Molecular Templates Inc (MTEM) 2006 Q2 法說會逐字稿

Ladies and gentlemen good day and thank you for your patience. We'd like to welcome you to this Threshold Pharmaceuticals second quarter financial results conference call. As a reminder, today's call is being recorded.

女士們、先生們，美好的一天，感謝你們的耐心等待。我們歡迎您參加 Threshold Pharmaceuticals 第二季財務績效電話會議。提醒一下，今天的通話正在錄音。

And now for opening remarks and introductions I'd like to turn the conference over to Ms. Denise Powell; please go ahead.

現在，我想請丹尼斯鮑威爾女士致開幕詞和介紹會議。請繼續。

Good afternoon. I'm Denise Powell, Director of Corporate Communications at Threshold. Thank you for joining us on this conference call. With me are Barry Selick, Chief Executive Officer; Michael Ostrach, Chief Operating Officer; Jan Swearson, Chief Financial Officer; and Alan Colowick, Threshold's Chief Medical Officer.

午安.我是 Denise Powell，Threshold 企業傳播總監。感謝您參加我們這次電話會議。和我在一起的有執行長巴里·塞利克 (Barry Selick)；麥可‧奧斯特拉克，營運長； Jan Swearson，財務長；以及 Threshold 的首席醫療官 Alan Colowick。

Before we begin, I would like to make the following disclaimer. This conference call will include forward-looking statements regarding Threshold's product candidates, clinical trial progress and results, potential therapeutic uses and benefits of our product candidates, and financial results estimates and projections. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.

在我們開始之前，我想做以下免責聲明。本次電話會議將包括有關 Threshold 候選產品、臨床試驗進展和結果、候選產品的潛在治療用途和益處以及財務結果估計和預測的前瞻性陳述。這些陳述涉及風險和不確定性，可能導致實際結果與此類前瞻性陳述中的結果有重大差異。

Potential risks and uncertainties include but are not limited to Threshold's ability to commence, enroll, and complete its anticipated clinical trials and analyze data; issues arising in a regulatory process and the results; the time and expense required to conduct such clinical trials; the results of such clinical trials, including unanticipated product safety issues and efficacy results; the ability to achieve the intended benefits of the expense reductions and refocusing efforts, and the ability to in-license other compounds or programs.

潛在風險和不確定性包括但不限於 Threshold 開始、招募和完成其預期臨床試驗和分析數據的能力；監管過程中出現的問題和結果；進行此類臨床試驗所需的時間和費用；此類臨床試驗的結果，包括意外的產品安全問題和功效結果；實現費用削減和重新集中精力的預期效益的能力，以及獲得其他化合物或項目許可的能力。

Further information regarding these and other risks is included under the heading "Risk Factors" in Threshold's quarterly report on Form 10-Q, which was filed with the Securities and Exchange Commission on May 15, 2006, and is available from SEC's website and on our website under the heading "Investors." We undertake no duty to update any forward-looking statement made in this conference call.

有關這些風險和其他風險的更多資訊包含在Threshold 的10-Q 季度報告的「風險因素」標題下，該報告於2006 年5 月15 日向美國證券交易委員會提交，可從SEC 網站和我們的網站取得。網站標題為「投資者」。我們不承擔更新本次電話會議中所做的任何前瞻性聲明的責任。

I will now turn the call over to Barry.

我現在將把電話轉給巴里。

Good afternoon everybody, and thank you for joining us. I'll make some remarks about the second quarter financial results and then I'll explain how recent results have affected our strategy moving forward.

大家下午好，感謝您加入我們。我將對第二季的財務表現發表一些評論，然後我將解釋最近的業績如何影響我們前進的策略。

As we announced last month, we have discontinued the TH070BPH program, and furthermore we have discontinued all efforts relating to analogs of TH-070 for the potential treatment of BPH.

正如我們上個月宣布的那樣，我們已經停止了 TH070BPH 項目，此外，我們還停止了與 TH-070 類似物有關的潛在治療 BPH 的所有努力。

In spite of terminating this program, however, for the next 2 quarters, we will continue to incur expenses related to this program as all patients are being monitored for 3 months off-drug for safety follow-up.

然而，儘管終止了該計劃，但在接下來的兩個季度，我們將繼續承擔與該計劃相關的費用，因為所有患者都將接受為期 3 個月的停藥監測，以進行安全追蹤。

Additionally, the remainder of the year there will be costs associated with closing down operations at the clinical trial sites, labs, and our contract research organizations. Therefore, due to expenses associated with discontinuing this program, completing our 2 ongoing Gluphosfamide trials and initiating the trials in new Gluphosfamide indications, we expect expenses particularly R&D to increase in the second half of this year.

