GT Biopharma Inc (GTBP) 2021 Q2 法說會逐字稿

Greetings, and welcome to the GT Biopharma second-quarter 2021 conference call. (Operator Instructions) At this time, I'd like to turn the conference call over to David Castaneda, Investor Relations for the company. Thank you. You may proceed.

您好，歡迎參加 GT Biopharma 2021 年第二季度電話會議。 （操作員指示）此時，我想將電話會議轉給公司投資者關係部的 David Castaneda。謝謝。您可以繼續。

Thank you, operator. Good morning, everyone, and welcome to GT Biopharma second-quarter 2021 conference call. Earlier this morning, we issued a press release summarizing the company's second-quarter 2021 corporate updates that management will discuss on the call today. You can access the press release by going to the News & Media section and then the press releases page on our website at gtbiopharma.com.

謝謝你，接線員。大家早上好，歡迎參加 GT Biopharma 2021 年第二季度電話會議。今天上午早些時候，我們發布了一份新聞稿，總結了該公司 2021 年第二季度的公司更新，管理層將在今天的電話會議上討論這些更新。您可以通過轉至我們網站 gtbiopharma.com 上的新聞與媒體部分和新聞稿頁面來獲取新聞稿。

GT Biopharma's following presentation and ensuing question-and-answer session will include statements that are or may be deemed forward-looking statements. In some cases, you can identify forward-looking statements by terminology, including, anticipates, believes, can, continue, could, estimates, expects, intends, may, plans, potential, predicts, should, will, would or the negative thereof, other variations thereon or other comparable terminology.

GT Biopharma 的以下演示和隨後的問答環節將包括屬於或可能被視為前瞻性陳述的陳述。在某些情況下，您可以通過術語來識別前瞻性陳述，包括預期、相信、能夠、繼續、能夠、估計、期望、打算、可能、計劃、潛力、預測、應該、將、將或其否定形式，其上的其他變體或其他類似術語。

We operate in very competitive and rapidly changing environment and new risks emerge from time to time. As a result, it is not possible for management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements we may make.

我們在競爭激烈且瞬息萬變的環境中運營，新的風險不時出現。因此，管理層不可能預測所有風險，我們也無法評估所有因素對我們業務的影響，或者任何因素或因素組合可能導致實際結果與任何結果中包含的結果存在重大差異的程度。我們可能做出的前瞻性陳述。

In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You are cautioned not to place undue reliance upon such forward-looking statements as predictions of future events.

鑑於這些風險、不確定性和假設，本演示文稿中討論的前瞻性事件和情況可能不會發生，實際結果可能與前瞻性陳述中預期或暗示的結果存在重大和不利的差異。請您注意不要過分依賴此類前瞻性陳述，例如對未來事件的預測。

Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. We direct you to our annual report on Form 10-K for the year ended December 31, 2020; our subsequent current reports on Form 8-K; our quarterly report on Form 10-Q for the quarter ended March 31, 2021; and our other filings with the Securities and Exchange Commission.

儘管我們認為前瞻性陳述中反映的預期是合理的，但我們不能保證前瞻性陳述中反映的未來結果、活動水平、業績或事件和情況將會實現或發生。我們將引導您查看截至 2020 年 12 月 31 日的年度 10-K 表格年度報告；我們後續的 8-K 表當前報告；我們截至 2021 年 3 月 31 日的季度 10-Q 表格季度報告；以及我們向美國證券交易委員會提交的其他文件。

Any forward-looking statement included in this presentation speaks only as of the date hereof. Except as required by law, we do not undertake any obligation to update or revise or to publicly announce any update or revision to any of the forward-looking statements, whether as a result of new information, future events or any other reason after the date of this presentation.

本演示文稿中包含的任何前瞻性陳述僅代表截至本報告發布之日的情況。除法律要求外，我們不承擔更新或修訂或公開宣布對任何前瞻性陳述的任何更新或修訂的義務，無論是由於新信息、未來事件或該日期之後的任何其他原因。本次演講的內容。

For all forward-looking statements, we claim the protection of the Safe Harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Nothing in this presentation or discussion shall be deemed an offer to purchase or sell the company's securities.

對於所有前瞻性陳述，我們聲稱受到1995 年《私人證券訴訟改革法案》中包含的前瞻性陳述安全港的保護。本演示或討論中的任何內容均不應被視為購買或出售公司證券的要約。

Now I'd like to turn the call over to Tony Cataldo, Chairman, CEO of GT Biopharma. Tony?

現在我想把電話轉給 GT Biopharma 董事長兼首席執行官 Tony Cataldo。托尼？

Yeah. Thank you, David. Good morning, everyone, and thank you for joining us. As this is GT Biopharma's first scheduled conference call, I want to thank the investment community for paying attention to the progress that GT Biopharma has demonstrated in the first half of this year. Additionally, I want to thank my entire staff for their due diligence, hard work and the contribution they have made for an amazing first half of the year.

是的。謝謝你，大衛。大家早上好，感謝您加入我們。由於這是 GT Biopharma 首次預定的電話會議，我要感謝投資界對 GT Biopharma 在今年上半年所展示的進展的關注。此外，我還要感謝我的全體員工的盡職調查、辛勤工作以及他們為上半年的出色表現所做出的貢獻。

The last fiscal quarter has been marked with numerous events and milestones, reflecting tremendous success for the company. We were added into the Russell 2000, the Chicago Options Exchange, and now have enough money to execute the company's business plans for the next couple of our years, approximately $40 million.

