Moleculin Biotech Inc (MBRX) 2024 Q1 法說會逐字稿

Hello, and welcome to the Moleculin Biotech first quarter 2024 quarterly update conference call and webcast. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Moleculin Biotech 2024 年第一季更新電話會議和網路廣播。（操作員指示）謹此提醒，本次會議正在錄製中。

It is now my pleasure to turn the call over to your host, Jenene Thomas, Investor Relations. Please go ahead, Jenene.

現在我很高興將電話轉給主持人投資者關係部的 Jenene Thomas。請繼續，珍妮。

Thank you, Daryl. Good morning, and welcome, everyone. At this time, I would like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the Safe Harbor provisions of the federal securities laws and are based on Moleculin's current expectations, and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements.

謝謝你，達裡爾。早上好，歡迎大家。此時，我想提醒我們的聽眾，在本次網路廣播中發表的言論可能表明管理層的意圖、信念、期望或未來預測。這些均為前瞻性陳述，涉及風險和不確定性。本次電話會議的前瞻性聲明是根據聯邦證券法的安全港條款做出的，並且基於 Moleculin 目前的預期，實際結果可能存在重大差異。因此，您不應過度依賴任何前瞻性陳述。

Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports Moleculin files with the Securities and Exchange Commission. These documents are available in the Investors section of the company's website and on the Securities and Exchange Commission's website. We encourage you to review these documents carefully.

Moleculin 向美國證券交易委員會提交的定期報告中討論了一些可能導致實際結果與此類前瞻性陳述預期結果有重大差異的因素。這些文件可在公司網站的投資者部分和美國證券交易委員會的網站上找到。我們鼓勵您仔細查看這些文件。

Additionally, certain information contained in this webcast relates to or is based on studies, publications, surveys, and other data obtained from third-party sources and the company's own estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it does not independently verify and makes no representation as to the adequacy, fairness, accuracy, or completeness of, or that any independent source verified any information obtained from third-party source. Any data discussed regarding clinical trials and progress are considered preliminary and subject to change.

此外，本網路廣播中包含的某些資訊涉及或基於從第三方來源獲得的研究、出版物、調查和其他數據以及公司自己的估計和研究。雖然該公司認為截至本簡報發布之日這些第三方來源是可靠的，但它沒有獨立驗證任何資訊的充分性、公平性、準確性或完整性，也沒有發表任何聲明，也沒有任何獨立來源驗證任何資訊從第三方來源獲得。任何有關臨床試驗和進展的討論數據均被視為初步數據，可能會發生變化。

Joining us on today's call from Moleculin's leadership team are Walter Klemp, Chairman and Chief Executive Officer; Dr. John Paul Waymack, Senior Chief Medical Officer; and Jonathan Foster, Executive Vice President and Chief Financial Officer.

參加今天 Moleculin 領導團隊電話會議的包括董事長兼執行長 Walter Klemp； John Paul Waymack 博士，資深首席醫療官；喬納森·福斯特（Jonathan Foster），執行副總裁兼財務長。

I would now like to turn the call over to Walter Klemp, Chairman and CEO. Wally, please proceed.

我現在想將電話轉給董事長兼執行長 Walter Klemp。沃利，請繼續。

Thanks, Jenene. Well, calling 2024 transformational for Moleculin would be a massive understatement. We've now been able to lock in composition of matter patent protection for annamycin, giving us market exclusivity at least through 2040. This is the gold standard for intellectual property, and it's also underpinned by orphan drug designation in both the US and the EU.

謝謝，珍妮。好吧，稱 2024 年對 Moleculin 來說是一場變革，這實在是太輕描淡寫了。我們現在已經能夠鎖定安黴素的物質成分專利保護，使我們至少在 2040 年之前擁有市場獨佔權。這是知識產權的黃金標準，它也得到了美國和歐盟孤兒藥指定的支持。

Of course, all of this proprietary protection would be meaningless if we didn't have the safety and efficacy we need to be approved and to be useful for patients. Well, now we've treated over 80 patients and counting with 0 cardiotoxicity, something that no currently approved anthracycline can claim. But most importantly, we've now shown a 60% CRc rate in second-line patients, and key opinion leaders are beginning to weigh in on what they think of this level of performance. In fact, you can hear what they're saying by checking out the Clinical Day video by clicking on the banner on the homepage of our website at moleculin.com.

