Assembly Biosciences Inc (ASMB) 2011 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Ventrus Biosciences' third-quarter 2012 results and clinical update conference call. At this time, all participants' lines are in the listen-only mode. Later, we'll conduct a question-and-answer session, and instructions will be given at that time. (Operator Instructions). As a reminder, this conference is being recorded.

女士們，先生們，大家好！歡迎參加Ventrus Biosciences 2012年第三季業績及臨床更新電話會議。目前，所有與會者的線路均處於只聽模式。稍後我們將進行問答環節，屆時將提供操作說明。 （操作員指示）。提醒一下，本次會議正在錄音中。

The presenters for today's conference call is Dr. Russell Ellison, Chief Executive Officer of Ventrus Biosciences, and David Barrett, Chief Financial Officer of Ventrus Biosciences. I would now like to turn the conference over to Dr. Ellison. Please go ahead, sir.

今天的電話會議主持人是 Ventrus Biosciences 執行長 Russell Ellison 博士和財務長 David Barrett。現在，我想將電話會議交給 Ellison 博士。先生，請開始。

Thank you. Hello, everyone. Thank you very much for joining us this morning. I do apologize for the early hour. We have actually a fair amount of news to get through here, so I'm going to try to be as concise as possible.

謝謝大家。大家好。非常感謝大家今天早上加入我們。很抱歉這麼早就來了。我們其實有很多新聞要發布，所以我會盡量簡潔地講。

First, though, please, do refer to the forward-looking statements we have in the slide deck. These were updated, consistent with the material we're talking about today. So, if you go to slide two, I'm going to just give a summary of the update we're going to give. And then David will start with the financials, and then I'll take over for the other agenda items.

不過，首先，請務必參閱投影片中的前瞻性陳述。這些陳述已更新，與我們今天討論的內容一致。請翻到第二張投影片，我將簡要介紹我們將要發布的更新內容。然後，David 將先介紹財務狀況，之後我將負責其他議程。

So, first of all, at the end of quarter 3, 2011, we had $53 million in cash on our balance sheet and no debt. With respect to the programs, I'm happy to say that we're on track to deliver Phase 3 data on our two significant lead compounds, GI drugs, for anal fissures and hemorrhoids by the middle of 2012. For VEN 309, topical iferanserin, the 5-HT2A antagonist for the treatment of hemorrhoids, the top-line data from the pivotal trial, and in addition, clinical pharmacology data, are now expected around June 2012. This is a change from our previous guidance and I'll go over this in some detail.

首先，截至2011年第三季末，我們的資產負債表上有5,300萬美元現金，沒有債務。關於項目，我很高興地說，我們正按計劃在2012年中期發布兩種重要的先導化合物（胃腸道藥物）的三期臨床試驗數據，用於治療肛裂和痔瘡。對於用於治療痔瘡的5-HT2A拮抗劑VEN 309（外用伊弗蘭色林），其關鍵性試驗的最終數據以及臨床藥理學數據預計將於2012年6月左右發布。這與我們先前的預期有所不同，我將對此進行詳細介紹。

However, it's very important to note the NDA filing timelines for this product remain unchanged, inasmuch as these trials are not on critical path. In addition, the data quality is good. Good clinical research practice procedures are good. And I'm happy to say that no serious severe adverse events related to the drug have been seen to date.

然而，需要特別指出的是，由於這些試驗並非處於關鍵階段，因此該產品的新藥申請 (NDA) 提交時間表保持不變。此外，數據品質良好。良好的臨床研究實踐 (GRP) 程序也很好。我很高興地說，迄今尚未發現與該藥物相關的嚴重不良事件。

With respect to the anal fissure product, topical diltiazem, VEN 307 for the treatment of anal fissures, top-line data is still expected in the second quarter of 2012, probably around May. This means that both studies are likely to report out very close to each other, and anal fissure may be first.

關於治療肛裂的外用地爾硫卓（VEN 307）產品，預計仍將於2012年第二季（可能在5月左右）公佈頂線數據。這意味著兩項研究的報告時間可能非常接近，而肛裂治療的研究結果可能是第一項。

In addition, I'm going to be talking about the market research that we've just conducted, the consumer part of it, where we surveyed 10,000 consumers to look at 1,100 hemorrhoid patients. And that does confirm that hemorrhoid prevalence is indeed, high, and in fact, it exceeds our previous estimates, and that patients are taking action. In addition -- and this is the first time we've been able to look at this -- we did expose people to -- the hemorrhoid to the product concept, and their response is strong.

此外，我還要談談我們剛剛進行的市場調查，其中涉及消費者的部分。我們調查了1萬名消費者，並分析了1,100名痔瘡患者。這確實證實了痔瘡的盛行率確實很高，甚至超過了我們先前的估計，而患者正在採取行動。此外——這是我們第一次進行這方面的研究——我們確實向人們介紹了——痔瘡產品的概念，他們的反應非常強烈。

Finally, we're delighted to be able to close the transaction to acquire the rights and title for VEN 309, our hemorrhoid product today.

最後，我們很高興能夠完成交易，並獲得我們的痔瘡產品 VEN 309 的權利和所有權。

So, I'm going to turn this over to David briefly to go over our financial update, and then I'll come back and take us through the clinical programs and the market research. David?

那麼，我將把這個交給大衛，讓他簡要介紹一下我們的財務更新情況，然後我會回來帶我們了解臨床項目和市場研究。大衛？

Thank you. Ventrus reported a net loss of approximately $15.5 million, $1.79 per share for the nine months ended September 30, 2011. Net cash used in operating activities was approximately $8.7 million for the nine months. The primary reason for the difference are attributed to stock-based compensation charges.

謝謝。 Ventrus 報告稱，截至 2011 年 9 月 30 日的九個月，淨虧損約為 1,550 萬美元，每股虧損 1.79 美元。九個月內，經營活動所用淨現金約 870 萬美元。造成這種差異的主要原因是股票薪酬費用。

Research and development expenses for the third quarter of 2011 increased to $3.7 million from $193,000 in the same period last year. General and administrative expenses for the third quarter of 2011 increased to $1.6 million from $317,000 in the same period last year.

2011年第三季研發費用從去年同期的19.3萬美元增加至370萬美元。 2011年第三季一般及行政費用從去年同期的31.7萬美元增至160萬美元。

Our financial performance in the third quarter reflects our strategy of moving our product development programs forward. Based on our current operations, we currently expect our cash burn for the next 12 months to be between $12 million and $16 million, excluding the Amer acquisition. We believe that our existing cash and cash equivalents at September 30, 2011 will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into 2014.

我們第三季的財務表現反映了我們推進產品開發專案的策略。根據目前的營運情況，我們預計未來12個月的現金消耗將在1,200萬美元至1,600萬美元之間（不包括收購Amer的費用）。我們相信，截至2011年9月30日的現有現金及現金等價物足以滿足我們2014年的營運支出和資本支出需求。

Dr. Ellison?