上一個財政季度發生了許多事件和里程碑，反映出公司取得了巨大的成功。我們被納入羅素 2000 指數（芝加哥期權交易所），現在有足夠的資金來執行公司未來幾年的業務計劃，大約為 4000 萬美元。

We also completed our new sponsored research agreement with the University of Minnesota, headed by the TriKE creator, Dr. Jeffrey Miller and his team at the University of Minnesota. This will further enhance our advancement of the TriKE platform, adding more value to GT's expanding portfolio. Our GTB-3550 TriKE clinical trial continues to show safety and clinical results and remains well tolerated with patients who have for all intents and purpose has been written off.

我們還與明尼蘇達大學完成了新的讚助研究協議，該協議由 TriKE 的創建者 Jeffrey Miller 博士及其在明尼蘇達大學的團隊領導。這將進一步增強我們 TriKE 平台的進步，為 GT 不斷擴大的產品組合增加更多價值。我們的 GTB-3550 TriKE 臨床試驗繼續顯示安全性和臨床結果，並且對於所有意圖和目的已被註銷的患者來說仍然具有良好的耐受性。

The TriKE clinical data has shown that it is remarkably effective at activating patient's own NK cells creating persistence of NK cells, proliferation of NK cells, and making NK cells serial killers of cancer cells. Unlike our competitors, we don't need ex vivo outside manufacturing of NK cells or a combination drug therapies to supplement our product. Everything that TriKE does is inside the body.

TriKE臨床數據表明，它在激活患者自身的NK細胞方面非常有效，創造NK細胞的持久性、NK細胞的增殖性，並使NK細胞成為癌細胞的連環殺手。與我們的競爭對手不同，我們不需要體外製造 NK 細胞或聯合藥物療法來補充我們的產品。 TriKE 所做的一切都在體內進行。

The TriKE stands alone in the field of NK cell technology companies as a true monotherapy. Additionally, the TriKE is a toolkit for other NK cell therapies. We had data that shows that. GT will continue to update the investment community as events unfold as well as significant corporate development milestones. I often indicate to existing and prospective investors and analysts that I believe that it is the data and not the CEO that speaks most meaningfully to the merit and potential of GT Biopharma.

TriKE 作為真正的單一療法在 NK 細胞技術公司領域獨樹一幟。此外，TriKE 是其他 NK 細胞療法的工具包。我們的數據表明了這一點。隨著事件的展開以及重要的企業發展里程碑，GT 將繼續向投資界通報最新情況。我經常向現有和潛在的投資者和分析師表示，我相信數據而不是首席執行官最能說明 GT Biopharma 的優點和潛力。

As such, I will now turn the call over to Martin Schroeder, our Chief Technology Officer; and Dr. Greg Berk, our Chief Medical Officer, who will recap the impressive and encouraging data we observed and reported in recent months. We will close out the call with the Q&A session. To reiterate, I'm exceedingly pleased with our advancement over the last quarter as clearly evidenced by our concurrent share price appreciation.

因此，我現在將把電話轉給我們的首席技術官 Martin Schroeder；我們的首席醫療官 Greg Berk 博士將回顧我們近幾個月觀察和報告的令人印象深刻且令人鼓舞的數據。我們將以問答環節結束電話會議。重申一下，我對我們上個季度的進步感到非常滿意，我們同時股價的上漲就清楚地證明了這一點。

And with that, I'll gladly pass this call over to Martin Schroeder. Martin, take it away.

這樣，我很樂意將這個電話轉給馬丁·施羅德。馬丁，把它拿走。

Thank you, Tony. Hello, everyone. As an introduction for those who may be unfamiliar, GT Biopharma's core technology is centered around our proprietary TriKE platform. And this platform originates from the pioneering work of Dr. Jeffrey Miller at the University of Minnesota.

謝謝你，托尼。大家好。為那些可能不熟悉的人介紹一下，GT Biopharma 的核心技術以我們專有的 TriKE 平台為中心。而這個平台源於明尼蘇達大學杰弗裡·米勒博士的開創性工作。

TriKE is designed to harness and enhance the cancer-killing abilities of the patient's endogenous or own natural killer cells, without the need for the addition of supplemental NK cell therapy. TriKE is administered to the patient by infusion. And once bound to the patient's NK cells, TriKE directs the NK cell to target certain tumor-specific proteins or tumor antigens that are expressed, present on the surface of cancer cells, leading to the death of the cancer cell. Notably, and distinct to try to relative to other therapies, TriKE-activated NK cells target and kill multiple cancer cells in a very powerful and serial fashion.

TriKE 旨在利用和增強患者內源性或自身自然殺傷細胞的抗癌能力，無需額外補充 NK 細胞療法。 TriKE 通過輸注給予患者。一旦與患者的 NK 細胞結合，TriKE 就會引導 NK 細胞靶向癌細胞表面表達的某些腫瘤特異性蛋白質或腫瘤抗原，從而導致癌細胞死亡。值得注意的是，與其他療法不同的是，TriKE 激活的 NK 細胞以非常強大和連續的方式靶向並殺死多個癌細胞。

So what is TriKE? TriKE is made up of -- what we call or refer to as recombinant fusion proteins. These are proteins that recognize specific antigens, as I mentioned, on the surface of the cancer cell. And as such, we -- they can be designed and engineered with great flexibility allowing us to target a variety of tumor antigens present on hematologic malignancies, sarcomas, and solid tumors. TriKE, unlike cell therapies, does not require patient-specific customization.

