Achieve Life Sciences Inc (ACHV) 2011 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the OncoGenex fourth quarter and year end 2011 earnings conference call. My name is Javon. At this time all participants are in a listen-only mode. Later we will conduct a question and answer period, and instructions will follow at that time. (Operator Instructions). As a reminder, this conference call is being recorded.

女士們、先生們，下午好，歡迎參加 OncoGenex 2011 年第四季度和年終收益電話會議。我叫賈文。此時所有參與者都處於只聽模式。稍後我們將進行問答環節，屆時會有說明。 （操作員說明）。謹此提醒，本次電話會議正在錄音中。

At this time I would like to turn the call over to Susan Specht, Director of Investors Relations with OncoGenex Pharmaceuticals. Please go ahead.

現在我想將電話轉給 OncoGenex Pharmaceuticals 投資者關係總監 Susan Specht。請繼續。

Thank you. Thanks, everyone, for joining us. With me today from OncoGenex are Scott Cormack, Chief Executive Officer; Michelle Burris, Chief Financial Officer. Also on the call are Cindy Jacobs, Chief Medical Officer; Cameron Lawrence, Principal Accounting Officer; and Jaime Welch, VP of Marketing and Corporate Communications.

謝謝。謝謝大家加入我們。今天和我在一起的還有來自 OncoGenex 的首席執行官 Scott Cormack；米歇爾·伯里斯，首席財務官。參加電話會議的還有首席醫療官辛迪·雅各布斯 (Cindy Jacobs)；卡梅倫·勞倫斯，首席會計官；以及營銷和企業傳播副總裁 Jaime Welch。

Before we begin I would like to remind everyone that today's conference call contains forward-looking statements based on current expectations. These statements are only predictions, and actual results may vary materially from those projected. Refer to OncoGenex's documents filed with the SEC concerning factors that could affect the Company, copies of which are available on the website.

在我們開始之前，我想提醒大家，今天的電話會議包含基於當前預期的前瞻性陳述。這些陳述僅是預測，實際結果可能與預測存在重大差異。請參閱 OncoGenex 向 SEC 提交的有關可能影響公司的因素的文件，這些文件的副本可在網站上找到。

I will now turn the call over to Scott Cormack, President and CEO, OncoGenex.

我現在將把電話轉給 OncoGenex 總裁兼首席執行官 Scott Cormack。

Thank you, Susan. Good afternoon, and thank you for joining us. As announced earlier today, we and Teva amended our collaboration agreement, enhancing our custirsen development plans in advanced prostate cancer. We believe these changes optimize custirsen's ability to succeed in the rapidly changing prostate cancer landscape.

謝謝你，蘇珊。下午好，感謝您加入我們。正如今天早些時候宣布的，我們和 Teva 修改了我們的合作協議，加強了我們在晚期前列腺癌方面的 custirsen 開發計劃。我們相信這些變化將優化 custirsen 在快速變化的前列腺癌領域取得成功的能力。

As part of the amendment, we and Teva will be initiating a few Phase 3 study to evaluate an overall survival benefit of custirsen when combined with the second line chemotherapy cabazitaxel for patients with castrate resistant prostate cancer, or CRPC. We believe the addition of this study to the custirsen development plan is well aligned with the anticipated changes to the treatment continuum. We believe that chemotherapy will remain a standard of care in advanced prostate cancer, especially given the recent announcement and data, which anticipate will shift the utilization of abiraterone into the chemotherapy-naive patient operation.

作為修正案的一部分，我們和 Teva 將啟動一些 3 期研究，以評估 custirsen 與二線化療卡巴他賽聯合治療去勢抵抗性前列腺癌 (CRPC) 患者的總體生存獲益。我們相信將這項研究添加到 custirsen 開發計劃中與治療連續體的預期變化非常一致。我們相信，化療仍將是晚期前列腺癌的標準治療方法，特別是考慮到最近的公告和數據，預計阿比特龍的使用將轉移到未經化療的患者手術中。

Additionally, while data is still pending for MDV3100, we expect it will be sequenced earlier in the treatment continuum. Custirsen will now be evaluated to improve the survival outcomes for existing treatment options in first and second line chemotherapy, where once again there are limited treatment options for patients.

此外，雖然 MDV3100 的數據仍在等待中，但我們預計它將在治療連續體的早期進行測序。現在將對 Custirsen 進行評估，以改善一線和二線化療中現有治療方案的生存結果，而患者的治療方案再次有限。

The new Phase 3 study is designed to show a survival benefit with 85% power based on hazard ratio of 0.75, or approximate 25% increase in survival time when custirsen is combined with cabazitaxel for second line chemotherapy. The new study, which we expect to begin in the second half of 2012, will be conducted in lieu of the prostate cancer SATURN study, our study that was designed with a primary end point of measuring a durable pain palliation benefit for custirsen in CRPC patients. As previously discussed, the SATURN trial continued to experience difficulties recruiting a sufficient number of patients in a timely manner due to the eligibility criteria requiring stable baseline pain and analgesic use in men who have end stage cancer pain.