此外，今年剩餘時間裡，臨床試驗地點、實驗室和合約研究組織的關閉運作也會產生相關費用。因此，由於與終止該計劃、完成我們正在進行的兩項草磷酰胺試驗以及啟動新的草磷酰胺適應症試驗相關的費用，我們預計今年下半年的費用，特別是研發費用將會增加。

In order to reduce our expenses going forward, we announced a reduction in force to employees today. The majority of employees who are affected by this will have their last day at Threshold on August 15. This reduction in force affected every group and virtually every job title in the Company. We sought to retain those core functions that will preserve our ability to continue prosecuting existing programs, while being able to evaluate and respond to new opportunities quickly. We will pay approximately $1.2 million in the second half of 2006 for costs associated with the severances. For 2006 we expect cash views for operations to be between $55 million and $58 million. With the reduction in force and by cutting outside expenses, we expect cash to last at least through the middle of 2008, which should permit the completion of all ongoing Gluphosfamide and 2DG clinical trials, top-line results in Phase II studies for the Gluphosfamide, and at least 2 indications beyond pancreatic cancer, and initiation of clinical development of at least 1 of our own discovery programs.

為了減少未來的開支，我們今天宣布減少員工人數。大多數受此影響的員工將於 8 月 15 日在 Threshold 工作的最後一天。這次裁員影響了公司的每個團隊和幾乎每個職位。我們力求保留這些核心職能，以維持我們繼續執行現有計畫的能力，同時能夠快速評估和應對新的機會。我們將在 2006 年下半年支付約 120 萬美元的遣散費。 2006 年，我們預計營運現金額將在 5,500 萬美元至 5,800 萬美元之間。隨著人力的減少和外部開支的削減，我們預計現金至少能持續到 2008 年中期，這將允許完成所有正在進行的 Gluphosfamide 和 2DG 臨床試驗、Gluphosfamide 的 II 期研究的主要結果、以及至少2 個胰腺癌症以外的適應症，並啟動至少1 個我們自己的發現項目的臨床開發。

To that end, we plan to start additional Phase II trials of Gluphosfamide and all or a sub-set of an ovarian cancer, sarcoma, and small-cell lung cancer by the end of this year.

為此，我們計劃在今年年底前啟動 Gluphosfamide 以及所有或部分卵巢癌、肉瘤和小細胞肺癌的 II 期試驗。

We will continue to prosecute the ongoing 2Deoxyglucose program in solid tumors alone, and in combination with Taxotere and we have seen some encouraging examples of stable disease and our investigators remain enthusiastic about its promise.

我們將繼續推進正在進行的單獨治療實體瘤的 2Deoxyglucose 項目，以及與泰索帝聯合治療的項目，我們已經看到了一些穩定疾病的令人鼓舞的例子，我們的研究人員仍然對其承諾充滿熱情。

Now let me turn your attention to development that is quite exciting for the Company. As you are aware, we have built a robust discovery research capability at Threshold under the leadership of Dr. Mark Matteucci. Our focus has been to develop a sustainable pipeline of clinical development candidates that target the unique metabolic properties in solid tumors. Recently, we nominated our first IND candidate, TH-302 from these internal discovery efforts.

現在讓我把你們的注意力轉向對公司來說非常令人興奮的發展。如你所知，在 Mark Matteucci 博士的領導下，我們在 Threshold 建立了強大的發現研究能力。我們的重點是開發針對實體瘤獨特代謝特性的可持續臨床開發候選產品。最近，我們從這些內部發現工作中提名了我們的第一個 IND 候選藥物 TH-302。

This is a significant milestone for Threshold. TH-302 is a hypoxically-activated pro-drug or half; halfs are designed such that under the oxygen concentrations found in normal, healthy tissues, they're relatively benign. However, in tissues of extremely low oxygen concentration that exists within poorly vascularized hypoxic solid tumors, the pro-drug is activated to release a toxin, which targets the hypoxic and surrounding tumor tissues. It is believed that a half, either as a single agent or in combination with traditional cancer therapy that targets rapidly-dividing tissues should permit the treatment of not only those portions of the tumor that typically respond to existing therapy, but also those tumor cells that evade that same therapy and ultimately give rise to relapse.

對 Threshold 來說，這是一個重要的里程碑。 TH-302 是一種低氧活化的前藥或半藥；一半的設計使得在正常健康組織中的氧氣濃度下，它們相對良性。然而，在血管化不良的缺氧實體瘤內存在的氧濃度極低的組織中，前藥被激活以釋放毒素，該毒素針對缺氧組織和周圍腫瘤組織。據信，一半藥物，無論是作為單一藥物，還是與針對快速分裂組織的傳統癌症治療相結合，不僅可以治療通常對現有治療有反應的腫瘤部分，還可以治療那些對現有治療有反應的腫瘤細胞。逃避同樣的治療並最終導致復發。

Importantly, all solid tumors possess varying degrees of hypoxia, which is correlated with a poor prognosis.