當然，如果我們不具備獲得批准和對患者有用所需的安全性和有效性，那麼所有這些專有保護都將毫無意義。嗯，現在我們已經治療了 80 多名患者，而且心臟毒性為零，這是目前批准的蒽環類藥物無法做到的。但最重要的是，我們現在已經在二線患者中展示了 60% 的 CRc 率，並且關鍵意見領袖開始權衡他們對這種表現水平的看法。事實上，您可以透過點擊我們網站（moleculin.com）主頁上的橫幅觀看臨床日影片來聽聽他們的說法。

Simply put, our efficacy results in our clinical trials to date are better than any drug ever approved for use in AML, period, and with a game-changing safety profile. Look, it's impossible for me to overstate the importance of our latest data. The greatest unmet need in AML is for an effective second-line therapy. Accordingly, we prioritize recruitment of second-line patients in our latest AML clinical trial. And as you can see, we had a 60% CRc rate.

簡而言之，迄今為止，我們在臨床試驗中的療效結果優於任何已批准用於治療 AML 的藥物，並且具有改變遊戲規則的安全性。看，我怎麼強調我們最新數據的重要性都不為過。AML 最大的未滿足需求是有效的二線治療。因此，我們在最新的 AML 臨床試驗中優先招募二線患者。正如您所看到的，我們的 CRc 率為 60%。

Not only that, but we had a 50% CR rate. Nobody does that in second line. Nobody. Again, we've never seen a performance this high from any approved AML therapy, and that's why the leading experts in leukemia are beginning to take notice.

不僅如此，我們的 CR 率為 50%。第二線沒人這麼做。沒有人。同樣，我們從未見過任何已批准的 AML 療法具有如此高的性能，這就是為什麼白血病領域的領先專家開始注意到這一點。

Since we closed the clinical trial to additional second-line patients, we've now added a few more first -- patients in first line and third line. And we've seen more complete remissions, driving the overall performance up for the trial in total, and putting us now at a total of 20 patients. We'll continue this type of recruitment, especially in first line, so that we can learn as much as possible before kicking off our registration trial.

自從我們關閉了更多二線患者的臨床試驗以來，我們現在又增加了一些第一線和第三線患者。我們已經看到了更完全的緩解，從而推動了試驗的整體表現，使我們現在共有 20 名患者。我們將繼續這種類型的招聘，特別是在一線，以便我們在開始註冊試驗之前能夠盡可能多地學習。

But let's be clear, we don't believe we need any more data before proceeding with the registration-enabling trial in second line, and that's why we're about to have our End of Phase 2 meeting with the FDA. And clearly, the most important next point of information is determining how the FDA views all this. As a point of reference, our Senior Chief Medical Officer, Paul Waymack, worked for the FDA and he has a pretty well-informed point of view on this.

但我們要明確的是，我們認為在繼續進行二線註冊試驗之前我們不需要更多數據，這就是我們即將與 FDA 舉行第二階段結束會議的原因。顯然，下一個最重要的訊息是確定 FDA 如何看待這一切。作為參考，我們的高級首席醫療官 Paul Waymack 曾在 FDA 工作，他對此有非常淵博的觀點。

On that basis, we're requesting the FDA agree to an open-label single-arm trial of around 100 to 150 patients as our pivotal approval trial. This trial will be in second-line patients where there is a clear unmet medical need, as confirmed by the key opinion leaders on last week's conference call, and where we are confident that our most recent results, if repeated in this larger population, would be more than sufficient to achieve approval. In fact, we estimate we should be able to achieve approval with a performance level much lower than the one we've recently reported.

在此基礎上，我們請求 FDA 同意對大約 100 至 150 名患者進行開放標籤單組試驗，作為我們的關鍵批准試驗。這項試驗將在二線患者中進行，這些患者的醫療需求明顯未得到滿足，正如關鍵意見領袖在上週的電話會議上所證實的那樣，我們相信，如果在更大的人群中重複我們的最新結果，足以獲得批准。事實上，我們估計我們應該能夠以比我們最近報告的低得多的績效水準獲得批准。

So what does this mean for shareholders? In recent discussions, I've made no secret about the fact that we believe Moleculin is significantly undervalued. This chart on slide 7 helps explain why we believe that. If you've been following the AML space, you have undoubtedly heard about Jazz Pharma paying $1.5 billion in 2016 for VYXEOS. And that's a drug that is really only relevant to the AML space and has a relatively limited share of market. And that deal was cut pre-approval. And now you have AbbVie's venetoclax, which is generating $2 billion a year in revenue, which at typical revenue multiples implies that venetoclax could be valued at over $10 billion as a stand-alone drug.

