的 G551D 病患都已經在接受治療。所以，真正會帶動美國成長的，是我們正在推進的 Ivacaftor 單藥治療所帶來的新適應症。

Great. And just a final question, and thanks for bearing with these questions. Does the CF Foundation get royalties from minus and 661 and 809? Thank you.

很好。最後一個問題，謝謝你們耐心回答。CF Foundation 是否會從 minus、661 和 809 取得權利金？謝謝。

We haven't disclosed whether royalties are actually paid. But we will at a future point later in development.

我們尚未揭露是否實際支付權利金。但在未來、在研發進展到某個階段時，我們會披露。

Okay. Thank you.

好的。謝謝。

Our next question comes from Lisa Bayko of JMP Securities. Your line is open.

下一個問題來自 JMP Securities 的 Lisa Bayko。您的線路已開通。

Hi, thanks for taking the question. I just wanted to verify what is the nature of the data you will be presenting at the upcoming European cystic fibrosis foundation, or cystic fibrosis conference? And then a quick question on your intentions for the convert. Thank you.

嗨，謝謝讓我提問。我想確認一下，你們即將在歐洲囊性纖維化基金會（European cystic fibrosis foundation）或囊性纖維化會議上，將發表的資料性質是什麼？另外快速問一下你們對可轉債（convert）的規劃。謝謝。

Thanks, Lisa. Well, as usual, we don't get ahead of data that that would be -- data and presentations that would be accepted at these major medical conversations, so we will be advising you of that at a future point in time. As far as the debt is concerned, we have $400 million of 2015 convertible debt. It does have provisional call features. It has a hard call provisional call after October 2013, that if the stock trades above $48, then we can call the debt.

謝謝你，Lisa。嗯，一如往常，我們不會在這些重要醫學會議所接受的資料與簡報正式公布前就先行透露，所以我們會在未來某個時間點再向你們說明。至於債務方面，我們有 4 億美元、2015 年到期的可轉換公司債。它包含臨時（provisional）的提前贖回條款。在 2013 年 10 月之後有一個硬性（hard call）的臨時贖回條款：若股價交易高於 48 美元，我們就可以召回（call）該債務。

And it also has a soft call feature. Sometimes people aren't aware of that. But it does have a soft call feature that if the debt trades just above $63 for 20 days out of 30, then we do have the opportunity and will have the intent to convert it into equity.

它也有一個軟性（soft call）條款。有時候大家不一定知道這點。但它確實有軟性贖回條款：如果該債券價格在 30 天中有 20 天交易在略高於 63 美元，那麼我們就有機會、也有意圖將其轉換為股權。

So, we are happy with maybe having that opportunity in the near future to convert the debt into equity, which is all consistent with the broad financial strategy of managing the P&L that the revenues to the operating expense and then managing the cash on the balance sheet, and also managing the debt on the balance sheet.

因此，我們樂見在不久的將來可能有機會把債務轉換為股權；這也完全符合我們整體的財務策略：管理損益表（P&L）上營收與營運費用的關係、管理資產負債表上的現金，同時也管理資產負債表上的負債。

Thanks a lot.

非常感謝。

Our next question comes from Brian Abrahams of Wells Fargo Securities. Your line is open.

下一個問題來自富國證券（Wells Fargo Securities）的 Brian Abrahams。您的線路已開通。

Hi, thanks for taking my question. You presented a lot of preclinical tox work that you had done on 135 relative to other molecules. I'm just wondering if you can give us a sense as to maybe how comfortable the FDA is with this idea that it is the interaction with my mitochondrial DNA that caused the tox for other nukes, which obviously you guys have less of with the 135.

嗨，謝謝讓我提問。你們展示了相較於其他分子，針對 135 所做的大量臨床前毒理（tox）研究。我想請教你們能否讓我們了解一下，FDA 對於「其他核苷類（nukes）的毒性是由其與粒線體 DNA 的交互作用所造成」這個觀點的接受度有多高；而顯然在 135 上你們看到的這類交互作用要少得多。

Is there any other preclinical work that you might be able to do in parallel to enable yourself to move even more quickly through the clinic, or is the rate limit expect here just combo PK rather than just FDA? Thanks.