重要的是，所有實體瘤都具有不同程度的缺氧，這與不良預後有關。

TH-302 appears to be highly selective for hypoxic versus normoxic, or normal oxygen conditions. We've generated very promising results in 2 different xenograft models of pancreatic cancer. In one of those models, a so-called orthotopic xenograft model that we believe closely reflects the state of a natural pancreatic tumor, Gluphosfamide in combination with Gencitabine yielded cures. That is complete disappearance of the primary and metastatic lesions in half of the animals that we studied. We have observed similar responses in a prostate cancer xenograft model in combination with Taxotere.

TH-302 似乎對缺氧條件與常氧條件或正常氧條件具有高度選擇性。我們在兩種不同的胰臟癌異種移植模型中取得了非常有希望的結果。在其中一個模型中，即所謂的原位異種移植模型，我們認為該模型密切反映了天然胰腺腫瘤的狀態，葡磷酰胺與根西他濱聯合治療產生了治癒效果。我們研究的一半動物的原發性和轉移性病變完全消失。我們在聯合泰索帝的前列腺癌移植模型中觀察到類似的反應。

The Company has nominated this lead compound as its next clinical candidate, and assuming that pre-clinical and manufacturing programs proceed as anticipated, we plan to file an IND Application by the middle of 2007.

本公司已提名該先導化合物作為其下一個臨床候選藥物，並假設臨床前和生產計劃按預期進行，我們計劃在 2007 年中期提交 IND 申請。

Additionally, we will continue to evaluate late-stage discovery and clinical stage product candidates for possible acquisition on in-license that may benefit from our expertise in drug discovery and development at Threshold.

此外，我們將繼續評估後期發現和臨床階段的候選產品，以便可能獲得許可，這可能會受益於我們在 Threshold 的藥物發現和開發方面的專業知識。

Finally, the past 3 months have been challenging for Threshold as well as our shareholders. The failure of TH-070 was a disappointment for all of us, although it has not shaken our confidence I our other programs and passion to discover and develop successful drugs. I remain absolutely committed to Threshold; we have a strong team that is intensely focused on prosecuting our existing research and development programs, and finding new opportunities that together we believe will build shareholder value.

最後，過去 3 個月對 Threshold 以及我們的股東來說都是充滿挑戰的。 TH-070 的失敗讓我們所有人都感到失望，儘管它並沒有動搖我們對其他項目的信心以及發現和開發成功藥物的熱情。我仍然絕對致力於 Threshold；我們擁有一支強大的團隊，專注於執行我們現有的研發計劃，並尋找新的機會，我們相信這些機會將共同創造股東價值。

With that, we'll be happy to take your questions.

這樣，我們將很樂意回答您的問題。

+++ q-and-a

+++ 問答

Thank you. [OPERATOR INSTRUCTIONS].

謝謝。 [操作員說明]。

We have no questions in our queue at this time, But once again if you would like to ask a question [OPERATOR INSTRUCTIONS].

目前我們的隊列中沒有任何問題，但如果您想再次提問[操作員說明]。

Franklin Berger, FMB Research.

富蘭克林伯傑，FMB 研究。

Good afternoon Barry; could you give us a little more insight as to the pre-clinical work in this new compound that you'll be taking forward, and the animals studies that lead you to feel very encouraged about its potential?

下午好，巴里；您能否向我們介紹一下您將要推進的這種新化合物的臨床前工作，以及讓您對其潛力感到非常鼓舞的動物研究？

We would be happy to Franklin; let me turn it over to Alan for that.

我們很高興富蘭克林；讓我把它交給艾倫吧。

Hi Franklin; yeah, we're really excited about this. This is the lead of a number of compounds that we've been working on here for the last couple of years which are, which we call hypoxically-activated pro-drugs, and the basic concept is to take molecules, which are toxins, that is that are toxic, that coupling them with a blocker molecule, basically that makes the toxin inert under normal oxygen concentrations, but under areas of extreme hypoxy which, of course, all [inaudible] tumors have, and for that matter even some Hematologic malignancies.

嗨，富蘭克林；是的，我們對此感到非常興奮。這是我們過去幾年一直在這裡研究的許多化合物的先導，我們稱之為缺氧激活前藥，基本概念是採取分子，即毒素，是有毒的，將它們與阻斷劑分子結合，基本上使毒素在正常氧氣濃度下呈惰性，但在極度缺氧的區域下，當然，所有[聽不清楚]腫瘤都有這種情況，就這一點而言，甚至是一些血液惡性腫瘤。

Under extreme hypoxia, this blocker compound is essentially removed from the molecule exposing the toxins which we think is very important, not only in terms of a therapeutic index; that is that we'll absolutely serve as a targeting mechanism for the tumor itself, but we believe and I think the emerging field in cancer stem-cell biology, we believe that this is where most of the really bad actors live in cancer cells, and so we think we're going to have a profound impact with these classes of agents, either as a single agent or potentially in combination with other agents.