那麼這對股東意味著什麼？在最近的討論中，我毫不掩飾我們認為 Moleculin 的價值被嚴重低估的事實。第 7 張投影片上的圖表有助於解釋我們為何相信這一點。如果您一直在關注 AML 領域，那麼您無疑聽說過 Jazz Pharma 在 2016 年斥資 15 億美元收購 VYXEOS。這種藥物實際上只與 AML 領域相關，且市場份額相對有限。該交易在獲得批准前被取消。現在，艾伯維 (AbbVie) 的 Venetoclax 每年產生 20 億美元的收入，以典型的收入倍數計算，Venetoclax 作為獨立藥物的估值可能超過 100 億美元。

What's even more illuminating though is how some of the gene targeted therapies are being valued. For example, you've got Servier, a French mid pharma company, paying nearly $2 billion for two niche-focused AML drugs, IDHIFA and TIBSOVO. We estimate their combined impact on the AML population is to potentially produce complete remission in about 6%, 6% of the overall AML population. Then you have companies like Kura and Syndax whose drugs are relevant to a fraction of the AML population and who are being valued in the billions.

更具啟發性的是一些基因標靶療法是如何被重視的。例如，法國中型製藥公司施維雅 (Servier) 斥資近 20 億美元購買了兩種專注於利基市場的 AML 藥物 IDHIFA 和 TIBSOVO。我們估計它們對 AML 族群的綜合影響有可能使 AML 整體族群中約 6%、6% 的患者完全緩解。還有像 Kura 和 Syndax 這樣的公司，它們的藥物與一小部分 AML 人群相關，並且估值為數十億美元。

In fact, let's drill down on Kura for a moment. They're roughly at the same stage as we are: Phase 2 results and looking to start a pivotal trial. But by the way, their reported performance is significantly lower than ours. And yet Kura has a $1.5 billion market cap. To show you how ridiculous this disparity is, if we had their market cap, our stock would be trading above $600 per share. And I firmly believe we have a better drug candidate that will save many more lives. This kind of disparity simply cannot continue, and we believe it's only a matter of time before the market wakes up to this.

事實上，讓我們深入研究一下 Kura。他們與我們大致處於同一階段：第二階段結果並希望開始關鍵試驗。但順便說一句，他們報告的表現明顯低於我們。然而 Kura 的市值高達 15 億美元。為了向您展示這種差異是多麼荒謬，如果我們有他們的市值，我們的股票交易價格將超過每股 600 美元。我堅信我們有更好的候選藥物可以拯救更多的生命。這種差異根本無法持續下去，我們相信市場意識到這一點只是時間問題。

In the meantime, this is an earnings call, so I need to give our EVP, CFO, Jon Foster, a chance to weigh in. Jon?

同時，這是一次財報電話會議，所以我需要給我們的執行副總裁兼財務長喬恩·福斯特一個發表意見的機會。喬恩？

Thanks, Wally. For the quarter, R&D expense was $4.3 million for the quarter, versus $5.7 million same period a year ago. The decrease of $1.4 million is mainly related to the clinical trial activity decreasing as we're winding down MB-106 and MB-107 trials as compared to a year ago. G&A expense was $2.4 million for the quarter, less than the $2.6 million in the same period last year.

謝謝，沃利。本季研發費用為 430 萬美元，去年同期為 570 萬美元。減少 140 萬美元主要與臨床試驗活動減少有關，因為與一年前相比，我們正在逐步結束 MB-106 和 MB-107 試驗。本季一般管理費用為 240 萬美元，低於去年同期的 260 萬美元。

The use of cash was higher in this period as we made some expenditures on drug supply previously accrued, leaving us with roughly $17 million in cash on hand for the quarter. Our market cap is at roughly $13 million, taking into account the 2.5 million shares outstanding, which includes prefunded warrants.

這段期間的現金使用量較高，因為我們在先前累積的藥品供應方面支出了一些費用，因此本季我們手頭上有大約 1700 萬美元的現金。考慮到 250 萬股已發行股票（其中包括預先融資的認股權證），我們的市值約為 1300 萬美元。

Our average daily trading volume is at 30,000 shares per day. And we have moved some planned expenditures from 2024 into 2025, and our cash runway now runs deeper into Q4 2024 than previously planned. Wally?

我們的每日平均成交量為 30,000 股。我們已將一些計畫支出從 2024 年推遲到 2025 年，我們的現金跑道現在比之前規劃的更深入到 2024 年第四季。沃利？

Thanks, Jon. Well, if there's one takeaway from this call, I hope it's that we believe our clinical data is strong enough to warrant approval if repeated in the context of the pivotal trial. And that's exactly where we're heading. Assuming we receive a supportive response from the FDA, we should be kicking off that pivotal trial by the end of this year. And in our view, that means we are now entering the window that is typical for exits in our industry.