新的 3 期研究旨在顯示基於 0.75 風險比的 85% 的生存獲益，即當 custirsen 與卡巴他賽聯合用於二線化療時，生存時間增加約 25%。我們預計將於 2012 年下半年開始的這項新研究將取代前列腺癌 SATURN 研究，該研究的主要終點是測量 custirsen 對 CRPC 患者的持久疼痛緩解效果。如前所述，SATURN 試驗在及時招募足夠數量的患者方面仍然遇到困難，因為資格標準要求患有末期癌症疼痛的男性具有穩定的基線疼痛和鎮痛劑的使用。

The shift in focus to a survival end point for our second Phase 3 trial in prostate cancer allows us to evaluate custirsen in a similar manner to the recently approved agents redefining the standard of care in this patient setting. This study will also provide survival data for custirsen in combination with cabazitaxel, whether cabazitaxel remains a second line chemotherapy for CRPC or is repositioned as first line chemotherapy based on future results of ongoing studies. We remain committed and still firmly believe in the importance of managing and improving prostate cancer related pain. This end point will be assessed in the new trial, but not as the primary end point.

我們第二次前列腺癌 3 期試驗將重點轉向生存終點，這使我們能夠以與最近批准的藥物類似的方式評估 custirsen，重新定義了該患者的護理標準。這項研究還將提供 custirsen 聯合卡巴他賽的生存數據，無論卡巴他賽仍然是 CRPC 的二線化療，還是根據未來正在進行的研究結果重新定位為一線化療。我們仍然致力於並堅信管理和改善前列腺癌相關疼痛的重要性。該終點將在新試驗中進行評估，但不作為主要終點。

Regarding our primary registration Phase 3 study SYNERGY, we continue to be very positive on the progress of this trial, which is evaluating the survival benefit for patients in the first line chemotherapy CRPC setting. As we can discussed before, FDA and EMA have indicated that a New Drug Application supported primarily by the results of SYNERGY alone would be acceptable. The New Drug Application would also contain the supportive randomized Phase 2 trial data, as well as additional safety data.

關於我們的主要註冊 3 期研究 SYNERGY，我們仍然對該試驗的進展非常積極，該試驗正在評估一線化療 CRPC 環境中患者的生存獲益。正如我們之前所討論的，FDA 和 EMA 已表示主要僅由 SYNERGY 結果支持的新藥申請是可以接受的。新藥申請還將包含支持性隨機 2 期試驗數據以及其他安全數據。

Results for SYNERGY survival primary end point are event driven. I believe that the timing for final analysis remains unchanged and anticipate that the specified number of events will be observed in the fourth quarter of 2013. We have increased the enrollment target of SYNERGY from 800 to 1,000 patients, which should further the potential for this trial to be reviewed by the regulatory agencies independent of additional Phase 3 studies. Importantly, even with the trial size increasing by 25%, OncoGenex and Teva plan to complete enrollment later this year as originally disclosed. Along with the increased number of patients, the hazard ratio has been revised from 0.725 to 0.75, providing a higher likelihood of achieving the target hazard ratio.

SYNERGY 生存主要終點的結果是事件驅動的。我相信最終分析的時間保持不變，並預計將在2013 年第四季度觀察到指定數量的事件。我們已將SYNERGY 的入組目標從800 名患者增加到1,000 名患者，這應該會進一步增強該試驗的潛力由監管機構獨立於其他第三階段研究進行審查。重要的是，即使試驗規模增加了 25%，OncoGenex 和 Teva 仍計劃按照最初披露的那樣在今年晚些時候完成入組。隨著患者數量的增加，風險比已從 0.725 修改為 0.75，實現目標風險比的可能性更高。

The recent updates to the SYNERGY study have been reviewed and accepted as part of an accept -- an amended SPA protocol by the FDA. As a reminder our financial commitment to the custirsen development program is limited to the $30 million advance reimbursement. After which Teva is responsible for all costs, including the increased number of patients for SYNERGY and the new second line chemotherapy trial, which at an estimated 630 patients, is substantially larger than the original SATURN trial.

SYNERGY 研究的最新更新已被審查並接受為 FDA 修訂的 SPA 協議的一部分。謹此提醒，我們對 custirsen 開發計劃的財務承諾僅限於 3000 萬美元的預付款。此後，Teva 負責所有費用，包括 SYNERGY 增加的患者數量和新的二線化療試驗，估計有 630 名患者，比原來的 SATURN 試驗要大得多。

Finally, we continue to work with Teva to finalize our development plans for custirsen in non-small cell lung cancer. As previously stated, I expect that we will initiate this program in second half of 2012 and will provide further updates in our subsequent communications.

最後，我們繼續與 Teva 合作，最終確定 custirsen 在非小細胞肺癌中的開發計劃。如前所述，我預計我們將在 2012 年下半年啟動該計劃，並將在後續溝通中提供進一步的更新。

To conclude on our custirsen update, we feel these changes further reinforce the commitments both Teva and OncoGenex have made to developing custirsen for patients suffering from advanced prostate cancer. The increased size of SYNERGY and the shift in focus to a survival trial for second line chemotherapy represents a substantial investment of time, personnel, and dollars by Teva, and we believe illustrates that custirsen remains a top priority within both organizations.

最後，我們認為這些變化進一步強化了 Teva 和 OncoGenex 為晚期前列腺癌患者開發 custirsen 的承諾。 SYNERGY 規模的擴大以及重點轉向二線化療生存試驗代表了 Teva 投入了大量的時間、人員和資金，我們相信這表明 custirsen 仍然是兩個組織內的首要任務。

I would like to now focus on some significant clinical developments with our second product candidate, OGX-427. As you may recall from previous discussions, OGX-427 is designed to reduce levels of the heat shock protein 27, or Hsp27. Overexpression of Hsp27 correlates to increased stage and grade in many types of cancer. It is also believed to be an important factor leading to the development of treatment resistance and is associated with negative clinical outcomes in various cancers.