在極度缺氧的情況下，這種阻斷劑化合物基本上從暴露毒素的分子中去除，我們認為這不僅在治療指數方面非常重要，而且在治療指數方面也非常重要。也就是說，我們絕對會作為腫瘤本身的靶向機制，但我們相信，而且我認為癌症幹細胞生物學的新興領域，我們相信這是大多數真正壞演員生活在癌細胞中的地方，因此，我們認為我們將對這些類別的代理產生深遠的影響，無論是作為單一代理還是可能與其他代理結合。

We've got some very interesting results that I think Barry detailed, and now 2 very separate diseases, pancreatic cancer and prostate cancer. We'll continue to investigate other tumor types with this lead compound as we progress it towards an IND, but in addition we have an active discovery in clinical program for a number of these types of molecules that are showing promise.

我們得到了一些非常有趣的結果，我認為巴里詳細介紹了這些結果，現在有兩種非常不同的疾病，胰腺癌和前列腺癌。隨著我們將其推向 IND，我們將繼續用這種先導化合物研究其他腫瘤類型，但此外，我們在臨床計劃中積極發現了許多顯示出前景的此類分子。

Are you able to tell us what toxins you've been using for these particular endeavors?

您能告訴我們您在這些特定的努力中使用了哪些毒素嗎？

We're not prepared to do that at this time Franklin, but I think you can rest assured that as time goes on and we begin to discuss thee more publicly we'll certainly be sharing that.

富蘭克林，我們現在不准備這樣做，但我想你可以放心，隨著時間的推移，我們開始更公開地討論你，我們肯定會分享這一點。

Thank you very much.

非常感謝。

Franklin we are well aware of a company in the Pacific Northwest that is very skilled in the development and use of these toxins.

富蘭克林，我們很清楚太平洋西北地區的一家公司在開發和使用這些毒素方面非常熟練。

Thank you.

謝謝。

[OPERATOR INSTURCTIONS].

[操作員說明]。

Michael Dinerman, CIBC.

邁克爾·迪納曼，CIBC。

Hi there, yes; I was wondering about 2DG and what kind of tumor models you're planning on moving forward in and what pre-clinical data has shown.

你好，是的；我想知道 2DG 以及您計劃推進哪種腫瘤模型以及臨床前數據顯示了什麼。

Again, let me ask Alan to address that.

讓我再次請艾倫解決這個問題。

Yes Michael, we are currently in the clinic with 2DG in a Phase I study where it's being administered alone and in combination with Taxotere in patients with a variety of solid tumors. The purpose of that study, of course, is safety and to determine maximum tolerated dose of 2Deoxyglucose administered in a daily fashion.

是的，邁克爾，我們目前正在臨床上進行 2DG 的 I 期研究，該研究將單獨給藥或與泰索帝聯合給藥，用於治療多種實體瘤患者。當然，研究的目的是安全性並確定每日施用 2 脫氧葡萄糖的最大耐受劑量。

In addition, however, we've seen some I think fairly interesting responses in terms of stable disease at some of the lower doses as we progress through the dose escalation, and when that study is completed, obviously if there's a signal that emerges from this Phase I study that would inform additional Phase II studies, we'll certainly take that into account. Pre-clinically, we've observed activity of 2DB particularly in combination with other agents and most notably other cyto-toxic agents. We've seen synergistic results across a wide range of tumor types; breast cancer, lung cancer, sarcoma, ovarian, and we'll also use that obviously to help us guide the future clinical development.

然而，此外，隨著我們劑量遞增的進展，我們已經看到一些我認為在某些較低劑量的穩定疾病方面相當有趣的反應，當該研究完成時，顯然如果有一個信號從中出現第一階段研究將為其他第二階段研究提供資訊，我們當然會考慮到這一點。在臨床前，我們觀察到 2DB 的活性，特別是與其他藥物（尤其是其他細胞毒性藥物）合併使用時的活性。我們已經看到了多種腫瘤類型的協同結果；乳癌、肺癌、肉瘤、卵巢癌，我們顯然也會用它來幫助我們引導未來的臨床發展。

Okay thank you.

好的謝謝。

And at this point, we have no further questions in our queue. I'd like to turn the conference back over to our presenters for additional or closing remarks.

此時，我們的隊列中沒有其他問題了。我想將會議轉回給我們的主持人進行補充或結束語。

Okay, once again thank you all very much for participating in the call, and as always, we appreciate your interest in Threshold. Thanks.

好的，再次非常感謝大家參與此電話會議，並且一如既往，我們感謝您對 Threshold 的興趣。謝謝。

And that does conclude today's conference call. Thank you for your participation and have a great day.

今天的電話會議到此結束。感謝您的參與，祝您有美好的一天。