那麼什麼是 TriKE？ TriKE 由我們所說的重組融合蛋白組成。正如我提到的，這些蛋白質可以識別癌細胞表面的特定抗原。因此，我們可以非常靈活地設計和工程化它們，使我們能夠針對血液惡性腫瘤、肉瘤和實體瘤上存在的各種腫瘤抗原。 TriKE 與細胞療法不同，不需要針對患者進行定制。

So, in addition to the compelling clinical data we are seeing with GTB-3550 that's being evaluated in Phase 1 clinical trial, which my colleague Dr. Greg Berk will discuss momentarily, our pipeline consists of several additional TriKE products, which target solid tumor cancers.

因此，除了我們看到的GTB-3550 令人信服的臨床數據（正在1 期臨床試驗中進行評估（我的同事Greg Berk 博士將立即討論）），我們的產品線還包括其他幾種針對實體瘤的TriKE 產品。

Our clinical development pipeline includes TriKE product candidates, which target PD-L1-positive solid tumor cancers, B7-H3-positive solid tumor cancers. There are two positive, solid tumor cancers. And these cancers include lung cancers, breast cancers, ovarian cancers, gastric cancers, and prostate cancers, to name just a few.

我們的臨床開發管道包括 TriKE 產品候選者，其針對 PD-L1 陽性實體瘤癌症、B7-H3 陽性實體瘤癌症。有兩種陽性實體瘤癌症。這些癌症包括肺癌、乳腺癌、卵巢癌、胃癌和前列腺癌等。

The TriKE product candidates are presently undergoing GMP manufacturing and scale up in preparation for filing an investigational drug application with the US FDA for evaluation in humans. We are also working on several additional product -- TriKE product candidates that are in various stages of preclinical evaluation.

TriKE 候選產品目前正在進行 GMP 生產並擴大規模，準備向美國 FDA 提交研究藥物申請以進行人體評估。我們還致力於開發幾種其他產品——處於臨床前評估各個階段的 TriKE 候選產品。

At this point, I'd like to turn the call over to Greg Berk, our Chief Medical Officer friend, and he can proceed to discuss the details of our GTB-3550 clinical program. Greg?

此時，我想將電話轉給我們的首席醫療官朋友 Greg Berk，他可以繼續討論我們的 GTB-3550 臨床計劃的細節。格雷格？

Thanks, Martin. The early preclinical and clinical evidence with our first candidate, TriKE GTB-3550, for the treatment of relapsed/refractory AML and MDS that was reported in the last fiscal quarter is very encouraging. We observe both a positive safety profile and an indication of biologic activity as measured by blast cell reductions.

謝謝，馬丁。上一財季報告的我們的第一個候選藥物 TriKE GTB-3550 用於治療復發/難治性 AML 和 MDS 的早期臨床前和臨床證據非常令人鼓舞。我們觀察到積極的安全性和通過母細胞減少測量的生物活性跡象。

At the 150-microgram dose level, we have one case of Grade 1 CRS, which was not a dose-limiting toxicity. There have been no other clinically significant toxicities observed. And in fact, next week, we are escalating to the next dose level, the 200-microgram cohort.

在 150 微克劑量水平下，我們發現了 1 例 1 級 CRS 病例，這不是劑量限制性毒性。沒有觀察到其他臨床上顯著的毒性。事實上，下週我們將升級到下一個劑量水平，即 200 微克隊列。

To date, 12 patients have been treated in the GTB-3550 Phase 1 trial. Patients 5, 7, 9, and 11 experienced 33%, 61%, 63%, and 50% reduction in the CD33-positive bone marrow blast levels, respectively. 57% of patients treated between 25 and 150 micrograms experienced the reduction in their AML or MDS blast. Activation, proliferation, and persistence of functionally active NK cells occurred without the addition of supplemental NK cells.

迄今為止，GTB-3550 1 期試驗已對 12 名患者進行了治療。 5號、7號、9號和11號患者的CD33陽性骨髓母細胞水平分別下降了33%、61%、63%和50%。在接受 25 至 150 微克劑量治療的患者中，57% 的 AML 或 MDS 原始細胞有所減少。在不添加補充 NK 細胞的情況下，功能活躍的 NK 細胞就會被激活、增殖和持續存在。

NK cell activation has been observed to increase early during treatment and is correlated with a proportional and overall increase of absolute number of NK cells. Targeted delivery of IL-15 to NK cells via the 3550 TriKE showed preferential proliferation of NK cells and significantly less effect on CD8-positive and CD4-positive T cells.

據觀察，NK 細胞活化在治療早期增加，並且與 NK 細胞絕對數量的比例和總體增加相關。通過 3550 TriKE 將 IL-15 靶向遞送至 NK 細胞顯示 NK 細胞優先增殖，並且對 CD8 陽性和 CD4 陽性 T 細胞的影響明顯較小。

We also observed no CD16 shedding by patient's NK cells and saw enhanced HL-60 AML target cell killing ex vivo. This data indicates that GTB-3550 rescues the patient's exhausted and inhibited endogenous NK cells, resulting in their activation, proliferation, and persistence.

我們還觀察到患者的 NK 細胞沒有 CD16 脫落，並且發現 HL-60 AML 靶細胞的離體殺傷能力增強。該數據表明 GTB-3550 拯救了患者耗盡和受抑制的內源 NK 細胞，導致其激活、增殖和持久化。

This early data indicates GTB-3550 therapy demonstrates significant bone marrow level reductions in AML and MDS patients without the need for supplemental autologous and allogeneic stem cells -- I am sorry, cell therapies. This Phase 1 trial is expected to conclude later this fall, and updated safety and efficacy data will be presented in an oral session at the ESMO conference in September.