我現在想重點關注我們的第二個候選產品 OGX-427 的一些重大臨床進展。您可能還記得之前的討論，OGX-427 旨在降低熱休克蛋白 27 或 Hsp27 的水平。 Hsp27 的過度表達與多種癌症的分期和分級增加相關。它還被認為是導致治療耐藥性發展的重要因素，並且與各種癌症的負面臨床結果相關。

Preclinical studies indicate that inhibition of Hsp27 increases tumor cell death rates and delays tumor growth. Hsp27 influences apoptosis through many pathways, including managing the burden of unfolded proteins within a cell, as well as interfering with IGF-1 and IL-6 signaling, to mention a few. These pathways are generally believed to be important contributors to cancer progression.

臨床前研究表明，抑制 Hsp27 會增加腫瘤細胞死亡率並延緩腫瘤生長。 Hsp27 通過多種途徑影響細胞凋亡，包括管理細胞內未折疊蛋白的負擔，以及乾擾 IGF-1 和 IL-6 信號傳導等。人們普遍認為這些途徑是癌症進展的重要因素。

At the 2012 ASCO GU symposium held last month in San Francisco, preliminary clinical data were presented on OGX-427 in both prostate and bladder cancer. The first study presented reported preliminary data on OGX-427 in chemotherapy-naive patients with metastatic CRPC. In this Phase 2 study patients randomized to receive OGX-427 plus prednisone at the treatment arm, or prednisone alone as a control arm. Upon disease progression, patients who receive prednisone alone are allowed to cross over to thetreatment arm. The goal of this study is to evaluate the effect of OGX-427 on disease progression and tumor response markers such as PSA and circulating tumor cells.

上個月在舊金山舉行的 2012 年 ASCO GU 研討會上，公佈了 OGX-427 在前列腺癌和膀胱癌中的初步臨床數據。第一項研究報告了 OGX-427 在未接受化療的轉移性 CRPC 患者中的初步數據。在這項 2 期研究中，患者隨機接受 OGX-427 加潑尼松治療組，或單獨接受潑尼松作為對照組。當疾病進展時，僅接受潑尼松治療的患者可以轉到治療組。本研究的目的是評估 OGX-427 對疾病進展和腫瘤反應標誌物（如 PSA 和循環腫瘤細胞）的影響。

In the first 32 patients randomized, 17 patients received the OGX-427 and prednisone treatment, and 15 patients received prednisone alone. Compared to patients in the control arm, over twice as many of the patients who received the OGX-427 treatment were progression free at 12 weeks. At the time of data presentation, eight patients in the OGX-427 treatment arm and nine in the control arm had baseline measurable disease.

在前 32 名隨機分組的患者中，17 名患者接受 OGX-427 和潑尼松治療，15 名患者單獨接受潑尼松治療。與對照組患者相比，接受 OGX-427 治療的患者在 12 週時無進展的患者人數是對照組的兩倍多。截至數據發佈時，OGX-427 治療組的 8 名患者和對照組的 9 名患者患有基線可測量疾病。

38% of patients who received OGX-427 had a partial response compared to 0% of the patients in the control arm. In regards to PSA response, 76% of the patients in the OGX-427 treatment arm experienced an overall decline in PSA compared to 53% of the patients in the control arm. 41% of the patients in the treatment arm experienced a greater than 50% decline in PSA, versus 20% of the patients in the control arm.

接受 OGX-427 治療的患者中有 38% 出現部分緩解，而對照組患者的這一比例為 0%。關於 PSA 反應，OGX-427 治療組中有 76% 的患者 PSA 總體下降，而對照組患者的這一比例為 53%。治療組中 41% 的患者 PSA 下降超過 50%，而對照組中這一比例為 20%。

OGX-427 treatment appeared well tolerated, with adverse events -- primarily grade one or two -- reported in both arms. Grade three or higher adverse events were reported in 31% of patients in the OGX-427 treatment arm and 25% in the control arm. As expected, OGX-427 infusion reactions occurred and were primarily grade one or two. We continue to enroll patients in this Phase 2 study and anticipate that the results will provide us with further insights and better understanding of the potential benefit of Hsp27 inhibition in prostate cancer.

OGX-427 治療似乎具有良好的耐受性，雙臂均報告有不良事件（主要是一級或二級）。 OGX-427 治療組和對照組分別有 31% 和 25% 的患者報告了三級或以上不良事件。正如預期的那樣，出現了 OGX-427 輸注反應，並且主要為一級或二級反應。我們將繼續招募患者參與這項 2 期研究，並預計結果將為我們提供進一步的見解和更好地了解 Hsp27 抑制在前列腺癌中的潛在益處。

As a reminder, Hsp27 also influences the androgen receptor, a key driver of prostate cancer progression. The PSA responses seen in this study strengthen our resolve that OGX-427 has the ability to suppress androgen receptor activity via blocking its translocation to the nucleus and causing proteasomal degradation of the receptor. Additional strategies to prevent androgen receptor driven progression continue to be a need and may be particularly important for patients experiencing a rising PSA while on abiraterone or MDB3100. Therefore, as announced at the ASCO GU conference, we will be initiating a Phase 2 study of OGX-427 in combination with abirateronelater this year.