另外，是否還有任何其他可以同步進行的臨床前工作，讓你們能在臨床上推進得更快？還是說這裡的速率限制主要預期會是聯合用藥的藥物動力學（combo PK），而不只是 FDA 的要求？謝謝。

So Brian, it's Peter speaking. With respect to the agency, we had quite intense discussion about the safety profile of 135 alone and in combination with potential other agents. And I think we, from a tox point of view, satisfied their needs. I think there that is no additional tox status that we will do.

Brian，我是 Peter。就主管機關而言，我們就 135 單藥以及與其他潛在藥物併用的安全性概況，進行了相當密集的討論。我認為從毒理角度來看，我們已滿足他們的需求。我想在這方面我們不會再做額外的毒理研究。

And from a clinical point of view, we agreed to a cautious forward program, that if successful, will then basically open up toward enrollment as we go forward. So, I think with everything accepted, I think there is no more that we have to do.

而從臨床角度來看，我們同意採取一個審慎的前進方案；若成功，基本上就會在推進過程中逐步開放納入受試者。所以，我認為在一切都已獲接受的情況下，我們沒有更多必須要做的事。

Thanks very much.

非常感謝。

Our next question comes from Robyn Karnauskas of George Bank. Your line is open.

下一個問題來自 George Bank 的 Robyn Karnauskas。請發問。

Thanks for taking my question. Just one other question on hep C.

謝謝讓我提問。我還有一個關於丙肝（hep C）的小問題。

Obviously, the J & J time lines have slowed, and you're seeing second quarter for the Bristol study. What gets you more comfortable that you can hit those time lines with Bristol? And maybe more specific question, what steps or interaction needs to be taken before you start the Bristol study?

顯然，J&J 的時程已放慢，而你們也看到 Bristol 的研究會在第二季進行。是什麼讓你們更有把握能在 Bristol 這邊達成那些時程？另外更具體地問，在啟動 Bristol 研究之前，需要採取哪些步驟或進行哪些互動？

This is Bob. Just first of all, there are no drug interaction studies that we're required to do before we start the combination with Daclatasvir. We will just be measures pharmacokinetics of the components in the first small cohort of patients to get started.

我是 Bob。首先，在我們開始與 Daclatasvir 的聯合治療之前，並沒有被要求必須先做任何藥物交互作用研究。我們只會在第一個小型受試者隊列中量測各組成藥物的藥物動力學，以便啟動。

And the J & J time line is really driven by the outcome of the drug interaction studies, which are ongoing. Once we have those data and can confirm the doses we are going to use, we will be raring to go and ready to go into phase II.

而 J&J 的時程其實主要是由正在進行的藥物交互作用研究結果所驅動。一旦我們拿到那些數據並能確認要使用的劑量，我們就會蓄勢待發，準備進入第二期（phase II）。

As a follow-up, do you control the Bristol study or is that really in Bristol's hands?

追問一下，Bristol 的研究是由你們掌控，還是主要在 Bristol 手上？

We're running the Bristol study.

Bristol 的研究是由我們執行。

Okay, great. Thank you.

好的，很棒。謝謝。

Our next question comes from Matt Roden of UBS. Your line is open.

下一個問題來自 UBS 的 Matt Roden。請發問。

Great, thanks for taking the questions. So, Kalydeco in Europe, to get to the lower end of guidance, it looks like we will need to see some greater sequential gains this year than what you had in the first quarter and presumably, that comes from expanded geographies in Europe.

很好，謝謝讓我提問。關於 Kalydeco 在歐洲，若要達到指引（guidance）區間的下緣，看起來今年我們需要看到比第一季更大的逐季成長；而我推測這主要來自歐洲更多地區的擴張。

Can you speak to the line of sight that you have a little bit more specifically as to what regions are going to come on board in the second quarter and thereafter, that is going to enable you to get to the guidance range that you have? And then I have a follow-up on heterozygous, if I may. Thank you.