這一早期數據表明 GTB-3550 療法顯示 AML 和 MDS 患者的骨髓水平顯著降低，而無需補充自體和同種異體幹細胞 - 對不起，細胞療法。該一期試驗預計將於今年秋天晚些時候結束，更新的安全性和有效性數據將在 9 月份的 ESMO 會議的口頭會議上提出。

With that, I'd like to turn the call over to the operator to open up for Q&A. Thank you.

這樣，我想將電話轉給接線員以進行問答。謝謝。

Ladies and gentlemen, at this time we'll begin the question-and-answer session. (Operator Instructions) Justin Walsh, B. Riley Securities.

女士們、先生們，現在我們將開始問答環節。 （操作員指令）Justin Walsh，B. Riley Securities。

Hi. Thanks for taking the questions. I have a couple. Starting off, can you provide any color on what we can expect to see at ESMO? How many patients, how long the follow-up, any details we can get?

你好。感謝您提出問題。我有一對。首先，您能透露一下我們在 ESMO 上可以看到什麼嗎？有多少患者，隨訪多長時間，我們可以獲得任何詳細信息嗎？

Yeah. Greg, you go ahead and answer that. But just to remind everybody, because we are speaking at a major conference, there are certain embargoes that we can't articulate until that conference. All right. Go ahead, Greg.

是的。格雷格，你繼續回答這個問題。但只是提醒大家，因為我們是在一次重要會議上發言，所以在會議之前我們無法闡明某些禁運。好的。繼續吧，格雷格。

Sure. Justin, at ESMO, which is on September 20 or around that time, we will present updated safety data, at least through 12 patients. We're literally dosing patient number 13 next week. So, we most likely won't have data for that patient at ESMO. So, it'll be up through 12 patients.

當然。 Justin，在 9 月 20 日或大約那個時間的 ESMO，我們將至少通過 12 名患者提供最新的安全數據。下週我們將給 13 號患者註射藥物。因此，我們很可能不會在 ESMO 獲得該患者的數據。因此，總共將有 12 名患者。

Got it. And maybe related to that -- so, you'd mentioned that there was the one case of CRS that didn't seem too severe. Can we get any more details on that, like how long after treatment was it observed? How long does it last? What interventions were required and anything else you can give on that front?

知道了。也許與此相關——所以，你提到有一個 CRS 病例看起來不太嚴重。我們能否獲得更多詳細信息，例如治療後觀察了多長時間？持續多久？需要採取哪些干預措施以及您可以在這方面提供哪些其他幫助？

Yes, sure. It's very simple -- it was just fever. So, fever that persists a certain amount of time is -- if it's fever alone without other symptoms, it's a Grade 1 CRS. So, if infection is ruled out, which it wasn't in this case, it's assessed as a possible CRS.

是的，當然。很簡單——只是發燒。因此，發燒持續一定時間，如果只是發燒而沒有其他症狀，則為 1 級 CRS。因此，如果排除了感染（本例中並非如此），則可將其評估為可能的 CRS。

Perfect, thanks. And I'll just have one more before jumping -- yeah.

很好，謝謝。在跳之前我還會再喝一杯——是的。

By the way, Justin, that's not a dose-limiting toxicity of Grade 1 fever CRS.

順便說一句，Justin，這不是 1 級發燒 CRS 的劑量限制性毒性。

Got it. All right. So, I think the last one for me. Maybe just some details on how Dr. Miller's involvement is expected to evolve following the sponsored research agreement, and how that is expected to advance GT's platform.

知道了。好的。所以，我認為最後一個對我來說。也許只是一些關於 Miller 博士的參與在讚助研究協議之後預計將如何發展的細節，以及預計將如何推進 GT 平台的細節。

Yeah. Martin, why don't you take that one? Martin?

是的。馬丁，你為什麼不拿那個呢？馬丁？

Pardon me. My mic was muted. (multiple speakers) Forgive me.

對不起。我的麥克風被靜音了。 （多個發言者）請原諒我。

Yes. So Jeff's involvement with the company will continue to be quite strong. He is one of our founders, and of course, preeminent key opinion leader in the field. The sponsored research agreement, we have several activities planned to help more fully understand TriKE's capabilities, as well as TriKE's influence on NK cell biology during the course of therapy.

是的。因此，傑夫對公司的參與將繼續相當強烈。他是我們的創始人之一，當然也是該領域傑出的關鍵意見領袖。根據贊助的研究協議，我們計劃開展多項活動，以幫助更全面地了解 TriKE 的功能，以及 TriKE 在治療過程中對 NK 細胞生物學的影響。

And as you're, I'm sure, aware, as I mentioned, we are in the -- we are developing several new TriKE product candidates. Some of those are quite interesting dual-targeting TriKEs that simultaneously target two different tumor antigens. The goal, to help better cut off immune escape, particularly when moving into the solid tumor setting. So yes, so Jeff's efforts with the company will continue to be strong and he will be quite actively engaged for the long term.