提醒一下，Hsp27 還會影響雄激素受體，雄激素受體是前列腺癌進展的關鍵驅動因素。本研究中看到的 PSA 反應增強了我們的決心，即 OGX-427 具有通過阻止雄激素受體易位到細胞核並引起受體蛋白酶體降解來抑制雄激素受體活性的能力。仍然需要防止雄激素受體驅動的進展的其他策略，並且對於在阿比特龍或 MDB3100 期間經歷 PSA 升高的患者尤其重要。因此，正如在 ASCO GU 會議上宣布的那樣，我們將於今年啟動 OGX-427 與 abirateronelater 聯合用藥的 2 期研究。

Today's announcement regarding abiraterone's favorable data in the CRPC chemo-naive patient population provides additional clarity on this study design. Recall our expectation is that by combining OGX-427 with abiraterone, we will be able to improve upon the clinical benefit provided by abiraterone alone. We look forward to sharing additional details on this trial in the near future.

今天關於阿比特龍在 CRPC 化療初治患者群體中的有利數據的公告為這項研究設計提供了額外的清晰度。回想一下，我們的期望是，通過將 OGX-427 與阿比特龍結合使用，我們將能夠改善阿比特龍單獨提供的臨床益處。我們期待在不久的將來分享有關該試驗的更多細節。

The second study presented was a Phase 1 study evaluating OGX-427 infused directly into the bladder of patients with superficial or muscle invasive bladder cancer prior to tumor excision. This trial was designed to evaluate the effects of OGX-427 on Hsp27 expression and tumor response rates. Of the 15 patients treated with OGX-427, approximately one third of patients had complete responses with no pathologic evidence of disease observed in post-surgical tissue following only four doses of OGX-427 administered over an eight day period. The preliminary results also demonstrated the trend towards decreased levels of Hsp27 and increased tumor cell death rates.

提出的第二項研究是一項 1 期研究，評估在腫瘤切除前將 OGX-427 直接注入淺表或肌層浸潤性膀胱癌患者的膀胱。該試驗旨在評估 OGX-427 對 Hsp27 表達和腫瘤反應率的影響。在接受 OGX-427 治療的 15 名患者中，大約三分之一的患者在八天內僅服用四劑 OGX-427 後出現完全緩解，並且在術後組織中沒有觀察到疾病的病理證據。初步結果還表明 Hsp27 水平下降和腫瘤細胞死亡率增加的趨勢。

In the OGX-427 treated patients who experienced a complete response, the absence of residual disease made it difficult to fully assess treatment effects on Hsp27 levels. Therefore the analysis was based mainly on the remaining patients who had evaluable tumor tissue. We will continue to enroll patients with larger tumors to assess the effect of higher doses of OGX-427 on Hsp27 levels in patients with bladder cancer. While it may decrease the complete response rate, we believe it is important to capture the effect of OGX-427 on Hsp27 expression in tumor cells within the bladder.

在經歷完全緩解的 OGX-427 治療患者中，由於沒有殘留疾病，因此很難全面評估對 Hsp27 水平的治療效果。因此，分析主要基於具有可評估腫瘤組織的其餘患者。我們將繼續招募腫瘤較大的患者，以評估較高劑量的 OGX-427 對膀胱癌患者 Hsp27 水平的影響。雖然它可能會降低完全緩解率，但我們認為捕獲 OGX-427 對膀胱內腫瘤細胞 Hsp27 表達的影響非常重要。

As we have discussed before, bladder cancer represents an important unmet need. This year in the US alone an estimated 74,000 new cases of bladder cancer are expected to be diagnosed, and approximately 15,000 people are expected to die from the disease. Over the last several years very few medical advances have improved patient outcomes, specifically extending survival.

正如我們之前討論的，膀胱癌代表了一個重要的未滿足的需求。僅今年在美國，預計將診斷出 74,000 例膀胱癌新病例，並預計約有 15,000 人死於該病。在過去的幾年裡，很少有醫學進步能夠改善患者的治療結果，特別是延長生存期。

In addition to the Phase I bladder cancer study just reviewed, we continue to enroll patients to our international randomized Phase 2 trial of OGX-427 in approximately 180 patients with metastatic bladder cancer. The primary objective of this study is to evaluate a potential survival benefit when adding OGX-427 to first line gemcitabine and cisplatin chemotherapy. The trial will be conducted as an event driven trial such that the final analysis will have 80% power to show a critical hazard ratio of approximately 0.66 to 0.71. The survival end point and results of the study should inform us of future requirements and potential success of Phase 3 trials.

除了剛剛回顧的 I 期膀胱癌研究外，我們還繼續招募患者參加 OGX-427 的國際隨機 2 期試驗，該試驗涉及約 180 名轉移性膀胱癌患者。本研究的主要目的是評估將 OGX-427 添加到一線吉西他濱和順鉑化療中時的潛在生存獲益。該試驗將作為事件驅動試驗進行，最終分析將有 80% 的功效顯示大約 0.66 至 0.71 的臨界風險比。生存終點和研究結果應告知我們未來的要求和第三階段試驗的潛在成功。

At this time I will turn the call over to Michelle, who will provide an overview of the fourth quarter financial results. Michelle?

此時，我會將電話轉給米歇爾，她將概述第四季度的財務業績。米歇爾？

Thank you, Scott. As we ended 2011 with approximately $65 million in cash, cash equivalents and short term investments, that is above our guidance of $58 million to $62 million. We estimate that these funds, combined with any reimbursements due from Teva under the collaboration agreement, will be sufficient to conduct our development plans into 2014. Please keep in mind that once the remaining advanced reimbursement from Teva is drawn upon, which equals $18.3 million at the year end 2011, all comps associated with the custirsen development plan will be reimbursed by Teva on a quarterly basis. We expect the $18.3 million to be drawn upon by the end of this year.