艾里森博士？

Thank you, David. So I'm going to now give you some more color on the clinical programs. So let's start with the hemorrhoid product, VEN 309 -- 0.5% ointment applied twice daily, intra-anally.

謝謝你，大衛。現在我要給你詳細介紹一下臨床方案。我們先從痔瘡產品VEN 309開始－0.5%的藥膏，每天兩次，肛內塗抹。

The ongoing pivotal trial that we initiated in August this year has three arms, with 200 patients per arm. You get either a 14-days treatment of drug or 7-days treatment of drug followed by placebo for a week; or 2 weeks of placebo, followed by 2-week observations for the double-blind part. That makes a total of 600 patients that we're doing in 70 sites.

我們在今年8月啟動的正在進行的關鍵性試驗分為三個組，每組200名患者。患者可以選擇接受14天的藥物治療，或接受7天的藥物治療後服用一週的安慰劑；或接受2週的安慰劑治療，然後進行2週的雙盲觀察。這樣一來，我們在70個研究中心總共招募了600名患者。

After the double-blind part, there is a one-year open label extension so we can observe the recurrence rate and treat for recurrence. This is very important for designing the rest of the program. And very importantly, the primary endpoint is cessation of bleeding from day 7 to day 14. That is to say, you have to stop bleeding by day 7 and have no further bleeding through day 14.

雙盲研究結束後，還有一年的開放標籤延長期，以便我們觀察復發率並進行治療。這對於設計後續方案至關重要。而且非常重要的是，主要終點是第7天至第14天止血。也就是說，你必須在第7天止血，並且到第14天不再出血。

The secondary endpoints are pain and itching, evaluated the same way. And we collect these endpoints using an interactive voice response system on a daily basis.

次要終點是疼痛和搔癢，評估方式相同。我們每天使用互動式語音應答系統收集這些終點數據。

Now, in order to get the meaning -- have the meaningful improvement, patients have to enter the trial with meaningful symptoms. So they need to have 2 consecutive days of bleeding plus itching or pain. And the other thing you have to not have to get into the trial is, you can't have a history or existing depression and you can't be on any SSRIs. And you can have a history of heart disease, extreme BMI or some other chronic diseases. And the reason for those are, is that we don't have our drug/drug interaction studies yet. And so we have to exclude depression and all SSRIs until we know which ones are actually going to be relevant.

現在，為了獲得有意義的改善，患者必須帶著有意義的症狀參加試驗。也就是說，他們需要連續兩天出現出血，並伴隨搔癢或疼痛。此外，參與試驗也必須符合以下條件：患者不能有憂鬱症病史或正在服用憂鬱症藥物，也不能服用任何選擇性5-羥色胺再攝取抑制劑 (SSRI)。此外，患者不能有心臟病史、極端體重指數或其他慢性疾病史。原因是我們還沒有進行藥物交互作用研究。因此，在確定哪些藥物與試驗結果相關之前，我們必須排除憂鬱症和所有選擇性5-羥色胺再攝取抑制劑。

And for the other diseases, because we have a one-year open label extension study without a placebo, we didn't want to have people who could have lots of events of -- through that year, which would be very difficult to interpret. And in addition, because we have the one-year extension, we needed to have people have a colonoscopy prior to entry if they hadn't had one in less than three years ago, because we really have to be sure that -- rule out any other cause of the bleeding, namely cancer or polyps, that kind of thing, because we're going to be following them open label for a year.

對於其他疾病，由於我們進行了為期一年的開放標籤延伸研究，沒有使用安慰劑，我們不希望受試者在研究期間出現大量出血事件，因為這些事件的解釋會非常困難。此外，由於我們進行了為期一年的延伸研究，如果受試者在三年內沒有做過大腸鏡檢查，我們需要在入組前進行大腸鏡檢查，因為我們必須確保排除任何其他出血原因，例如癌症或息肉之類的，因為我們將對他們進行為期一年的開放標籤追蹤。

The progress of the study as that we initiated in early August with 65 sites. And very soon after, we had all 70 sites active. We are, in fact, enrolling the correct patients according to the criteria. And we have a minimal loss of key outcome data, which is very important in symptomatic studies. And we're able to review the data real-time, every day.

這項研究的進展與我們8月初啟動時一樣，當時有65個研究中心參與。很快，所有70個研究中心都開始運作。事實上，我們正​​在根據標準招募正確的患者。我們幾乎沒有失去關鍵結果數據，這在對症研究中非常重要。而且我們能夠每天即時審查數據。

As we expected, we have a very large number of patients wanting to get into the trial and answering screening. Now, our estimated timelines -- the previous guidance was that we said we would complete enrollment in the early part of 2012, January and February, and then we'd therefore be able to have the double-blind data and the recurrence data we have to date in the first quarter of 2012.

正如我們預期的那樣，有大量患者希望參與試驗並接受篩選。目前，我們預期的時間表是－先前的指導是，我們將在2012年初（1月和2月）完成患者招募，這樣我們就能在2012年第一季獲得雙盲數據和迄今為止的復發數據。

However, we're going to update this guidance based on the three months of solid enrollment that we've now had which has been fairly constant. And looking forward, we've adjusted that downwards for a slowdown in the Thanksgiving to New Year period. And so we now see enrollment being complete in April 2012, with the double-blind data and open label recurrence data being available around June 2012.

然而，我們將根據目前三個月以來的穩定招募情況更新此指導方針。展望未來，我們已下調了這項預期，以應對感恩節到新年期間的放緩。因此，我們現在預計招募工作將於2012年4月完成，雙盲資料和開放標籤復發資料將於2012年6月左右公佈。

This change in guidance is due to a screen failure rate that was higher than expected. This was partially due to the need for having symptoms 2 days consecutively. Nobody really knew about hemorrhoid patients about how they have their symptoms. And we're finding out that 2 consecutive days, actually people have to have pretty meaningful disease, which is actually what we want. And the other part is that these exclusion criteria that we've put in exceptionally for this study have knocked out a fair number of patients.

此次指南變更是由於篩檢失敗率高於預期。部分原因是需要連續兩天出現症狀。先前沒有人真正了解痔瘡患者的症狀是如何出現的。我們發現，連續兩天出現症狀其實需要患者病情相當嚴重，這正是我們想要的。另一方面，我們為這項研究特別設定的排除標準，已經排除了相當多的患者。

The interesting thing is the impact on future studies should be less, because since we'll have drug/drug interaction studies by the time we start that, and because neither trial will have an open label extension, we'll be able to do colonoscopy after people have received an acute treatment. And we'll be able to have very specific criteria for SSRIs. We'll be able to include people with depression, heart disease, and other chronic illnesses.