你能否更具體談談你們目前的可見度（line of sight）：第二季以及之後，哪些地區會陸續加入，從而讓你們能達到你們所給出的指引區間？另外如果可以的話，我還有一個關於異合子（heterozygous）的追問。謝謝。

Sure, Matt, let me talk through. So, in reimbursement terms, which is the key to kind of the accelerating growth that we are projecting, we have achieved reimbursement across the UK and the Republic of Ireland, with the exception of Wales. The notable markets there are England, Scotland and Ireland, which have the largest preponderance of patients.

當然，Matt，我來說明一下。就給付／報銷（reimbursement）而言——這是我們所預期加速成長的關鍵——我們已在英國與愛爾蘭共和國取得給付，威爾斯除外。其中較重要的市場是英格蘭、蘇格蘭與愛爾蘭，這些地區的患者占比最高。

So, them coming on stream, in addition to France and Germany where we already have reimbursements in place, that is what leads us to believe that we can be more sure of the revenue expectations in 2013. And that reimbursement backed up by the reaction we have seen from CF patients in CF centers, and the initial uptake we've seen since reimbursement kicked in, that is what gives us more confidence in the guidance that we are updating today.

因此，這些市場的啟動，加上我們在法國與德國已經取得的給付安排，使我們相信 2013 年的營收預期更具確定性。此外，給付落地後，我們在囊性纖維化（CF）中心看到的 CF 患者反應，以及自給付生效以來觀察到的初期採用情況，也讓我們對今天更新的指引更有信心。

Thanks for that, Stuart. Very helpful. And then on the Heterozygous, we have seen that with the VX809 that the heterozygous data weren't sufficient for moving forward, as you guys talked about.

謝謝你，Stuart。非常有幫助。接著談異合子方面，我們已看到在 VX809 上，異合子數據不足以推進到下一步，正如你們所提到的。

When you think about 983 and 661, presumably you guys mow more about these molecules than we do. Is there anything about those two molecules that give you any confidence or any inkling that they may be more successful than 809 in the heterozygous when combined singly with Kalydeco? And then sort of follow on to that is, ultimately, do you think you are going to need to have a triple combo, that is two correctors in Kalydeco, to get the results that you need in the heterozygous population?

當你們看 983 和 661 時，推測你們對這些分子的了解比我們多。這兩個分子是否有任何特點，讓你們有信心或有任何跡象顯示：它們在與 Kalydeco 單一合併（combined singly）時，可能比 809 在異合子族群中更成功？另外延伸來看，你們最終是否認為需要三聯組合（triple combo）——也就是兩個校正劑（correctors）加上 Kalydeco——才能在異合子族群中達到所需的效果？

Great questions. And so I think as we've said before, we believe from what we know today, and it is still based on a fairly small amount of data, that the heterozygous are going to be more difficult to treat than the homozygous, both from our cell studies and what we've seen, as you point out, with 809 in the clinic.

問題很好。如同我們之前所說，根據我們目前所知——而且仍是基於相對少量的數據——我們相信異合子會比同合子（homozygous）更難治療；這一點不論從我們的細胞研究，或如你所指出在臨床上 809 的結果，都可看出。

We may do some more work with the single correctors, first generation correctors like 661 and 983 that do have different pharmacokinetic and tissue penetration properties. But I do -- if you can me to handicap it today, I think the ultimate solution to the heterozygous will really come from the combination of a first and a second generation corrector with Kalydeco. It's one of the reasons why we are trying to move those second generation correctors forward as quickly as we possibly can.

我們可能會再針對單一校正劑做一些工作，像是第一代校正劑 661 和 983，它們確實具有不同的藥物動力學與組織穿透特性。但如果你要我今天做個判斷（handicap），我認為異合子的最終解方，會是第一代與第二代校正劑再加上 Kalydeco 的組合。這也是我們試圖盡可能快速推進那些第二代校正劑的原因之一。

Thank you very much.