謝謝你，斯科特。截至 2011 年末，我們擁有約 6500 萬美元的現金、現金等價物和短期投資，高於我們 5800 萬至 6200 萬美元的指導值。我們估計，這些資金，加上 Teva 根據合作協議應付的任何補償，將足以執行我們到 2014 年的開發計劃。請記住，一旦 Teva 剩餘的預付款（相當於 1830 萬美元）被動用，到2011年底，所有與custirsen 開發計劃相關的補償費用將由Teva 每季度報銷。我們預計 1830 萬美元將於今年年底動用。

Revenue for the fourth quarter and year ended 2011 decreased to $1.2 million and $5.5 million respectively. That compares with $2.3 million and $13.6 million in 2010. The decreases in 2011 are primarily due to lower revenue earned through the Company's strategic collaboration with Teva.

2011 年第四季度和全年的收入分別下降至 120 萬美元和 550 萬美元。相比之下，2010 年為 230 萬美元和 1,360 萬美元。2011 年的下降主要是由於公司與 Teva 的戰略合作所獲得的收入減少。

Total operating expenses for the fourth quarter and year ended 2011 decreased to $9.2 million and $27.8 million respectively. That compares with $4.2 million and $28.4 million in 2010. The 2011 decreases in operating expenses were due to a $4 million noncash restructuring expense that we recorded in 2010, which was offset primarily by higher OGX-427 manufacturing and clinical trial costs.

2011 年第四季度和全年的總運營支出分別減少至 920 萬美元和 2,780 萬美元。相比之下，2010 年為420 萬美元和2840 萬美元。2011 年運營費用減少是由於我們在2010 年記錄的400 萬美元非現金重組費用，該費用主要被較高的OGX-427 製造和臨床試驗成本所抵消。

Net loss for the fourth quarter of 2011 and year ended 2011 increased to $9.6 million and $14.7 million, or $0.98 per diluted common share for the quarter and $1.51 for the year. That compares to $2.8 million and $12.6 million for the fourth quarter and year end 2010. This increase in net loss is the result again of the lower revenue recognized in connection with the collaboration agreement and the higher 427 manufacturing and clinical trial costs.

2011 年第四季度和 2011 年終了的淨虧損分別增至 960 萬美元和 1,470 萬美元，即該季度每股稀釋普通股虧損 0.98 美元，全年稀釋普通股虧損 1.51 美元。相比之下，2010 年第四季度和年底為 280 萬美元和 1260 萬美元。淨虧損的增加再次是由於與合作協議相關的收入減少以及 427 製造和臨床試驗成本增加所致。

Before completing our financial review, I would like to provide some guidance for 2012. Our guidance reflects our continued development of custirsen under the Teva agreement, as well as our proprietary asset, OGX-427, which is soon to be in three randomized Phase 2 studies. We anticipate net operating cash requirements for 2012 of between $40 million and $45 million, and expect to end 2012 with cash, cash equivalent investments and reimbursements from Teva of between $20 million and $25 million.

在完成我們的財務審查之前，我想為2012 年提供一些指導。我們的指導反映了我們根據Teva 協議對custirsen 的持續開發，以及我們的專有資產OGX-427，該資產很快將進入三個隨機階段 2學習。我們預計 2012 年的淨運營現金需求將在 4000 萬至 4500 萬美元之間，並預計到 2012 年底，Teva 的現金、現金等價物投資和報銷將在 2000 萬至 2500 萬美元之間。

The estimated increase in cash burn for 2012 reflects the higher anticipated cash requirements for the new Phase 3 overall survival study in second line chemotherapy in patients with CRPC, as well as a continuation of the randomized Phase 2 study of OGX-427 in first line metastatic bladder. Just to clarify, while we expect to burn between $40 million and $45 million in 2012, at least $18 million of that amount is remaining from the Teva advanced reimbursement and is expected to be spent by the end of this year. That means that our beginning cash balance of $65 million, net of the advanced reimbursement, is approximately $47 million, and that we believe is sufficient to conduct our operations into 2014.

2012 年現金消耗的估計增加反映了 CRPC 患者二線化療的新 3 期總體生存研究以及一線轉移性 OGX-427 隨機 2 期研究的繼續預期現金需求較高膀胱。需要澄清的是，雖然我們預計 2012 年將消耗 4000 萬至 4500 萬美元，但其中至少有 1800 萬美元來自 Teva 預付款，預計將在今年年底前支出。這意味著我們的期初現金餘額為 6500 萬美元，扣除預付款後，約為 4700 萬美元，我們相信這足以維持我們 2014 年的運營。

That completes our review, and with that I would now like to open up the line for any questions.

我們的審查到此結束，現在我想開通熱線詢問任何問題。

(Operator Instructions). And I'm showing no questions in the queue?We do have a question now, andthat is from the line of Stephen Willey with Stifel Nicolaus.

（操作員說明）。我在隊列中沒有顯示任何問題？我們現在確實有一個問題，來自 Stephen Willey 和 Stifel Nicolaus 的提問。

Hi, guys. Thanks for taking my question. Scott, I was just wondering how you are kind of thinking about Zytiga being moved up to front line, and then I guess specifically what looks like the eventual approval of 3100 in the refractory setting? And do you get the idea that those patients who see one agent in front line will be precluded from seeing the other in the refractory setting, or do you also get the idea that those patients that see Zytiga at the front line may also be precluded from seeing Zytiga refractory?