有趣的是，這對未來研究的影響應該較小，因為到那時我們就會進行藥物交互作用研究，而且這兩項試驗都沒有開放標籤擴展，所以我們可以在患者接受急性治療後進行大腸鏡檢查。而且，我們將能夠制定非常具體的SSRIs標準。我們將能夠納入憂鬱症、心臟病和其他慢性疾病患者。

Now that, as I said, this new timeline has no affect on our NDA filing timelines and no material effect on our balance sheet. We will be reporting out around the same time our clinical pharmacology program, which is related to the metabolism of the drug by the enzyme CYP2B6, which is in the liver. This product is entirely dependent on CYP2B6 for its metabolism and also inhibits it. This is kind of an advantage if you have a GI topical drug, because you get a big first pass effect. So you get low systemic exposure. But we also have to look at extreme exposures for this to derisk the safety profile.

正如我所說，新的時間表不會影響我們的新藥申請 (NDA) 提交時間表，也不會對我們的資產負債表產生實質影響。我們將在大約同一時間發布臨床藥理學計畫報告，該計畫與藥物通過肝臟中的 CYP2B6 酶代謝有關。該產品完全依賴 CYP2B6 進行代謝，同時也會抑制它。對於胃腸道外用藥物來說，這算是優勢，因為首過效應顯著，因此全身暴露量較低。但我們也必須考慮極端暴露量，以降低安全性風險。

So this study is going to look at people who metabolize the drug poorly. That is to say, they have deficient CYP2B6 metabolism. And we're also going to look at drug/drug interactions with Cymbalta as an example of a moderate inhibitor for SSRIs, and also Dextromethorphan, which actually is the model for the other drug.

因此，這項研究將關注那些藥物代謝不良的人。也就是說，他們的CYP2B6代謝缺陷。我們也將研究藥物交互作用，以欣百達為例，欣百達是SSRI類藥物的中度抑制劑，右美沙芬其實是另一種藥物的模型。

This is important to be doing this in parallel with the pivotal trial, because when this report is out, we expect to have less restrictions in the inclusion criteria for the next studies. And this, as I said, helps to derisk the safety profile and also provides us the high dose arm for our thorough QT study, which we'll be doing following getting these data and are needed for the NDA.

與關鍵試驗同時進行非常重要，因為這份報告發布後，我們預期後續研究的納入標準會減少限制。正如我所說，這有助於降低安全性風險，也為我們全面的QT研究提供了高劑量組。我們將在獲得這些數據後進行這項研究，這也是NDA申請所必需的。

We're looking forward to seeing these data because we already did have one poor metabolizer who actually couldn't metabolize the drug at all in our Phase 1 study. And exposed to the single dose, he had no adverse events.

我們期待看到這些數據，因為在我們的第一期研究中，確實有一位代謝較差的患者，他實際上根本無法代謝這種藥物。而他接受單一劑量治療後，並沒有出現任何不良反應。

So with respect to anal fissure, VEN 307, just to recall, this is a 3-arm study being done in 155 patients per arm in 31 sites in Europe. It's got a 3-month double-blind period, two-months' treatment and one-month's follow-up. And the primary endpoint is reduction in pain on defecation at one month; secondary at two months. And we're using a validated Likert Scale for this.

關於肛裂，VEN 307，簡單回顧一下，這是一項三組研究，在歐洲31個研究中心進行，每組155名患者。研究包括3個月的雙盲期、兩個月的治療和一個月的追蹤。主要終點是1個月時排便疼痛減輕；次要終點是2個月時排便疼痛減輕。我們使用經過驗證的李克特量表來評估療效。

And we've recently been over to visit our partner and get a detailed review of the blinded data and study operations in October. And we're very encouraged by this. We have the right patients enrolled; we have good clinical research practices; the IVRS compliance of looking at the symptoms is good to date. And they, like us, are reviewing the data continuously on a daily basis.

我們最近拜訪了我們的合作夥伴，並在十月詳細審查了盲法數據和研究操作。我們對此感到非常鼓舞。我們招募了合適的患者；我們擁有良好的臨床研究實踐；迄今為止，IVRS 症狀監測的依從性良好。而且他們和我們一樣，每天都在持續審查數據。

We do expect with this trial, as planned, to have enrollment complete by January 2012. And that means we should be able to expect the unblinded data to be available around May 2012. As I said, this means the two trials are going to report out fairly close together, and anal fissure may be first.

我們確實希望這項試驗能夠按照計劃在 2012 年 1 月完成患者招募。這意味著我們應該能夠預期在 2012 年 5 月左右可以獲得揭盲數據。正如我所說，這意味著兩項試驗的報告將會相當接近，而肛裂可能是第一個。

Now let me move on to the market research we just did. This is a landmark study. This is what's called an omnibus study in marketing terms, which is the kind of thing you do for big drugs every five years. But we wanted to really get a much better fact-based to understand the commercial potential for this study, because there was very little data out there previously.

現在，我來談談我們剛剛做的市場研究。這是一項具有里程碑意義的研究。用行銷術語來說，這稱為綜合性研究，也就是每五年針對大型藥品進行一次的研究。但我們希望獲得更充分的基於事實的證據，以了解這項研究的商業潛力，因為先前的數據非常少。

So we commissioned this study, which is primarily developed a good forecast. In September from Princeton Brand Econometrics, who we chose because of their rigor, and they have an amazing track record with 9 of the top 10 pharmaceutical companies and 31 in-market validated forecasts, which have a very low margin of error. The Physician Project, where we're surveying 800 physicians, has completed but it is just starting the analysis stage, so we don't have tables yet. But the consumer project is farther along and we do have data tables. I'm going to be discussing some of those with you today.

因此，我們委託普林斯頓品牌計量經濟學公司進行了這項研究，主要目的是製定一個準確的預測。我們選擇普林斯頓品牌計量經濟學公司是因為他們嚴謹的研究態度，他們擁有出色的業績記錄，曾與全球十大製藥公司中的九家合作，並進行了31次市場驗證預測，誤差幅度非常低。我們正在調查800名醫生的「醫生專案」已經完成，但才剛進入分析階段，所以我們還沒有表格。但消費者專案進展較快，我們確實有數據表格。今天我將與大家討論其中的一些內容。

It's important to understand our study approach. First of all, when we expose someone to a product concept, you only get exposed to one concept -- not multiple ones. And this is very important with respect to the predictability of the data. And Princeton Brand Econometrics actually factors or discounts responses to product concepts and what people say they're going to do, based on other questions in the questionnaire -- if you will, worked out with their previous experience with their other forecasts, so they can get a pretty good predictive model on this. And this is what we call PBE factoring.

理解我們的研究方法至關重要。首先，當我們向人們展示一個產品概念時，你只會接觸到一個概念，而不是多個。這對於數據的可預測性至關重要。普林斯頓品牌計量經濟學實際上會根據問卷中的其他問題（如果你願意的話，可以結合他們之前在其他預測方面的經驗）來對產品概念的回答以及人們的預期行為進行因子分解或折算，這樣他們就能得到一個相當不錯的預測模型。這就是我們所說的PBE因子分解。

So if we look at the results with respect to how many patients there are, as I said, we screened 10,202 adult consumers, which the sample frame is designed to match US demographics. And that revealed that 1,125 of these consumers reported suffering from hemorrhoids within the last two years. That's 11%. And given that the US adult population in 2010 is about 234 million, that means that people having had hemorrhoids in the last two years is about 25.8 million.