非常感謝。

Thank you.

謝謝。

(Operator Instructions)

（接線員指示）

The next question comes from Ying Huang of Barclays. Your line is open.

下一個問題來自 Barclays 的 Ying Huang。請發問。

Thanks, guys, for taking my questions also. I have one that is, assuming everything else being equal, would you rather have an acquisition of a company where you do have a PI or an (inaudible) in there before you can have everything in the combo under one umbrella? You can get 100% economics, given your stock has appreciated large lately.

謝謝各位也讓我提問。我有一個問題：在其他條件都相同的假設下，你們是否會更傾向於收購一家你們在其中已擁有主要研究者（PI）或（聽不清）相關資產的公司，藉此在同一個架構下把聯合療法（combo）所需的一切都納入？考量到你們股價近期大幅上漲，這樣你們就能取得 100% 的經濟利益（economics）。

And then secondly, on CF, we know that you're pushing already three compounds in the clinic for CFTR correctors. What is your view of the competition? And we know that Novartis has one CFTR [drop off] in phase I as well. What is your strategy, can you elaborate a little bit? Thank you.

第二個問題，關於囊性纖維化（CF）：我們知道你們已經推進三個 CFTR 校正劑化合物進入臨床。你們如何看待競爭態勢？我們也知道 Novartis 也有一個 CFTR（中斷）在第一期（phase I）。你們的策略是什麼？能否再多說一點？謝謝。

I will take the M&A question that you asked, and then Jeff will talk about the CF strategy. First of all, M&A and licensing and other things, they're tactics to the end game. Clearly, if are you in a position where you can control the regimen, it is easier in terms of moving through development and also controlling the commercialization of that regimen.

我先回答你提出的併購（M&A）問題，接著 Jeff 會談 CF 策略。首先，併購、授權以及其他事項，都是為了最終目標所採取的戰術。很明顯地，如果你處於能夠掌控治療方案（regimen）的地位，在推進開發以及掌控該方案的商業化方面都會更容易。

However, I would say at this point in time as we progress forward, you're seeing us execute on the strategy that we think we're looking to create the best regimen of what 135 is in the middle of. And we continue to execute around that and give ourselves multiple chances, and at this point, we are just going to continue along that strategy.

不過，我會說在目前這個時間點，隨著我們持續往前推進，你會看到我們正在執行我們認為的策略，也就是要打造 135 所處核心位置的最佳治療方案。我們會持續圍繞這一點執行，讓自己擁有多次成功的機會；而在此刻，我們就是會沿著這個策略繼續前進。

And then with respect to the CF strategy and the competition, we're in a very fortunate position here that our scientists started working on this problem 14, 15 years ago now and clearly established a leadership position in the science, which is reflected in the portfolio of drugs we have.

至於 CF 策略與競爭，我們在這裡處於非常有利的位置，因為我們的科學家在 14、15 年前就開始研究這個問題，並且很明確地在科學上建立了領先地位，這也反映在我們擁有的藥物組合（portfolio）上。

On the other hand, we fully expect that there will be competition. That's the way this industry always works once someone sees the successes, and we anticipate that. Our strategy is to move as quickly as we can with our portfolio, get those to as many patients as possible to benefit them, and we think in the long run, that is best for patients and best for Vertex.

另一方面，我們完全預期會有競爭出現。一旦有人看到成功，這個產業一向就是這樣運作的，我們也預先考量到了。我們的策略是以最快速度推進我們的產品組合，讓盡可能多的病患能夠使用並受益；我們認為長期而言，這對病患最好，也對 Vertex 最好。

Great. Thank you.

很好。謝謝你。

Thank you. Our next question comes from Howard Liang of Leerink Swann. Your line is open.