嗨，大家好。感謝您提出我的問題。 Scott，我只是想知道您對 Zytiga 被調到前線有何看法，然後我猜想在難治性環境中最終批准 3100 會是什麼樣子？您是否認為那些在前線看到一種藥物的患者將被排除在難治性環境中看到另一種藥物，或者您是否也認為那些在前線看到Zytiga 的患者也可能被排除在難治性環境中看到 Zytiga 難治嗎？

Maybe we'll kind of speak to the landscape piece. As you well know from our discussions, the landscape, particularly in the area of the post-chemo, has been -- a lot of people have been trying to figure out what the landscape looks like with respect to sequencing which players are in that space specifically. And I think whatwe have seen this morning with [Zytiga's] announcement is suggesting that migration that we have been anticipating for some time may in fact be ready to occur in the not too distant future.

也許我們會談談風景片。正如您從我們的討論中所知道的那樣，情況，特別是在化療後的領域，很多人一直在試圖弄清楚根據哪些玩家在該空間進行排序的情況。具體來說。我認為我們今天早上看到的 [Zytiga 的] 公告表明，我們已經期待了一段時間的遷移實際上可能已經準備好在不遠的將來發生。

So I think what that does is it starts to move the crowding, I guess if you will, away from the chemo space and into the pre-chemo space. That is an excellent position for patients obviously, as we get more opportunities for treating these individuals. With respect to our development plan I think it is very good, because it -- maybe we'll speak to a little bit of the patient population.

所以我認為這會開始將人群從化療空間轉移到化療前空間，我想如果你願意的話。顯然，這對患者來說是一個極好的位置，因為我們有更多的機會來治療這些人。關於我們的發展計劃，我認為這是非常好的，因為它——也許我們會與一小部分患者群體交談。

If you think about the pre-chemo patients, they typically are asymptomatic, and so if they are going to be treating with anti-androgen directed pathway drugs, when they progress they're likely be progressing with symptomatic disease, and historically chemotherapy has been utilized in the population. So as the new agents migrate to the front end, I think that puts more importance on the utilization of chemotherapy, which is where we obviously have our development plan. And with the migration, there will be very few other agents. As we said in the prepared script, there's I think just going be a real important need for an agent like custirsen to improve on the chemotherapies as these other agents migrate to the pre-chemo space.

如果您考慮化療前的患者，他們通常是無症狀的，因此，如果他們要使用抗雄激素定向途徑藥物進行治療，當他們病情進展時，他們很可能會出現有症狀的疾病，並且歷史上化療一直是在人群中使用。因此，隨著新藥物遷移到前端，我認為化療的利用變得更加重要，這顯然是我們的發展計劃。而且隨著遷移，其他代理將會很少。正如我們在準備好的腳本中所說，我認為隨著其他藥物遷移到化療前空間，像 custirsen 這樣的藥物將真正需要改進化療。

As far as sequencing, there is not enough data yet, Steve, I don't think with respect to abiraterone followed by abiraterone or [abi versus NDV] in the sequencing, or reverse that scenario. There's been lots of data presented at the ASCO GU conference in the translational session talking about cross talk of potential resistance, but I think there has to be sequencing studies to evaluate. It's probably more -- is a scenario where patients get treated with the abiraterone in the pre-chemo wouldn't see it in the post setting. I think you'd probably switch to different agent if -- particularly if they are treated to progression, which is the new paradigm that's being utilized. Other than that it would be hard to speculate.

至於測序，還沒有足夠的數據，史蒂夫，我不認為在測序中先使用阿比特龍，然後使用阿比特龍或[abi vs NDV]，或者逆轉這種情況。 ASCO GU 會議的轉化會議上提出了很多數據，討論潛在耐藥性的串擾，但我認為必須進行測序研究來評估。更可能的是，患者在化療前接受阿比特龍治療，但在化療後卻看不到這種情況。我認為你可能會切換到不同的代理，如果 - 特別是如果他們接受進展，這是正在利用的新範例。除此之外，很難推測。

In terms of you moving forward with Zytiga at this point, I know that you had previous shown in a translational session -- I believe at ASCO last year -- some synergy on the preclinical front with custirsen and 3100. So I'm just wondering if you moving forward with Zytiga would preclude you from potentially doing anything on the 3100 front, or are you guys just pretty much agnostic?

就您目前與 Zytiga 的進展而言，我知道您之前曾在翻譯會議上展示過（我相信去年在 ASCO 上）與 custirsen 和 3100 在臨床前方面的一些協同作用。所以我只是想知道如果您繼續使用Zytiga 會妨礙您在3100 方面做任何事情，或者你們只是非常不可知論？

Yes, we're -- obviously, 427 is a proprietary asset of ours, where are that is now partnered, and so we have the freedom to move into the space that we feel is biologically appropriate for the agent, which is we went forward immediately with the Zytiga as announced at ASCO GU.

是的，顯然，427 是我們的專有資產，現在在哪里合作，因此我們可以自由地進入我們認為在生物學上適合特工的空間，這就是我們前進的方向正如在ASCO GU 上宣布的那樣，立即使用Zytiga。

With respect to custirsen, you are right. We have presented data last year at a couple of conferences and again a couple of weeks ago at EAU, where chronic exposure of MDV3100 preclinically has enough regulation event to cluster, and you knock out cluster and improve activity of MDV. So there is synergy that has been generated in that regard.