正如您所言，我確信，正如我所提到的，我們正在開發幾種新的 TriKE 產品候選者。其中一些是非常有趣的雙靶向 TriKE，它們同時靶向兩種不同的腫瘤抗原。目標是幫助更好地切斷免疫逃逸，特別是在進入實體瘤環境時。所以，是的，傑夫在公司的努力將繼續強勁，並且他將長期積極參與。

Got it. Thanks for taking the questions. I'll jump back to the queue.

知道了。感謝您提出問題。我會跳回隊列。

Ram Selvaraju, H.C. Wainwright.

拉姆·塞爾瓦拉朱 (Ram Selvaraju)，H.C.溫賴特。

Thanks very much for taking my questions. Firstly, I was wondering if you could give us some color on the timing of release of final topline data from the 3550 trial and if you have line of sight on which medical conference you expect to present the final data. I understand the interim data is being presented at ESMO, but just wanted to get a sense of timing of the presentation of final data.

非常感謝您回答我的問題。首先，我想知道您是否可以告訴我們 3550 試驗最終頂線數據的發佈時間，以及您是否了解您希望在哪個醫學會議上展示最終數據。我了解 ESMO 正在展示中期數據，但只是想了解最終數據展示的時間安排。

Sure. Hi, Ram. It's Greg. I could take that one. As you know, Ram, as we continue to be in dose escalation, it's always difficult to predict what your recommended Phase 2 dose in your MTD is going to be when you -- once again, when you see such a clean safety profile. That's why we've made the decision to escalate from 150 to 200. So when you think about it, it takes a couple of months to get a cohort enrolled, treated, and completed with data.

當然。嗨，拉姆。是格雷格。我可以接受那個。正如你所知，Ram，隨著我們繼續劑量遞增，當你再次看到如此清晰的安全狀況時，總是很難預測你的 MTD 中推薦的第 2 階段劑量是多少。這就是為什麼我們決定從 150 人升級到 200 人。因此，當您考慮一下時，需要幾個月的時間才能完成隊列的登記、治療並完成數據處理。

So we won't make a decision until -- on the MTD, which is really the driver of the final data for the Phase 1, until we establish the recommended Phase 2 dose in MTD. So we're a few months away from that for sure. That's why we're saying it's later in the fall. And then within a few months of that, we'll initiate our Phase 2.

因此，我們不會在 MTD 上做出決定，這實際上是第一階段最終數據的驅動因素，直到我們在 MTD 中確定推薦的第二階段劑量。所以我們肯定還有幾個月的時間。這就是為什麼我們說是在秋季晚些時候。然後在幾個月內，我們將啟動第二階段。

Regarding with the timing of a conference around the final data, I don't think we'll have final data in time for ASH, for sure. So it would be a conference later in the winter or early spring for the final data. But we may release that as a press release even before that, a top-level press release.

關於圍繞最終數據召開會議的時間，我認為我們肯定不會及時獲得 ASH 的最終數據。因此，最終數據將在冬末或早春召開。但我們甚至可能在此之前將其作為新聞稿發布，這是一份頂級新聞稿。

What I would add just to expand on that is -- just for those who don't really understand it is MTD is an important milestone for the company. And it's a good thing. When you're not hitting MTD, that means your product is still working. And you may have more effectiveness as you climb that ladder.

我想補充一點，只是為了擴展這一點——對於那些不太了解 MTD 的人來說，MTD 是公司的一個重要里程碑。這是一件好事。當您沒有達到 MTD 時，這意味著您的產品仍在運行。當你攀登階梯時，你可能會更有效率。

Great. And also, I wanted to ask about where in the treatment continuum you see 3550 potentially being most likely to be deployed within the context of AML specifically?

偉大的。另外，我想問一下，在治療連續體中，您認為 3550 最有可能在 AML 的背景下部署？

Yeah, that's a great question, Ram. It's something we think about every day, obviously. So our current study is monotherapy. And that's still our base case plans is to hopefully in Phase 2, if we see a compelling efficacy signal -- and what I mean by that is a significant number of durable CRs, not just blasts or reductions, but durable CRs -- we would obviously pursue an accelerated strategy because these are patients, as you know, that don't have any effective or even approved options. We're talking about relapsed/refractory AML and high-grade MDS.

是的，這是一個很好的問題，拉姆。顯然，這是我們每天都在思考的事情。所以我們目前的研究是單一療法。這仍然是我們的基本案例計劃，希望在第二階段，如果我們看到令人信服的功效信號——我的意思是大量持久的CR，不僅僅是爆炸或減少，而是持久的CR——我們會顯然追求加速策略，因為正如你所知，這些患者沒有任何有效的甚至批准的選擇。我們談論的是複發/難治性 AML 和高級別 MDS。

So that's our monotherapy approach. And by the way, we're including I think, as you know, the minimal residual disease cohort in our Phase 2, because that's a population of patients who have a high unmet need, have a -- virtually all of them will relapse, and we're essentially treating lower volume leukemia. So the MDR -- the MRD cohort is very important to us.

這就是我們的單一療法。順便說一句，我認為，正如你所知，我們將微小殘留病隊列納入我們的第二階段，因為這是一群需求未得到滿足的患者，幾乎所有人都會復發，我們基本上是在治療低容量白血病。因此，MDR——MRD 群體對我們來說非常重要。

Ultimately, I believe that the drug could be moved up in combination with standard-of-care chemotherapy. While we're continuing our monotherapy expansion cohorts in Phase 2, we will initiate a combination trial most likely with venetoclax and azacytidine, which is the most commonly used regimen in the relapsed setting. It's also, as you know, used in frontline setting.