謝謝。下一個問題來自 Leerink Swann 的 Howard Liang。請發問。

Thank you very much. I have a couple of questions on VX135. One specific question, on the 40 to 60 patients by the end of the year, just in terms of makeup of that, would that be 20 patients each from each of the ribavirin combination studies and 20 from the Daclatasvir study?

非常感謝。我有幾個關於 VX135 的問題。一個具體問題：關於年底前 40 到 60 名病患，就其組成而言，是否會是每個利巴韋林（ribavirin）聯合研究各 20 名病患，再加上 Daclatasvir 研究 20 名？

Yes, that's approximately right.

是的，大致上是這樣。

Okay. And I guess a question -- a quick follow-up on it, where is the GSK combo study? Have you seen that?

好的。我想再快速追問一下：GSK 的聯合研究進展到哪裡了？你們有看到（資料）嗎？

So, our strategy obviously is to have a number of collaborations and we're moving forward with that. We've started a number of studies so far this year. And we have had the opportunity to start the Daclatasvir study more rapidly, based on BMS. However, we're now evaluating the initiation of the remaining studies, and we will be getting back to you with the time line of that as they go forward.

所以，我們的策略顯然是建立多項合作並持續推進。今年到目前為止我們已啟動了多項研究。而基於 BMS 的因素，我們得以更快速地啟動 Daclatasvir 的研究。不過，我們目前正在評估其餘研究的啟動時點，並會在後續推進時回覆你相關的時間表。

Okay, great. And a broader question is, when you make a decision next year about how to move forward -- what regimen to move forward into phase III, what profile of the combination are you shooting for, is pan-genotypic coverage, specifically genotype 3 coverage, important?

好的，很好。再一個更廣泛的問題：當你們明年做出如何往前推進的決策——也就是要把哪個治療方案推進到第三期（phase III）時，你們希望達到的聯合療法特徵是什麼？是否需要泛基因型（pan-genotypic）涵蓋，特別是基因型 3（genotype 3）的涵蓋很重要嗎？

It is a great question. I think we've said all along, Howard, that we believe today, anyway, from what we've learned, that we are going to need a highly efficacious regimen, which for us means SVRs of greater than 80% certainly in genotype 1. We are going to need a short duration of therapy, which we believe is 12 weeks or less, and we are going to need a very highly tolerable therapy.

這是個很好的問題。Howard，我想我們一直以來都說，我們相信至少就目前我們所學到的而言，我們需要一個高療效的治療方案；對我們來說，這代表在基因型 1（genotype 1）中 SVR 必須高於 80%。我們需要較短的療程，我們認為是 12 週或更短；同時我們也需要非常高的耐受性治療。

In addition, there's some other potential differentiating points, and they really have to do with pan-genotypic, as you point out, and they have to do with some of the sicker patient populations. And our strategy is to investigate our regimens, first for the sort of the basics, if you will, and then see if we can develop differentiated regimens around some of those other properties an get them out there quickly.

此外，還有一些可能的差異化要點，正如你所指出的，與泛基因型相關，也與一些病情更嚴重的病患族群相關。我們的策略是先針對我們的治療方案做基本面的驗證（如果你願意這麼說），然後再看看是否能在其他特性上開發出具差異化的治療方案，並盡快推向市場。

Thanks very much.

非常感謝。

Our next question comes from Phil Nadeau of Cowen and Company. Your line is open.

下一個問題來自 Cowen and Company 的 Phil Nadeau。請發問。

Thanks for taking my questions. Just three quick ones. First on a follow-up to Howard's.

謝謝讓我提問。我有三個簡短問題。第一個是延續 Howard 的問題。

We've seen a couple of doublets in HCV in type one already, and they haven't produced SVR rates of greater than 80%. Are you seeing something preclinically that suggests that VX135 doublet could hit those -- that SVR level, or are these largely done to increase the safety database?