所以，如果我們從患者數量來看結果，正如我所說，我們篩選了10,202名成年消費者，樣本框架的設計與美國人口統計數據相符。結果顯示，其中1,125名消費者報告在過去兩年內患有痔瘡，佔11%。考慮到2010年美國成年人口約為2.34億，這意味著過去兩年內患痔瘡的人數約為2580萬人。

If you extrapolate the people who said they had hemorrhoids in the last year, that's 9.3% or 21.7 million, which is the normal prevalence, and that compares to the 12.5 million we had before. And the one-month prevalence at 6%, that is to say, people who suffered from hemorrhoids in the last month, that would mean 14 million people. And very interestingly, people who are suffering hemorrhoids on the day of the survey, that is to say, for example, today, was 2.9% at 6.7 million people.

如果將過去一年中自稱患有痔瘡的人數推算出來，那麼患病率就是9.3%，也就是2170萬人，這是正常的患病率，而之前的患病人數是1250萬人。如果將一個月的盛行率計算為6%，也就是說，過去一個月曾患過痔瘡的人數，就代表有1,400萬人。有趣的是，調查當天，也就是今天，患痔瘡的人數為2.9%，即670萬人。

Now the people that were treated, 15% never used over-the-counter or RX treatment, but of those, 85% did one or the other. And of those who are taking treatment, 86% reported having used an OTC in their last treatment and 14% reported using a prescription drug on their last treatment. Of the whole sample, 10% reported having had an invasive procedure -- 61% of these were surgery, and the others were banding and injections. And interestingly, 75% of the people who have had an invasive procedure reported a recurrence, which is a number I hadn't actually seen before.

在接受治療的患者中，15% 從未使用過非處方藥或處方藥治療，但其中 85% 的患者使用了其中一種或兩種藥物。在接受治療的患者中，86% 的患者報告在上次治療中使用了非處方藥，14% 的患者報告在上次治療中使用了處方藥。在整個樣本中，10% 的患者報告接受侵入性手術——其中 61% 是手術，其餘是套紮和注射。有趣的是，75% 接受過侵入性手術的患者報告復發，這是我以前從未見過的數字。

Now with respect to the response to the iferanserin product concept, it turns out that there is a very strong willingness for patients to ask their doctor for this product at their next visit, if, in fact, they were exposed to a standard DTC PR campaign. So in the entire sample, which includes people who are satisfied with their previous treatment; people who weren't; people who had different -- all different severities of hemorrhoids; and people who had all different levels of income -- when exposed to the product concept, 75% stated that they would request a prescription at their next visit. And if you factor this by the other questions in the questionnaire and PBE's methodology, you get 25% probably actually would request a prescription.

現在，關於對伊弗蘭色林產品概念的反響，事實證明，如果患者接觸到標準的DTC公關活動，他們非常願意在下次就診時向醫生索要該產品。因此，在整個樣本中，包括對先前治療滿意的人、不滿意的人、不同程度痔瘡的人以及不同收入水平的人，在接觸到該產品概念後，75%的人表示他們會在下次就診時索要處方。如果將這一因素與問卷中的其他問題以及PBE的方法結合起來，你會發現25%的人可能真的會要求處方。

Now of those who actually got a prescription, 66% said they would fill that prescription at a $35 out-of-pocket patient co-pay. That's actually also factored by PBE, and it includes the usual loss that you get irrespective of price, when people get a prescription and don't fill it.

在那些真正拿到處方的人中，66%的人表示，他們願意以35美元的自付費用（病人自付額）來配藥。這實際上也包含在PBE中，它包含了人們拿到處方卻不配藥時通常產生的損失，無論價格如何。

Now people with a household income above $50,000 a year, which is the median US household income, 78% of those people said they would fill the prescription at a $35 out-of-pocket patient co-pay. Interestingly, for people who are having symptoms today -- that's the estimate of 6.7 million -- 88% stated they would request a prescription if they saw this product concept. And if you factor this, 80% would actually request it.

現在，家庭年收入超過5萬美元（美國家庭收入中位數）的人群中，78%的人表示，他們願意以35美元的自付費用（病人自付）來配藥。有趣的是，對於目前出現症狀的患者（估計有670萬人），88%的人表示，如果他們看到這個產品概念，他們會要求開處方。如果考慮到這一點，80%的人會真正提出要求。

Now given that, we're very happy to be able to close the acquisition of the rights and title of VEN 309, which we anticipate being done today. This is where we're purchasing the global rights and title to all aspects of the product. We're going to be decreasing US royalties from double digits to 4%, and rest of the world from mid-single digits to 1%. We're going to decrease the milestones by about $10 million. And we did pay $0.5 million on execution of the contract, which we did in 2011. And $12 million will be due on closure, if the transaction closing conditions were met, and indeed, they were.

有鑑於此，我們很高興能夠完成對VEN 309權利和所有權的收購，預計今天即可完成。我們將購買該產品所有方面的全球權利和所有權。我們將把美國的專利費從兩位數降至4%，世界其他地區的專利費從個位數中段降至1%。我們將把里程碑付款減少約1000萬美元。我們在2011年執行合約時支付了50萬美元。如果交易成交條件得到滿足，而且確實如此，那麼在交易完成時，我們將支付1200萬美元。

So one of the conditions was no severe serious adverse event possibly related to the drug, as of November 11 in the ongoing studies -- and in fact, that's the case -- and that we had raised sufficient capital in the follow-on, which we did.

因此，條件之一是，截至 11 月 11 日，在正在進行的研究中沒有發生可能與該藥物相關的嚴重不良事件 - 事實上，情況確實如此 - 並且我們在後續研究中籌集了足夠的資金，我們確實這樣做了。

So that's the end of the presentation and I'll now open this up to questions.

演講到此結束，現在我可以開始回答問題了。

(Operator Instructions). Bill Tanner, Lazard Capital Markets.

（操作員指令）。比爾·坦納（Bill Tanner），拉扎德資本市場（Lazard Capital Markets）。

Thanks for taking the question. Congratulations on the progress. Russ, a few questions, just as it relates to the open label extension period in the 309 trial. Wonder if you could speak a little bit as to the retention -- what are your thoughts on retention of patients in there and how that's going to be achieved? And are there any challenges, I guess, in that? Either in keeping the patients or if more drop out than I guess you might expect, what does that actually do to the analysis?

感謝您的提問。祝賀您取得進展。 Russ，我有幾個問題，關於309試驗的開放標籤延長期。您能否談談患者保留率的問題？您對病患保留率有什麼看法？如何實現？這其中是否存在一些挑戰？是保留患者，還是如果退出率超出預期，這對分析會有什麼影響？

First of all, thanks very much, Bill, and good morning to you. Before I answer this question, I just want to say the slides that I just presented have been filed in an 8-K, so they're available there. And later today, they'll be posted on our website.