最終，我相信該藥物最終可以與標準化療相結合。當我們在第二階段繼續我們的單一療法擴展隊列時，我們將啟動一項最有可能使用維奈托克和阿扎胞苷的聯合試驗，這是複發環境中最常用的治療方案。如您所知，它也用於前線環境。

There is a lot of published data that NK cells and hypomethylating agents, including both azacytidine and decitabine, are synergistic and work together in AML models ex vivo. There's also a lot of evidence that venetoclax, as well as the hypomethylating agents, are not toxic to NK cells. So it makes a lot of sense to combine the engager with a standard-of-care chemotherapy, and probably the perfect regimen would be venetoclax-azacytidine. So that will be done in the future as well.

有大量已發表的數據表明，NK 細胞和低甲基化劑（包括氮胞苷和地西他濱）在 AML 離體模型中具有協同作用並共同發揮作用。還有大量證據表明 Venetoclax 以及低甲基化藥物對 NK 細胞沒有毒性。因此，將接觸器與標準護理化療相結合是很有意義的，完美的治療方案可能是維奈托克-氮胞苷。所以將來也會這樣做。

Great, very helpful color. I wanted to switch gears now to talk about your B7-H3-targeted TriKE and ask if you can provide any additional color around the preclinical data previously announced, as well as give us a sense of when it might be presented at a medical conference.

很棒，非常有用的顏色。我現在想換個話題來談談你們針對 B7-H3 的 TriKE，並詢問你們是否可以為之前宣布的臨床前數據提供任何額外的信息，並讓我們了解何時可能在醫學會議上展示這些數據。

And also, if you have any thoughts on the current B7-H3 competitive landscape, especially in terms of how that compares to other kind of canonical targets that have emerged as being of interest in the context of oncology. Thank you.

另外，如果您對當前 B7-H3 的競爭格局有任何想法，特別是與腫瘤學背景下感興趣的其他類型的規範目標相比如何。謝謝。

Martin, do you want to handle that one? Or Greg, you do want -- (multiple speakers)

馬丁，你想處理那個嗎？或者格雷格，你確實想要——（多個發言者）

Greg, why don't you go ahead, and then I can try and --

格雷格，你為什麼不繼續，然後我可以嘗試——

No, I was just going say Martin has done all the work on it, Ram. So I'll have Martin present it because it's really been his project.

不，我只是想說馬丁已經完成了所有工作，拉姆。所以我會讓馬丁來展示它，因為這確實是他的項目。

Yes, I mean, well, actually, the B7-H3 TriKE that we are matriculating through preclinical studies was developed by Jeff Miller and his colleagues at the University of Minnesota. And Jeff and colleagues have published on this product candidate already.

是的，我的意思是，事實上，我們通過臨床前研究進行註冊的 B7-H3 TriKE 是由傑夫·米勒 (Jeff Miller) 和他在明尼蘇達大學的同事開發的。 Jeff 和同事已經發表了有關該候選產品的文章。

B7-H3, as you know, is ubiquitously expressed on a number of tumor targets. MacroGenics has been working on B7-H3-targeted compounds for a number of years. With our preclinical data for TriKE, we see using NK cells as a viable therapeutic modality to very specifically target and kill B7-H3 expressed in cancers.

如您所知，B7-H3 在許多腫瘤靶標上普遍表達。 MacroGenics 多年來一直致力於 B7-H3 靶向化合物的研究。根據 TriKE 的臨床前數據，我們發現使用 NK 細胞作為一種可行的治療方式，可以非常特異性地靶向並殺死癌症中表達的 B7-H3。

Today, we've looked at ovarian cancer, breast cancer, and prostate cancer, to name a few. And we've seen good killing in vitro cell assays in our animal models. Positioning wise, I think that it does provide an additional therapeutic agent for physicians to consider as they move forward with the comprehensive treatment plan for their patients. So I think that sums it up.

今天，我們研究了卵巢癌、乳腺癌和前列腺癌等。我們在動物模型中看到了良好的體外細胞殺傷效果。從定位角度來看，我認為它確實為醫生在為患者制定綜合治療計劃時提供了一種可以考慮的額外治療劑。所以我認為這就是總結。

Great. And then just lastly, I was wondering if you could comment at all on potential combinatorial regimens that you view as most ideal for any and all of your other earlier stage investigational TriKE candidates. Thank you.

偉大的。最後，我想知道您是否可以對您認為對任何和所有其他早期研究 TriKE 候選人來說最理想的潛在組合方案發表評論。謝謝。

Well, in -- when you talk combinational therapies, it certainly comes to mind the Keytruda and Opdivo to protect T cells. But that being said, we are developing dual-targeting TriKEs. And the idea there is to assist in cutting off immune escape. So we have dual-targeting TriKEs that target CD138, which is present on cancer stem cells.

好吧，當您談論聯合療法時，人們肯定會想到保護 T 細胞的 Keytruda 和 Opdivo。但話雖如此，我們正在開發雙目標 TriKE。這個想法是幫助切斷免疫逃逸。因此，我們有針對癌症幹細胞上存在的 CD138 的雙靶向 TriKE。

We have ones that go after EGFR, and GFR-3 for example, PD-L1 combination TriKE. So the platform is very versatile. And that allows us to utilize multiple-targeting domains with a single TriKE. We could, for example -- we have, for example, a CD-19 TriKE, and we could co-administer that with CD33 with our GTB-3550. It could be done. But it's, I think, more efficient to make a dual-targeting CD19, CD33 TriKE.