我們已經在 HCV 的第一型（type one）看到幾個雙藥組合（doublets），但它們的 SVR 比例都沒有超過 80%。你們在臨床前是否看到一些跡象顯示 VX135 的雙藥組合可以達到那個 SVR 水準？還是這些研究主要是為了擴增安全性資料庫？

And second, for Ian, could you just let us know what you assume in your guidance is the timing for the launch of Sofosbuvir? Does your guidance anticipate competition from Sofosbuvir in the fourth quarter of this year?

第二個問題給 Ian：你能否說明一下，你們在指引（guidance）中假設 Sofosbuvir 上市的時間點是什麼？你們的指引是否預期今年第四季會面臨 Sofosbuvir 的競爭？

And then third, Jeff, for you, you mentioned moving the second generation correctors along as quickly as possible. Could you give us some updated idea when those could get into the clinic? Thank you.

第三個問題給 Jeff：你提到要盡快推進第二代校正劑（correctors）。你能否更新一下，這些藥物大概何時可能進入臨床？謝謝。

There are a lot of questions. You might have to remind me of a couple of them as we go, but first let me answer the first one. First, I want to be clear, when you are talking about doublets, you're talking about a nuke plus ribavirin, is that right?

問題很多。我們進行時你可能得提醒我其中幾個，但我先回答第一個。首先我想確認一下，你說的雙藥組合，是指核苷（nuke）加上利巴韋林（ribavirin），對嗎？

Yes, that's right.

是的，沒錯。

Yes, we think that -- the reason that we are really pursuing for a nucleus ribavirin first is to understand the safety profile and the potency of our nuke alone before we combine it with other DAAs. But our belief is for the majority of the patients one will need two DAAs and certainly, you can see that reflected in our strategies. I think that is probably the answer to your first question.

是的，我們認為——我們之所以先推進核苷加利巴韋林，主要是為了在與其他 DAA 聯合之前，先了解我們的核苷單藥的安全性特徵與效力。但我們的看法是，對大多數病患而言，需要兩種 DAA；而且你也可以從我們的策略中清楚看到這一點。我想這大概就是你第一個問題的答案。

You want to just repeat the rest of the other three questions so I can remember?

你能把其餘三個問題再重複一次嗎？這樣我才記得。

Yes, so the second one was for you also, and that is an update on when the second generation correctors could get into the clinic. And then the third was for Ian, and that is, what is -- what timing of Sofosbuvir approval is assumed in the guidance that you read today?

可以，第二個也是問你：第二代校正劑大概何時能進入臨床的最新進度。第三個是問 Ian：你今天宣讀的指引中，假設 Sofosbuvir 核准的時間點是什麼？

With respect to the second generation correctors, what we said is our goal is to get one of them or more than one of them into the clinic by the end of next year, that's 2014.

關於第二代校正劑，我們說過，我們的目標是在明年底前，也就是 2014 年底前，讓其中一個或多個進入臨床。

Okay, great, thanks.

好的，很好，謝謝。

And Phil, to the guidance, I will say again, we provided total revenue guidance. The only line item guidance we provided in revenues was to Kalydeco. We have accounted for what we see as the potential decline for patients initiating treatment. I actually mentioned that in my prepared remarks.

Phil，至於指引，我再說一次：我們提供的是總營收指引。我們在營收方面唯一提供的分項指引是 Kalydeco。我們已將我們所看到的、病患開始治療人數可能下滑的情況納入考量。我其實在事先準備的發言中有提到這點。

Okay, great. Thank you.

好的，很好。謝謝。

Our next question comes from Katherine Xu of William Blair. Your line is open.

下一個問題來自 William Blair 的 Katherine Xu。請發問。

Hi, can you hear me?

嗨，你聽得到我嗎？

Yes, hi, Katherine.

是的，嗨，Katherine。

Good evening. I have a couple of questions.

晚安。我有幾個問題。

So when you start the VX135 and the second half of your combo study, are you still going to be required to monitor the cardiac EKG, CG and other markers? Just curious about that.