首先，非常感謝，比爾，早安。在回答這個問題之前，我想說一下，我剛剛演示的幻燈片已經歸檔到8-K文件中，所以可以在那裡找到。今天晚些時候，它們會發佈到我們的網站上。

So the answer to your question -- so the one-year extension trial has -- extension part of the trial has one advantage that people are going to get active drug. That's always an incentive to people, versus you're going to be there for a year and you may still be getting placebo. So that's an incentive.

所以，你問題的答案是──一年延長試驗──試驗的延長部分有一個好處，那就是人們將獲得活性藥物。這對人們來說總是一種激勵，如果你要進行一年的試驗，你可能仍然只能獲得安慰劑。所以這是一種激勵。

With respect to retention, so far it's too early. I mean, it's been a very short time. But looking forward, we can actually suffer a bit of this. And I'll give you an example. So, if people decide not to come back for re-treatment with the drug -- go to over-the-counter, get a prescription for steroids or something like that -- we do expect them back every quarter. And because we have the IVRS system and we have everybody's phone numbers, and we've already been doing robo calls four times in evening to make sure people dial in, we're able to contact these people and get them to at least come in for the follow-up visit.

關於留存率，目前還言之過早。我的意思是，時間還很短。但展望未來，我們實際上可能會因此受到一些影響。我舉個例子。如果患者決定不再回來接受藥物治療——去非處方藥店，開類固醇處方之類的——我們確實希望他們每個季度都能回來。因為我們有IVRS系統，我們掌握了每個人的電話號碼，而且我們已經在晚上進行了四次自動呼叫，以確保人們撥入，這樣我們就能聯繫到這些人，讓他們至少來複診。

That's important because -- and we're able to track this extremely well. That's actually very important because in these longer-term situations, you really have to keep in touch with people and make sure they want to come back in. So we're anticipating that the sites will also be calling them up in between their quarterly visits, to make sure that these people are still motivated and so on -- particularly if they haven't come in for a re-treatment in between.

這很重要，因為——而且我們能夠非常精準地追蹤這一點。這實際上非常重要，因為在這些長期情況下，你真的必須與患者保持聯繫，確保他們願意回來。因此，我們預計各治療點也會在季度訪問期間給他們打電話，以確保這些人仍然有動力等等——尤其是如果他們在此期間沒有來接受復治的話。

So, just to say that because this is open label and because we want to get an assessment of recurrence, what we'll have is if someone doesn't come back, let's say, for the quarter two visit, is you call up what you always do to make sure they're okay, and they haven't died or had a serious event or something else bad hasn't happened to them. At that point, we ask about if they had a recurrence. So we can keep filling in data quarter-by-quarter, even if we get dropouts.

所以，因為這是開放標籤研究，而且我們想要評估復發情況，所以如果有人在第二季度沒有回來，我們會進行常規檢查，以確保他們一切安好，沒有死亡、沒有發生嚴重事件或其他不好的事情。這時，我們會問他們是否復發。這樣，即使有患者退出研究，我們也可以繼續按季度補充數據。

So that's how we intend to evaluate that. This is really to determine primarily how we're going to design our double-blind recurrence trial that we're going to need to do for the FDA, in terms of how many people we have to treat open label at the beginning in order to get the number of recurrences that we need. And actually, I would suspect that probably by the time the data report out in June, we'll have a pretty good idea of that already.

這就是我們打算評估的方式。這主要是為了確定我們將如何設計我們需要為FDA進行的雙盲復發試驗，即為了達到我們所需的複發數量，我們需要在一開始就進行多少例開放標籤治療。實際上，我估計到6月數據報告發佈時，我們可能已經對此有了相當清晰的了解。

Okay. That's helpful. And then as it relates to your survey, the 14% of patients that are using a prescription treatment, I guess, presumably that would be cortisone steroids. Do you have any -- I understand I guess the data are still being crunched -- do you have any visibility as to that? (multiple speakers)

好的。這很有幫助。然後，關於您的調查，14%的患者正在使用處方藥，我猜，這大概是可的松類固醇。您有什麼資訊嗎？我知道，我猜數據還在處理中。您對此有什麼了解嗎？ （多位發言者）

It is all prescription-strength steroids.

它們都是處方強度的類固醇。

And are there queries of the patients in terms of their satisfaction with those (multiple speakers) [cortisone] --?

病人對這些（多位發言者）[可的松]的滿意度是否有疑問？

Yes, we do have that. And the next crunch is the satisfaction with prior treatment, be it OTC or steroids. And their willingness to ask for a prescription and fill the prescription if they're exposed to the product concept. And that's going to be very interesting data to see if satisfaction with prior treatment does affect that. I would say that the information I've presented includes people who are satisfied with prior treatment.

是的，我們確實有這個數據。接下來的關鍵是患者對先前治療的滿意度，無論是非處方藥或類固醇。以及他們在接觸到產品概念後，是否願意索取處方並配藥。這將是非常有趣的數據，看看既往治療的滿意度是否會影響這一點。我想說，我提供的資訊包括對既往治療感到滿意的患者。

Okay. And then I guess the last question just as it relates to the poor metabolizers, how do you think that would be -- would it be contraindicated in patients that (multiple speakers) --?

好的。那麼我想最後一個問題，就像它與代謝較差的人有關一樣，您認為這會怎麼樣——對於（多位發言者）的患者來說，這是否是禁忌症？ ——

Now, here's how this works. So, first of all, we have one patient in the Phase I who had three times a CMAX and about 9 times [AUC]. So that's on a single dose. If people who are poor metabolizers get side effects -- let's say they get dizzy; flushed, something like that, then it's, in the label, you do what you did with Prozac. If you start having these side effects, you discontinue the drug, because you may be a poor metabolizer. And then they can get their genes done to see if they can continue to take the product.

現在，我們來看看它的工作原理。首先，我們有一個處於I期臨床試驗的患者，他的CMAX是CMAX的三倍，AUC約為CUC的九倍。這還是單劑量的。如果代謝較差的人出現副作用──例如頭暈、臉紅之類的，那麼標籤上會提示你採取與百憂解類似的措施。如果你開始出現這些副作用，就應該停藥，因為你可能是代謝較差的人。然後，他們可以去做基因檢測，看看是否還能繼續服用。

That's normally how this works. If we don't see any adverse events for this population, then it's probably not much that would have to go into the label. And there's a fair number of people going into this project, so we should have a very good idea.

通常情況下就是這樣的。如果我們沒有發現這類族群有任何不良反應，那麼標籤上可能就不需要增加太多內容了。而且參與這個計畫的人也不少，所以我們應該能大致了解。

Then the other thing you always want to know is when you get a very high exposure, is what happens to the QT, and first of all, we'll be doing pretty intensive EKG monitoring in this particular study. And this high exposure becomes the high exposure arm for the QT study. And there, we would use -- we'd simply use higher concentrations topically to mimic this.