我們有針對 EGFR 和 GFR-3 的藥物，例如 PD-L1 組合 TriKE。所以該平台的用途非常廣泛。這使我們能夠利用單個 TriKE 來利用多個目標域。例如，我們可以——例如，我們有一個 CD-19 TriKE，我們可以將其與 CD33 和 GTB-3550 共同管理。這是可以做到的。但我認為，製作雙靶向 CD19、CD33 TriKE 更有效。

So it's really the dual targeting strategy that, I think, to a large extent, we're focused on more than trying to determine which TriKE we should pair with, which -- other standard-of-care therapy.

因此，我認為，這實際上是雙重靶向策略，在很大程度上，我們關注的不僅僅是試圖確定我們應該與哪種 TriKE 配對，哪種 - 其他標準護理療法。

I just want to add to that, Martin, that it's a reasonable question because generally, historically in oncology, it's always been about combination, right? We're obviously going to pursue -- seeking a signal as monotherapy because it's a much less challenging regulatory path if it's just used as a single agent.

我只是想補充一點，馬丁，這是一個合理的問題，因為一般來說，在腫瘤學的歷史上，它總是與組合有關，對嗎？顯然，我們將尋求單一療法的信號，因為如果它僅用作單一藥物，那麼監管路徑的挑戰性要小得多。

However, we're going to go where the science tells us to go. And there's a lot of strong rationale scientifically to combine TriKEs with -- as Martin mentioned, checkpoint inhibitors as well as standard-of-care chemotherapy. I do think we need to initiate combination studies very early into development, literally after we have a couple of cohorts of single agent safety data.

然而，我們要去科學告訴我們去的地方。正如 Martin 提到的，將 TriKE 與檢查點抑製劑以及標準護理化療結合起來有很多強有力的科學依據。我確實認為我們需要在開發的早期就開始聯合研究，實際上是在我們獲得了幾組單藥安全數據之後。

So, we're going to start doing this with AML with Ven-Aza, as I mentioned, because the science is really telling us to go there. And we'll look at every possible solid tumor combination as well with our solid tumor TriKEs and be guided by the science, as well as making sure there's a clear registration pathway for that combination.

因此，正如我提到的，我們將開始使用 Ven-Aza 進行 AML 治療，因為科學確實告訴我們應該這樣做。我們將研究每種可能的實體瘤組合以及我們的實體瘤 TriKE，並以科學為指導，並確保該組合有明確的註冊途徑。

Thank you very much.

非常感謝。

Tony Butler, ROTH Capital.

托尼·巴特勒，羅斯資本。

Yes, thanks very much. Two questions, if I may. The first is maybe for Greg or Martin. In clinicaltrials.org, it actually states the Phase 1/2 study for 3550 is enrolling, obviously, Masonic Cancer Center at University of Minnesota. But there's also Wisconsin that is listed as well but not recruiting. And I'm just curious, will you open that side for 3550 or wait for the Phase 2? That's question one.

是的，非常感謝。如果可以的話，有兩個問題。第一個可能是格雷格或馬丁的。在 ClinicalTrials.org 上，它實際上指出 3550 名患者的 1/2 期研究顯然正在明尼蘇達大學共濟會癌症中心入組。但威斯康星州也被列入名單，但沒有招聘。我只是好奇，你會為 3550 打開那一側還是等待第 2 階段？這是問題一。

Question two is, you spend a little bit of time, Martin and Greg, talking about other TriKEs. But I think -- at least, what was new to us is this notion of sort of second-generation TriKEs, which have demonstrated greater potency, greater activity, greater cytotoxicity. And I just wondered if you would just spend a minute on those.

問題二是，馬丁和格雷格，你們花了一點時間談論其他 TriKE。但我認為——至少，對我們來說新的是第二代 TriKE 的概念，它已表現出更大的效力、更大的活性和更大的細胞毒性。我只是想知道你是否願意花一點時間在這些上。

And in fact, I think the B7-H3 TriKE, for example, is one that has been created, based upon those second-generation attributes. And while you don't spend a lot of time on it, but I just thought it was important that -- you may have mentioned it because I think these thing -- it's just not a one-size-fits-all platform and seems that there are -- the flexibility -- a word that you have already used -- but also the flexibility actually leads to potentially was greater cytotoxicity, but that may be target-dependent. I appreciate any commentary around that. Thanks very much.

事實上，我認為 B7-H3 TriKE 就是基於這些第二代屬性而創建的一款。雖然你沒有花很多時間在上面，但我只是認為重要的是——你可能已經提到了它，因為我認為這些事情——它不是一個一刀切的平台，而且似乎靈活性——你已經用過的一個詞——而且靈活性實際上會導致潛在的更大的細胞毒性，但這可能是靶點依賴性的。我很欣賞對此的任何評論。非常感謝。

Sure. I can quickly answer the question about the sites and then hand it over to Martin for the discussion on the newer generation TriKE. Regarding sites and what's posted on clinicaltrials.gov is we have pre-initiated and initiated Wisconsin and we've gone through the process also with Oregon. At the time we started the process of initiating sites, frankly, we thought we would be wrapping up Phase 1 now.

當然。我可以快速回答有關站點的問題，然後將其交給 Martin 進行有關新一代 TriKE 的討論。關於網站和在 ClinicalTrials.gov 上發布的內容，我們已經預先啟動並啟動了威斯康星州，並且我們也與俄勒岡州一起完成了該過程。坦率地說，當我們開始啟動站點的過程時，我們認為現在第一階段就可以結束了。

We didn't think we would get this high -- to this high of a dose, and it made sense for us to put a hold on those sites until we initiated -- have them come in at Phase 2. They're for sure coming in the Phase 2, but they may very well come in at the tail end of Phase 1 now, but they are ready to go.