關於custirsen，你是對的。我們去年在幾次會議上以及幾週前在 EAU 上提供了數據，其中 MDV3100 的長期暴露在臨床前有足夠的調節事件來聚集，並且您可以消除聚集並提高 MDV 的活性。因此，在這方面已經產生了協同作用。

The decision to move into clinical development, though, is one that has to be taken by Teva. They are obviously licensee of this agent, and as Michelle was articulating in the prepared statements, that cost would translate over to Teva, so they have the ultimate call in making the decision to go forward. Clearly there is biologic rationale that has been presented.

不過，進入臨床開發的決定是 Teva 必須做出的。他們顯然是該代理商的被許可人，正如米歇爾在準備好的聲明中所闡明的那樣，這筆費用將轉化為梯瓦製藥，因此他們擁有做出繼續決定的最終決定權。顯然，已經提出了生物學原理。

Two quick more questions, if I may. One, can you confirm that the [cenopy] trial is actually a superiority study, Jevtana versus docetaxel in front line?

如果可以的話，還有兩個問題。第一，您能否確認 [cenopy] 試驗實際上是一項優效性研究，Jevtana 與多西他賽在前線的比較？

Cindy, do you know if that is specifically a superiority trial?

辛迪，你知道這是否是專門的優勢試驗嗎？

No, I don't know if I feel that I can comment on that.

不，我不知道我是否覺得我可以對此發表評論。

There is certainly a trial, Steve, and other participants may not be aware of this, where there is a direct comparison of cabazitaxel to docetaxel, and that is in the front line setting. And that is one of the other reasons that we really embrace the concept of doing this study in the second line with cabazitaxel, because if cabazitaxel does take over for docetaxel in the front line, clearly we want to protect the franchise with our development plan. So I think the second line survival trial that we've embraced for cabazitaxel is strategically important.

當然有一項試驗，史蒂夫，其他參與者可能沒有意識到這一點，其中有卡巴他賽與多西他賽的直接比較，而且是在前線環境中進行的。這是我們真正接受在卡巴他賽二線進行這項研究的概念的其他原因之一，因為如果卡巴他賽確實取代了多西他賽在一線，顯然我們希望通過我們的開發計劃來保護特許經營權。因此，我認為我們對卡巴他賽進行的二線生存試驗具有戰略意義。

And then just lastly, should we expect to see anything at ASCO at all?

最後，我們應該期待在 ASCO 上看到什麼嗎？

ASCO AGM?

阿斯科年度股東大會？

Yes, the general meeting in June.

是的，六月的股東大會。

Yes, we will have to wait for abstracts and so on to go forward before we can comment on any presentations for ASCO.

是的，我們必須等待摘要等才能繼續，然後才能對 ASCO 的任何演示發表評論。

Just one, we just did look up on the cabazitaxel study, and it is in fact superiority.

只有一件事，我們剛剛查了一下卡巴他賽的研究，它實際上是優越性的。

Okay. Thank you very much, andcongrats on the progress.

好的。非常感謝，並祝賀取得的進展。

Thanks a lot, Steve.

非常感謝，史蒂夫。

Our next question comes from the line of Katherine Xu with William Blair.

我們的下一個問題來自凱瑟琳·徐和威廉·布萊爾的對話。

Good afternoon. Sorry, I jumped on the call a little bit late. I apologize if you have already commented on this. Just wondering for the increasing in size of SYNERGY, can you comment on the rationale and also speak about assumptions?

下午好。抱歉，我接電話有點晚了。如果您已經對此發表評論，我深表歉意。只是想知道 SYNERGY 規模的增加，您能評論一下其基本原理並談談假設嗎？

Sure. Cindy, do you want to go ahead and answer Katherine's question.

當然。辛迪，你想繼續回答凱瑟琳的問題嗎？

Right, it was two-fold. Obviously, as you saw, changing the hazard ratio from 0.72 to 0.75, thatalso was based on the increase of 200 patients, as well as increasing a safety profile that would be needed for an application with SYNERGY alone. FDA usually likes to have a minimum of 600 if not more patients, and that allows then 500 of the 1,000 patients to be treated with custirsen and docetaxel and that would be added to Phase 2 about the exact same amount of custirsen and docetaxel of a little over 100 patients. So it is really allowing both benefit and risk analysis.

是的，它是兩倍。顯然，正如您所看到的，將風險比從 0.72 更改為 0.75，這也是基於 200 名患者的增加，以及單獨使用 SYNERGY 的應用所需的安全性的提高。 FDA 通常希望有至少600 名（如果不是更多）患者，這允許1,000 名患者中的500 名接受custirsen 和多西他賽治療，並且將添加到第2 階段，大約與custirsen 和多西他賽的量完全相同超過100名患者。因此，它確實允許進行收益和風險分析。

Thank you for that. And then one other thing is, one cannot help noticing [how the dendun of exlexus] is showing up wherever OGX-427 is, right? So they are doing Zytiga failure study. They're doing a combination with Zytiga. They're showing up in front line [study], pre-chemo study, in [NCRPC] and also in bladder cancer. So just curious from your perspective, so how are you looking at the mechanisms and what are you thinking about a future positioning?

謝謝你。還有一件事是，無論 OGX-427 出現在哪裡，人們都會情不自禁地註意到 [exlexus 的 dendon] 出現在哪裡，對嗎？所以他們正在進行 Zytiga 失敗研究。他們正在與 Zytiga 進行組合。他們出現在前線[研究]、化療前研究、[NCRPC] 以及膀胱癌中。從您的角度來看，您很好奇，您如何看待這些機制以及您對未來的定位有何看法？

Yes, I guess we should be proud that we are being followed. The biology is very different with respect to the activity of these agents. With 427 specifically, Hsp27 and the target of [their agent] are completely different biologies. There is some intent to do some look at how these things may work together, and I think generally there could be some potential, but those haven't been looked at.