另一件你一直想知道的事情是，當你接受非常高的劑量時，QT 間期會發生什麼變化？首先，我們將在這項特定研究中進行非常密集的心電圖監測。這種高劑量暴露將成為 QT 間期研究的高劑量暴露組。我們會使用—我們只是局部使用更高濃度的藥物來模擬這種情況。

Okay, great. That's helpful. Thanks very much.

好的，太好了。這很有幫助。非常感謝。

Michael Mullen, OPN.

邁克爾·馬倫，OPN。

Hi, Dr. Ellison. Congratulations on the progress. I have two questions for you. Firstly, in reading the 10-Q and listening to David's presentation, we noticed that you're doing a lot of activity and spent a lot of money on activities that many other biotech companies would wait for these clinical results first. I want to get your thoughts on that as to why you guys are doing that now.

您好，Ellison博士。祝賀您取得進展。我有兩個問題想問您。首先，在閱讀10-Q和聽David的演講時，我們注意到您開展了很多活動，並在這些活動上投入了大量資金，而許多其他生物技術公司會先等待臨床結果。我想聽聽你們對此的看法，為什麼你們現在要這樣做。

And then secondly, now that the reports of the two products have flip-flopped, do you see any advantage in the anal fissure study reporting out first?

其次，現在兩種產品的報告已經發生了變化，您是否認為首先發布的肛裂研究報告有什麼優勢？

Well, thanks very much, Mike. Let me take the first question, which is a very good question.

好的，非常感謝，麥克。我來回答第一個問題，這個問題問得非常好。

First of all, there's a couple of ways of looking at this, whether you're big pharma or small pharma or biotech. One is you can say, you know, I'm going to minimize the risk of the study being negative, and I'm going to spend as little as possible and do as little as possible until I get the results, then I'll invest. That's kind of called White Space in big pharma that, you know, time you then have to spend after you get the data to really optimize the product.

首先，無論你是大型製藥公司、小型製藥公司或生技公司，都可以從幾個角度來看這個問題。一種是，你可以說，你知道，我要盡量降低研究結果為陰性的風險，我會盡可能少花錢，少做事，直到我得到結果，然後我才會投資。這在大型製藥公司裡被稱為“空白期”，你知道，在獲得數據後，你必須投入時間來真正優化產品。

The other way of looking at it is, we could do whatever we can do that makes sense to optimize the value of the asset when we get the data. And that's, in fact, what we're doing. Having said that, in the event that the trial is negative or there's a big problem with the drug, we do have plenty of cash left to continue to develop the other products. So we have made a very conscious decision to do what we can now that, in terms of sensible activities -- like the PK buying down the asset, doing the survey now, et cetera -- to enhance the potential value of the asset should the trial be positive.

換個角度來看，我們可以盡一切可能，在獲得數據後優化資產的價值。事實上，我們也正在這麼做。話雖如此，如果試驗結果呈陰性，或者藥物存在重大問題，我們仍然有足夠的現金來繼續開發其他產品。因此，我們非常謹慎地決定，盡我們所能，採取一些合理的措施——例如藥物動力學（PK）收購資產、立即進行調查等等——以便在試驗結果呈陽性時提升資產的潛在價值。

Now as to your other question, the potential change that anal fissure could report out first before hemorrhoids, it's very interesting. Anal fissure is a product that we would anticipate being filed, and hopefully, getting approved prior to the hemorrhoid product. So there is that aspect. And so that, assuming that's positive would be, I think, helpful in terms of the confidence in the Company. But I really don't see very much difference. I think the most important thing is that they're going to report out quite close together.

至於你的另一個問題，肛裂治療藥物可能先於痔瘡治療藥物先報告，這很有趣。我們預計肛裂治療藥物會先提交申請，並預計在痔瘡治療藥物之前獲得批准。所以確實存在這樣的情況。因此，假設這是正面的，我認為將有助於增強人們對公司的信心。但我真的看不出有什麼太大的差別。我認為最重要的是，它們的報告時間會非常接近。

Thank you.

謝謝。

[Michael Higgins], a private investor.

[麥可·希金斯]，一位私人投資者。

Thanks for taking my call. This continues to strike me -- the hemorrhoid market is an interesting opportunity for GI's and that's one of the takeaways from this survey work. But I had another couple of questions on Princeton.

感謝您接聽我的電話。這件事一直讓我印象深刻——痔瘡市場對胃腸道來說是一個有趣的機會，這是本次調查的收穫之一。不過我還有幾個關於普林斯頓的問題。

Had they done -- I know they worked 9 of 10 major pharmas, but have they done other GI work in the past? And if so, is there any kind of a benchmark you can take away from -- on their accuracy?

他們做過嗎？我知道他們和10家大型製藥公司中的9家合作過，但他們以前做過其他胃腸道疾病的檢測嗎？如果做過，有什麼基準可以參考嗎？他們的準確性如何？

That's a very good question. And I don't recall right now, but I'll have a look at that. We were impressed by the fact that they did the LOVAZA forecast, which was a very interesting market, that there was a lot of mixed opinions about how big that would be and how small that would be. And they got that right within about 2.5%. And that was one where you had a large consumer component, that kind of thing.

這是個非常好的問題。我現在記不太清楚，但我會看看。他們對LOVAZA的預測給我們留下了深刻的印象，這是一個非常有趣的市場，人們對其規模大眾說紛紜。最終，他們的預測準確率在2.5%左右。而且，這是一個消費者佔比很大的市場。

To me -- it's a good question, Mike -- but to me, the most important thing was how are they on markets that nobody knows much about, or product concepts that are very new or never really been done before? And where there's a very meaningful consumer component. That is to say, they're symptom-driven or consumer-driven. And LOVAZA was an interesting one. That's the one that I thought was the most compelling. But I think you've raised a good point and I'll go back and look. We did look at this; I just can't quite recall.

對我來說──麥克，這是個好問題──但對我來說，最重要的是它們如何進入那些鮮為人知的市場，或是那些非常新穎或從未真正實現的產品概念？以及在哪些方面存在著非常重要的消費者因素。也就是說，它們是症狀驅動的，或者說是消費者驅動的。 LOVAZA 就是一個很有意思的例子。我認為它最引人注目。但我認為你提的很有道理，我會回頭再看看。我們確實研究過這個問題；我只是記不太清楚了。

Okay. Also, did you mention there's more survey information coming from this as well?

好的。另外，你有沒有提到，這裡面還有更多的調查資訊？

Oh, we've got hundreds and hundreds and hundreds of tables on the consumers and that's even before the cross tabs. And with respect to the physician data, we haven't even got the tables from that yet. And that's going to be quite large and detailed as well. Because there, we exposed people to multiple product concepts. So -- different levels of efficacy, et cetera. So that's going to be quite fascinating. So we're going to have a lot more data going forward.