我們沒想到我們會得到這麼高的劑量，在我們啟動之前，我們有理由暫停這些網站，讓它們在第二階段進入。他們是肯定的即將進入第二階段，但他們現在很可能在第一階段結束時進入，但他們已經準備好了。

And we, by the way, are bringing on multiple new sites for the anticipated Phase 2. And we'll have up to 8 sites -- 8 to 10 total sites. And we've received a tremendous amount of interest from many of the KOLs and AML who want to participate in the Phase 2. So those initiations are starting already.

順便說一句，我們將為預期的第二階段引入多個新站點。我們將擁有最多 8 個站點——總共 8 到 10 個站點。我們收到了許多想要參與第二階段的 KOL 和 AML 的極大興趣。所以這些啟動已經開始了。

I'll hand over to Martin. I'm sorry.

我將把工作交給馬丁。對不起。

Yeah. So thanks, Tony, for the insightful question. Yes, our platform is very versatile. And our second-generation TriKEs, which are -- we're implementing across the -- all of our portfolio.

是的。謝謝托尼提出富有洞察力的問題。是的，我們的平台非常通用。我們的第二代 TriKE，我們正在我們所有的產品組合中實施。

What we've learned about how TriKE interacts with the NK cell and a target cell has led to the second-generation platform. And the key thoughts are we wanted to improve the steric interaction between the various binding domains of the TriKE molecule and the NK cell and the target cell. So in that regard, we've moved away from single chain variable fragments to nanobodies. And in that case, we have seen dramatic improvement in the potency of the drug -- of our drug candidates, in some cases, twentyfold better improvement, just because of improved the steric interaction between TriKE molecule and the NK cell.

我們對 TriKE 如何與 NK 細胞和靶細胞相互作用的了解催生了第二代平台。關鍵的想法是我們想要改善 TriKE 分子的各個結合域與 NK 細胞和靶細胞之間的空間相互作用。因此，在這方面，我們已經從單鏈可變片段轉向納米抗體。在這種情況下，我們已經看到藥物的效力顯著提高——在某些情況下，我們的候選藥物的效力提高了20 倍，這僅僅是因為TriKE 分子和NK 細胞之間的空間相互作用得到了改善。

And we've done the same investigation with respect to how the NK cell binds to the target cell. And there, in the case of the B7-H3, TriKE that you mentioned, it's a double nanobody construct with IL-15 in the middle. So we have been optimizing the platform to accentuate very -- the positive elements of TriKE therapy. And we'll continue to do so, obviously, as we grow and mature the platform.

我們對 NK 細胞如何與靶細胞結合進行了相同的研究。就您提到的 B7-H3 TriKE 而言，它是中間有 IL-15 的雙納米抗體結構。因此，我們一直在優化平台，以強調 TriKE 療法的積極因素。顯然，隨著平台的發展和成熟，我們將繼續這樣做。

Thanks, Greg and Martin, appreciate it.

謝謝格雷格和馬丁，非常感謝。

And ladies and gentlemen, at this time, we've exhausted the audio questions. I'd like to turn the floor back over for any offline questions.

女士們先生們，現在我們已經問完了音頻問題。如果有任何線下問題，我想轉回來。

And we're showing no offline questions. So at this point, I'd like to close the question-and-answer session. And I'd like to turn the floor back over to Tony Cataldo for any closing remarks.

我們沒有顯示任何離線問題。至此，我想結束問答環節。我想請託尼·卡特多 (Tony Cataldo) 發表結束語。

All right. Thank you. And thanks, everybody. I know all of you would like to -- got an update on patients 10, 11, and 12. And as Greg was articulating, we actually have been selected to do an oral presentation at the ESMO Conference in September. And because of that, we're under an embargo prohibiting us to release this kind of data. This is actually good news for GT, results presented at a major conference like this. We see much more coverage than a typical press release.

好的。謝謝。謝謝大家。我知道你們所有人都想了解 10、11 和 12 號患者的最新情況。正如 Greg 所說，我們實際上已被選中在 9 月份的 ESMO 會議上進行口頭報告。因此，我們受到禁運，禁止我們發布此類數據。這對於 GT 來說實際上是個好消息，在這樣的大型會議上公佈的結果。我們看到的報導比典型的新聞稿要多得多。

I want to thank everyone for listening to our second quarter of 2021 corporate update call, and for the continued support of our shareholders. We additionally appreciate the courageous participation of the patients in our clinical trials, and the dedication of all of those trial investigators. We look forward to sharing future data readouts from our preclinical and our clinical activities as they progress. Again, thank you, everyone, and have a great weekend.

我要感謝大家收聽我們 2021 年第二季度公司最新情況電話會議，並感謝股東的持續支持。我們還感謝患者勇敢地參與我們的臨床試驗，以及所有試驗研究人員的奉獻精神。我們期待隨著臨床前和臨床活動的進展分享未來的數據讀數。再次感謝大家，祝週末愉快。

Ladies and gentlemen, with that, we'll conclude today's conference call. We do thank you for attending. You may now disconnect your lines.

女士們先生們，我們今天的電話會議就到此結束。我們非常感謝您的出席。您現在可以斷開線路。