所以當你們開始 VX135 以及你們聯合試驗的後半段時，你們是否仍然會被要求監測心臟 EKG、CG 以及其他指標？只是好奇這點。

And then are there -- is there a cap of sales in the UK, including Ireland, Scotland and Wales, et cetera, for orphan drugs? Is there a cap on the cumulative sales? Just those two for now.

另外，英國（包含愛爾蘭、蘇格蘭、威爾斯等）對於孤兒藥的銷售是否有上限？累計銷售額是否有上限？目前就這兩個問題。

Bob will take the first question and Stuart will follow-up, Katherine.

Katherine，第一個問題由 Bob 回答，接著 Stuart 補充。

Ultimately the answer is, that is something we will be discussing with the regulatory agencies once we have the initial data going forward. Our hope is that we will have made a substantial clearance of safety with those initial groups of patients. But obviously, the outcome will depend on our discussions with the regulators, so it is kind of hard to really answer that one definitively at this point.

最終的答案是：一旦我們取得初步數據並往前推進，這將是我們會與監管機構討論的事項。我們希望在這些初始病患組別中，已能在安全性方面取得相當程度的釐清。但顯然結果將取決於我們與監管單位的討論，因此目前很難對此給出明確的答案。

And on the -- is there a financial cap for orphan drugs in the UK? There isn't a financial cap in those countries. The real cap is the number of eligible patients with G551D that we can bring benefit to.

至於——英國的孤兒藥是否有財務上限？在那些國家並沒有財務上限。真正的上限是符合資格、帶有 G551D 的病患人數，也就是我們能讓其受益的病患數量。

The only country that kind of has a cap really is Scotland, in that Kalydeco is covered in Scotland under a Red Zs fund. That Red Zs fund was put in place earlier this year, there's about, I think 21 million pounds in that Red Zs fund. That is certainly more than enough to cover Kalydeco for all of the eligible patients in Scotland.

唯一某種程度上真的有上限的國家是蘇格蘭，因為 Kalydeco 在蘇格蘭是透過 Red Zs 基金給付。該 Red Zs 基金於今年稍早設立，基金規模約為（我想）2,100 萬英鎊。這筆金額當然足以涵蓋蘇格蘭所有符合資格病患的 Kalydeco 用藥。

So, I think the short answer to your question, Katherine, is no.

所以，我想對你的問題最簡短的回答是：不，Katherine。

If I may, just a quick follow-up on pricing, when you look at our models for the combo, the double combos for homozygous and potentially the triple combo for heterozygous, how do we -- how should we think about pricing? Do we look at the similar pricing of Kalydeco right now? Or should we think --?

如果可以的話，我想就定價再追問一下：當你看我們對聯合療法的模型——同型合子可能是雙聯合，異型合子可能是三聯合——我們該如何思考定價？是參考目前 Kalydeco 類似的定價嗎？還是我們應該——？

Well, I'm not going to tell you how you should look at pricing, but what I will say is this is far too early for us to be talking about pricing when we've really only just begun the phase II program for 809. And it is really much too early in the process to be making any comments on price from our end.

嗯，我不會告訴你應該如何看待定價，但我可以說的是：現在談定價還太早，因為我們其實才剛開始 809 的第二期計畫。在流程的這麼早期階段，我們這邊也確實還不適合對價格做任何評論。

Thanks.

謝謝。

Operator, this is Michael Partridge. Given the time, we will take one more question.

接線員，我是 Michael Partridge。考量時間，我們再接受最後一個問題。

Our final question comes from Salveen Richer of Canaccord Genuity. Your line is open.

我們最後一個問題來自 Canaccord Genuity 的 Salveen Richer。你的線路已開通。

On the 661 program, I think have you additional studies reading out in the second half. Can you maybe comment on what these studies are and whether we should expect 983 data in the second half as well?

關於 661 計畫，我想你們在下半年還會有其他研究讀出結果。你能否評論一下這些研究是什麼，以及我們是否也應該預期下半年會有 983 的數據？

And then on Kalydeco, and I could be wrong here, but I think you took a price increase in January, but you're looking at the last three quarters being flat. So, just wondering what was playing out in Q1? Were there dropouts or so forth? Thanks.