是的，我想我們應該為自己被跟踪而感到自豪。這些藥物的活性在生物學上有很大不同。具體而言，對於 427，Hsp27 和[其製劑]的目標是完全不同的生物製劑。有人打算研究這些東西如何協同工作，我認為一般來說可能有一些潛力，但這些還沒有被研究過。

I don't think there is a direct competitive nature of these. I think we are in a world for both prostate and bladder cancer, specifically where we need more agents to be able to address these patients, and we are in a land today of having to use combination strategies to achieve the best results. So I think in the future, although we have to independently go down the pathway of independently verifying results, at some point those do come together for combination strategies, usually different than trying to be directly competitive.

我不認為這些之間存在直接競爭性質。我認為我們正處在一個同時存在前列腺癌和膀胱癌的世界，特別是我們需要更多的藥物來治療這些患者，而我們今天正處於一個必須使用聯合策略才能取得最佳結果的時代。所以我認為，在未來，雖然我們必須獨立走獨立驗證結果的道路，但在某些時候，這些確實會結合在一起形成組合策略，通常與試圖直接競爭不同。

Katherine, does that answer your question?

凱瑟琳，這能回答你的問題嗎？

Yes. Thank you.

是的。謝謝。

Thanks, Katherine.

謝謝，凱瑟琳。

Next on the line Philippa Flint with Bloom Burton.

接下來是菲利帕·弗林特和布魯姆·伯頓。

Thanks. Just a couple of quick questions. Operationally, will Teva run this new second line trial?

謝謝。只是幾個簡單的問題。從操作上來說，Teva 會進行這個新的二線試驗嗎？

Cindy, go ahead.

辛迪，繼續吧。

The second line trial will be run by OncoGenex. Obviously Teva is supporting it as far as the financial cost, but we will be primarily running it. But as with both trials, we have always treated it as a collaboration between the two companies, so yes, Teva will be involved in the study.

二線試驗將由 OncoGenex 進行。顯然，梯瓦公司在財務成本方面提供支持，但我們將主要負責運營它。但與這兩項試驗一樣，我們始終將其視為兩家公司之間的合作，因此梯瓦製藥將參與這項研究。

Okay. And will you make any attempt to use the same sites that you already have open for the first line, or what is your strategy in terms of what physicians you will target?

好的。您是否會嘗試使用您已經為第一線開放的相同網站，或者您針對目標醫生的策略是什麼？

Those sites that are interested, yes, we will obviously be happy to have them join, because obviously they already showed a commitment to custirsen's development plan. But also we need to expand, and we are look at expanding into the European countries, so of course, there will be a lot of new sites that will come on to the study.

那些感興趣的網站，是的，我們顯然會很高興讓他們加入，因為顯然他們已經表現出了對 custirsen 發展計劃的承諾。但我們也需要擴展，我們正在考慮擴展到歐洲國家，所以當然，將會有很多新的站點參與這項研究。

Okay. And then finally on closing out the SATURN trial, will the existing patients be allowed to continue, or how do you plan to manage that?

好的。最後，在 SATURN 試驗結束時，現有患者是否可以繼續進行，或者您打算如何處理？

Yes. In fact, what we are doing as of today is just notifying the sites that the study is closed to any further enrollment. All patients that have been -- even signed a consent as of today will continue on the trial, and all patients that are on treatment on the trial will continue per the protocol.

是的。事實上，我們今天所做的只是通知網站該研究已停止接受任何進一步的註冊。截至今天，所有已經簽署同意書的患者都將繼續參加試驗，所有在試驗中接受治療的患者也將繼續按照方案進行。

Okay. Great. Thanks very much.

好的。偉大的。非常感謝。

Thanks, Philippa

謝謝，菲利帕

(Operator Instructions). And next up we have Mike Kig with Rodman and Renshaw.

（操作員說明）。接下來我們有邁克·基格、羅德曼和倫肖。

Thank you, my question was answered earlier.

謝謝，我的問題之前已經回答了。

Thanks, Mike.

謝謝，邁克。

At this time I'm showing no further questions.

此時我沒有再提出任何問題。

Great. In conclusion we have had an exciting start to it 2012. We continue to move forward the development programs for custirsen and OGX-427 in a thoughtful and strategic manner, adapting to the dynamics of a changing landscape and treatment paradigms. We are confident in our path forward and remain committed to our goal of bringing new treatment options to patients in the most timely and efficient manner possible. We are looking forward to completing enrollment of SYNERGY, our primary registration trial in prostate cancer, later this year and to providing future data updates to OGX-427 in clinical programs. Thank you very much for participating.

偉大的。總之，我們在 2012 年有了一個令人興奮的開始。我們繼續以深思熟慮和戰略性的方式推進 custirsen 和 OGX-427 的開發計劃，適應不斷變化的環境和治療範式。我們對前進的道路充滿信心，並繼續致力於以最及時、最有效的方式為患者提供新的治療選擇的目標。我們期待在今年晚些時候完成 SYNERGY（我們在前列腺癌方面的主要註冊試驗）的註冊，並為臨床項目中的 OGX-427 提供未來的數據更新。非常感謝您的參與。

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may disconnect. Have a great day.

女士們、先生們，感謝你們參加今天的會議。程序到此結束。您可以斷開連接。祝你有美好的一天。