哦，我們已經有成百上千張關於消費者的表格了，這還是在交叉表之前。至於醫生數據，我們甚至還沒有從中得到表格。而且這些數據也會非常龐大和詳細。因為我們在那裡向人們展示了多種產品概念，包括不同程度的功效等等。這將會非常令人著迷。所以我們未來將會擁有更多的數據。

Is that the kind of info we could see a DDW? Or how do you expect to provide that?

DDW 能提供這類資訊嗎？或者說，你們打算如何提供這些資訊？

You know, I think the natural history -- first of all, the fact that you have a 10,000 consumer survey and you get an idea of a natural history. And in there also, which we still are looking at, is things like recurrence, chronicity, all kinds of information about their symptoms. And a lot more color also on this response to invasive treatments -- who gets the recurrence, who doesn't; by severity and history and so on. All of that we think is a great thing to put up to DDW. And we're going to certainly look at trying to get something in if we can.

你知道，我認為自然病程－首先，你對1萬名消費者進行了調查，你就能大致了解他們的自然病程。此外，我們仍在研究復發率、慢性病程以及各種症狀資訊。此外，我們還將更詳細地描述對侵入性治療的反應——哪些人會復發，哪些人不會；根據病情嚴重程度和病史等等。我們認為所有這些都值得提交給DDW。如果可以的話，我們一定會努力將這些資訊納入其中。

Okay. On 309's enrollment, you mentioned there's some exclusion criteria that may have pushed back or that seemed to contribute to the pushback in the completion of the enrollment. Can you give us a bit more on that? Is it more related to the patient type? Or more to the requirement for two-day consecutive hemorrhoids?

好的。關於309號病例的入組，您提到一些排除標準可能阻礙了入組，或者似乎導致了入組過程的延遲。能否詳細介紹一下？這與患者類型有關，還是與連續兩天痔瘡發作的要求有關？

It's actually half and half, pretty much. I mean, not precisely. So the need for having meaningful symptoms, that is to say, two days consecutive symptoms, so we can see a meaningful response -- that had a reasonable amount to do with it. And people actually, because of that, stay in screening for usually up to about three weeks to a month in order to experience that. And that actually added to the time lines, too.

實際上差不多是一半一半，我的意思是，不完全是。所以需要出現有意義的症狀，也就是說，連續兩天出現症狀，這樣我們才能看到有意義的反應——這在很大程度上與此有關。實際上，正因為如此，人們通常需要接受長達三週到一個月的篩檢才能體驗到這種效果。這其實也延長了篩檢時間。

But the other part, which actually was a meaningful contribution, was having had a history of depression or having a history of depression was a big one. Depression, SSRIs was a big one. And those we expect to get a lot narrower once we have our DDI.

但另一部分，其實也是一項有意義的貢獻，那就是曾經有過憂鬱症病史，或是曾經服用過憂鬱症藥物，這其中很大一部分原因。憂鬱症和SSRIs（選擇性5-羥色胺再攝取抑制劑）是其中很重要的一部分。而一旦我們擁有了DDI，我們預期這些因素的範圍就會大大縮小。

And the chronic diseases were obviously important -- a lot of these people are over the age of 50, and so they will have these other common and chronic diseases, which we certainly intend to include going forward, and the FDA would certainly like us to include. So -- and as I said, once we're out of an open label, one-year extension, then we're into double-blind methodology purely, we're certainly going to bring those people in. And that should make a difference in future studies.

慢性病顯然很重要——這些人很多都超過50歲，所以他們會患有其他常見疾病和慢性疾病，我們當然打算在未來將這些疾病納入研究範圍，FDA也肯定希望我們這樣做。所以——正如我所說，一旦我們結束為期一年的開放標籤試驗，然後完全採用雙盲試驗方法，我們肯定會將這些患者納入研究範圍。這應該會對未來的研究產生影響。

Okay. That's helpful. And also as you're used to by now, I'm always asking the timing -- any insights you can provide for us on German study and that bioequivalency data for --?

好的。這很有幫助。而且，正如您現在習慣的那樣，我總是詢問時間——您能為我們提供關於德國研究和生物等效性數據的任何見解嗎？

Oh, yes. So the German study in terms of the publication, we're waiting to hear back from the Journal any day now. And first of all, they have to accept it; then we'll have to see how many review rounds we're going to get. But assuming one review round, then we're still looking at publishing this before New Year's.

哦，是的。所以，關於德國研究的發表，我們正在等待期刊的回應。首先，他們必須接受它；然後我們還要看看要經過多少輪審查。假設只有一輪審查，我們仍然希望在新年之前發表。

On the preclinical pharmacology, that's probably going to be in the first quarter next year.

關於臨床前藥理學，這可能會在明年第一季進行。

Okay. And then one last quick one here. Can you provide us any guidance on the remaining cost of the Phase 3 now until completion?

好的。最後還有最後一個問題。您能否提供一些關於第三階段目前到完工的剩餘成本的指導？

To be honest, that's a movable piece under most scenarios. As David said, we're good till early 2014. But here's what's going to drive those scenarios. For example, what the recurrence rate is, because that's going to drive the size of the double-blind recurrence trial, at least with respect to the number of people we have to treat open label for the first episode.

說實話，在大多數情況下，這都是一個不確定因素。正如David所說，我們可以撐到2014年初。但以下因素將決定這些情況。例如，復發率是多少，因為這將決定雙盲復發試驗的規模，至少就首發病例開放標籤治療的人數而言。

The actual effect size between placebo and whichever regimen we choose is going to determine the size of the next Phase 2. And those are really the two big drivers. So there's a fairly large range. We think most scenarios, as I said, allow us to complete those trials by early into the first half of 2014. But as I said, it's very hard to say; as I said, most scenarios would allow us to do that.

安慰劑和我們選擇的任何方案之間的實際效果大小將決定下一階段二期臨床試驗的規模。這確實是兩個重要的驅動因素。所以範圍相當大。正如我所說，我們認為大多數情況下，我們可以在2014年上半年初完成這些試驗。但正如我所說，這很難說；正如我所說，大多數情況下我們都能做到這一點。

And it's kind of fascinating actually, looking at the costs, et cetera, that we're spending on this trial and how we did it. We found a way to -- we were looking at ways that we could actually reduce the actual unit costs over the next studies, too. So we're working on that. And all those things add up to what the actual cost would be. I really can't give you a number now until I see the data.

看看我們在這次試驗上花費的成本等等，以及我們是如何做到的，這真的很有趣。我們找到了一種方法——我們也在尋找方法，在接下來的研究中真正降低實際單位成本。所以我們正在努力。所有這些加起來就是實際成本。在看到數據之前，我現在真的無法給你一個確切的數字。

Okay, we can follow-up offline later. I appreciate the time, guys. I'll just jump back in the queue. Thanks.

好的，我們可以稍後線下跟進。非常感謝大家的時間。我還是回到隊列吧。謝謝。

(Operator Instructions). Mike King, Rodman.