另外關於 Kalydeco，我可能記錯，但我記得你們在一月調漲了價格，但你們看到最近三個季度是持平的。所以想請問第一季發生了什麼？是否有停藥或類似情況？謝謝。

Maybe I will take the disclosure of data in the second half of the year. We don't anticipate any significant data disclosures regarding VX261 in the second half of the year. Although we did mention on our call the other week that we do need to take the data we received from the current -- the most recent phase II study and other studies and have a discussion with the regulatory authorities. That will then put is in a position to communicate to you the next steps of VX661.

也許我先回答下半年數據揭露的部分。我們不預期下半年會有任何關於 VX261 的重大數據揭露。不過我們在前幾週的電話會議中確實提到，我們需要把目前——最近一次第二期研究以及其他研究所取得的數據，拿去與監管機關討論。之後我們才會處於能向各位溝通 VX661 下一步的狀態。

If I try and think about other data regarding CF in the second half of the year, it would probably be at the medical conference and specifically, the US-based medical conference for cystic fibrosis. And as I said earlier on the call, we don't pre-announce what we will be disclosing at that meeting. And your second question, I'm sorry?

如果我試著想下半年還有哪些與囊性纖維化（CF）相關的其他數據，可能會是在醫學會議上，特別是美國的囊性纖維化醫學會議。如同我先前在電話會議中所說，我們不會預先公告在那場會議上將揭露哪些內容。至於你的第二個問題，不好意思是什麼？

It was on price, Ian. I think -- let me take that one. We did take a price increase in the US within the quarter. That's correct.

是關於價格，Ian。我想——讓我來回答這題。我們確實在本季度於美國進行了價格調漲。這是正確的。

From quarter to quarter, there is really multiple factors that can affect our revenue. There's lots of puts and takes, as it were, within one particular quarter.

從一季到下一季，確實有多種因素會影響我們的營收。如同常說的，在單一季度內會有很多正負因素相互拉扯。

Let me just address one thing that I think you are alluding to, was there was a dropoff or increased dropoff of patients? That didn't happen. Our persistence and compliance rates are very high with Kalydeco and have been very stable over time.

我先回應一點，我想你在暗示的是：病患是否有流失或流失增加？並沒有發生這種情況。Kalydeco 的持續用藥率與依從性非常高，而且長期以來都非常穩定。

What we're really focused on is the annual revenues for Kalydeco. We feel very good about the revised guidance that we provided today.

我們真正關注的是 Kalydeco 的年度營收。我們對今天提供的修正後指引感到非常有信心。

And Salveen, I was just checking my notes, you mentioned what we would be doing for VX983 in the second half of the year. And just a couple of weeks ago when we had our call, we also talked about entering a combination study in patients with VX983 in either cap, so that would be in the second half as well. Whether we receive data from that, unsure at this point in time. That study has not started yet.

另外 Salveen，我剛在看我的筆記，你提到下半年我們對 VX983 會做什麼。就在幾週前的電話會議上，我們也談到會在下半年啟動一項在病患中進行的 VX983 聯合試驗（不論是哪一個組別）。至於是否能從中取得數據，目前還不確定。那項研究尚未開始。

So Salveen, thanks very much for that. And on behalf of the Vertex team, thanks very much for joining us tonight. If you have additional questions, we will be in the office and we will be happy to take your call. Thank you.

所以 Salveen，非常感謝你的提問。我也代表 Vertex 團隊，感謝各位今晚加入我們。如果你們還有其他問題，我們會在辦公室，也很樂意接聽你們的來電。謝謝。

Thank you. Ladies and gentlemen, this concludes the conference for today. You may all disconnect and have a wonderful day.

謝謝。各位女士先生，今天的電話會議到此結束。各位可以掛線，祝各位有美好的一天。