（操作員指示）。麥克金，羅德曼。

Thanks for taking the questions. Just wanted to maybe get a bit of follow-up on the survey and two aspects of it, if you would. First of all, is there any way to understand how promotion-sensitive a product might be based on Princeton Brand Econometrics? I mean, you said that they got within 2.5% (multiple speakers) of the LOVAZA actuals.

感謝您回答這些問題。如果可以的話，我想跟進一下這項調查，以及調查中的兩個方面。首先，根據普林斯頓品牌計量經濟學，有什麼方法可以了解產品對促銷的敏感度嗎？我的意思是，您說他們的實際銷售額與 LOVAZA 的實際銷售額相差在 2.5% 以內（多位發言者）。

Oh, yes. There is (multiple speakers) --

哦，是的。 （多位發言者）——

How did they get there? And what were the factors that drove that?

他們是如何實現這目標的？又有哪些因素促成了這目標的實現？

Yes, so this is very important. So their model is very, very good this way. So basically, you build a basic model based on all these responses. And you can dial in on the physician's side, your field force at a fair number of -- at fairly precise levels. And you can dial in your -- not just your spend but your media markets. And most importantly, the frequency of your DTC campaign. And once you dial in those numbers, you'll get a forecast. And a very important part of the forecast is the ramp rate, which many people don't do. That is to say, the speed at which you're going to go up.

是的，這非常重要。他們的模型在這方面非常非常好。基本上，你可以根據所有這些回饋建立一個基礎模型。然後，你可以從醫生的角度，以及你的外勤人員的角度，以相當精確的水平進行調整。你還可以調整你的支出，包括你的媒體市場。最重要的是，你的DTC行銷活動的頻率。一旦你輸入了這些數字，你就會得到一個預測。預測中一個非常重要的部分是上升率，很多人沒有這麼做。也就是說，你要上升的速度。

So they do all those things. And so those we will be able to get. And probably -- we'll probably start doing that once we get the data and we plug in the actual effect sizes that we get from this trial, to be able to really gauge the physician responses.

所以他們做了所有這些事情。這些我們都能得到。而且，一旦我們獲得數據，並把從這次試驗中獲得的實際效果大小代入進去，我們很可能就會開始這樣做，以便能夠真正衡量醫生的反應。

Okay. Well, thanks for the elaboration there. And then to -- I guess, to further drill down on the addressable versus the potential market, were there questions in this survey that had to do with some of the other concomitant illness that might make someone either unwilling or unable to acquire the product?

好的。嗯，謝謝你的詳細闡述。然後——我想，為了進一步深入探討目標市場和潛在市場，這項調查中是否有一些問題與其他一些可能導致人們不願或無法購買該產品的伴隨疾病有關？

Well, we have some very basic things. We have a list of about eight conditions that we put in there. And right now, there's a lot of assumptions about people with depression and SSRIs. And without the DDI data, I'm not sure what their ability to take the product is going to be. But with respect to all the other conditions, except for Parkinson's and stroke, where there's going to be an application problem, we don't really see necessarily that there would be any provision. So the one that the DDI studies will tell us about a lot more is people with depression on SSRIs.

嗯，我們有一些非常基本的情況。我們列出了大約八種情況。目前，關於憂鬱症患者和SSRIs有許多假設。如果沒有DDI的數據，我不確定他們服用該產品的能力如何。但對於所有其他情況，除了帕金森氏症和中風（這兩種疾病在應用方面有問題）之外，我們並不認為會有任何規定。因此，DDI的研究將告訴我們更多關於服用SSRIs的憂鬱症患者的資訊。

Okay. And then one other quick one and I'll jump back. The financial guidance, the 2014, does that assume any pre-market activities at all? Pre-launch activities?

好的。然後我再快速問一個問題，然後我就回到正題。 2014年的財務指引是否涵蓋了任何上市前活動？上市前活動？

(multiple speakers) No, it does not. It does not, no. And it's based on -- as I said, it's based on the data we observed in the German trials, the effect size, some variants around that, and certain assumptions around recurrence.

（多位發言者）不，事實並非如此。事實並非如此。它是基於——正如我所說，它基於我們在德國試驗中觀察到的數據、效應大小、相關的一些變數以及關於復發的某些假設。

Okay. Thanks for taking my questions.

好的。感謝您回答我的問題。

Sebastian Marti, National Securities.

塞巴斯蒂安·馬蒂，國家證券公司。

Good morning, Dr. Thanks for taking the call. The question is, when and where can we expect to see a list of which institutions own the common stock of interest?

早上好，博士。感謝您接聽電話。問題是，我們何時何地可以看到持有相關普通股的機構名單？

And second part is, which dates in the next six to 12 months do you expect inflection points on the price of the stock?

第二部分是，您預計未來 6 到 12 個月內哪些日期會出現股票價格的轉捩點？

So with respect to the institutions, some of them have filed 13 G's -- that was Fidelity, [Jenison], and RA Capital. And others should be coming out with their 13 F's November 15, and you'll be able to see it from there.

就機構投資者而言，其中一些機構已經提交了13家G類公司，包括富達、[Jenison]和RA Capital。其他機構的13家F類公司應該會在11月15日公佈，屆時大家就能看到結果了。

With respect to inflection points and the stock, as I said, we've got this publication coming out from the German trial. And basically -- and then we have the completion of enrollment of the anal fissure trial in January. Then the completion enrollment of the hemorrhoid trial in April. And then the data start reporting out in May and June.

關於拐點和庫存，正如我所說，我們已經發布了德國試驗的結果。基本上——肛裂試驗的招募工作將在一月完成。痔瘡試驗的招募工作將在四月完成。然後，數據將在五月和六月開始公佈。

Excellent, thank you.

非常好，謝謝。

Thank you. I'm showing no further questions in queue at this time. I would like to turn the call back over to Dr Ellison for any further remarks.

謝謝。目前隊列中沒有其他問題了。我想把電話轉回給艾里森博士，請他發表進一步的評論。

Okay. Thank you very much for dialing into this call. It's so early in the morning, I really appreciate your interest and your support of the Company. And I look forward to future calls with you, and I'm very happy to take your questions after the call.

好的。非常感謝您撥通電話。這麼早，我非常感謝您的關注和對公司的支持。我期待下次與您通話，也很樂意在通話結束後回答您的問題。

And I just want to just reiterate that the slide deck I've used is in our 8-K, and later today will be posted on our website. Okay? So, thanks very much, everyone, and have a wonderful day.

我只想重申一下，我使用的幻燈片已經收錄在我們的8-K文件中，今天晚些時候會發佈到我們的網站上。好嗎？非常感謝大家，祝大家有美好的一天。

Ladies and gentlemen, thank you for your participation. That concludes the conference. You may disconnect. And have a wonderful day.

女士們，先生們，感謝各位的參與。會議到此結束。您可以斷開連線了。祝您擁有美好的一天。