謝謝，喬恩。好吧，如果這次電話會議有一個要點的話，我希望我們相信我們的臨床數據足夠強大，如果在關鍵試驗的背景下重複的話，足以保證獲得批准。這正是我們前進的方向。假設我們得到 FDA 的支持性回應，我們應該在今年年底前啟動這項關鍵試驗。我們認為，這意味著我們現在正在進入行業退出的典型視窗。

Obviously, our stock price is not yet tracking with this possibility, but we believe it eventually will. And if we're right about that, we believe shareholders will finally have an opportunity to see the kind of valuations that they deserve.

顯然，我們的股價尚未追隨這種可能性，但我們相信它最終會跟隨這種可能性。如果我們的觀點是正確的，我們相信股東最終將有機會看到他們應得的估值。

I challenge anyone considering an investment in Moleculin to just look at the data. Compare us with any other asset in the AML space. Listen to what key opinion leaders are saying about annamycin. And I promise you, when you do, you will ask yourself, how can MBRX be valued so low? My answer is, we shouldn't be. And we won't be for much longer.

我挑戰任何考慮投資 Moleculin 的人只看數據。將我們與反洗錢領域的任何其他資產進行比較。聽聽關鍵意見領袖對安黴素的看法。我向你保證，當你這樣做時，你會問自己，MBRX 的估值怎麼會這麼低？我的回答是，我們不應該這樣做。我們不會持續太久。

Now clearly, that's only my opinion, but this isn't just talk on management's part. We've been investing our own after-tax dollars in Moleculin stock because of our confidence in this opportunity.

顯然，這只是我的觀點，但這不僅僅是管理階層的言論。由於我們對這個機會充滿信心，我們一直將自己的稅後資金投資於 Moleculin 股票。

So thanks for joining us today, and we look forward to the upcoming critical news flow on our progress.

感謝您今天加入我們，我們期待即將發布的有關我們進展的重要新聞。

(Operator Instructions) Jonathan Aschoff, Roth MKM.

（操作員說明）Jonathan Aschoff，Roth MKM。

Thank you, guys, and good morning. I was curious, has there been anything else even remotely akin to allergic reactions, or is it just as was reported several weeks ago for the, I think, one patient?

謝謝你們，夥計們，早安。我很好奇，是否有其他任何與過敏反應類似的情況，或者是否像幾週前報道的那樣，我認為是一名患者？

Well, there's no new information, Jonathan, but I want to give Paul a chance to sort of weigh in, because that's an important point as it, as you know, it actually, we think, has mathematically the potential to cause our numbers to be currently actually slightly understated. But Paul, do you want to explain why that is?

好吧，沒有新的信息，喬納森，但我想給保羅一個機會來發表意見，因為這是一個重要的觀點，因為正如你所知，我們認為，實際上，從數學上講，有可能使我們的數字目前其實稍微被低估了。但是保羅，你想解釋為什麼嗎？

Yes. First, to your question, that case was a typical allergic reaction where, when the drug infusion began, the patient began to have a little wheezing, and cutting back on the rate did not stop it. It's been the only patient in whom this has happened in over 80 patients whom we have treated. So it appears to be a relatively rare event.

是的。首先，對於你的問題，該病例是一種典型的過敏反應，當開始輸注藥物時，患者開始有一點喘息，並且減少速率並沒有阻止它。這是我們治療過的 80 多名患者中唯一發生這種情況的患者。因此，這似乎是一個相對罕見的事件。

We say unfortunate because that patient was one of the 10 patients who received second-line therapy, and of course, in an intent-to-treat analysis, he counts even though he never was going to get a response since he never received more than a micro amount of the drug. So of the 10 patients, we had the six CRs, one PR. Of the three people who had no response, he was one of the three where that was because he never got the drug.

我們說不幸的是，因為該患者是接受二線治療的 10 名患者之一，當然，在意向治療分析中，即使他永遠不會得到回應，因為他從未接受過超過微量的藥物。因此，在 10 名患者中，我們獲得了 6 名 CR，1 名 PR。在三個沒有反應的人中，他是三個沒有反應的人之一，因為他從未得到過藥物。

Okay. But then we also had another one that was allergic to cytarabine, correct, Paul?

好的。但我們還有另一隻對阿糖胞苷過敏，對吧，保羅？

Yes. That was not a second-line one, though. But yes, we had one allergic reaction to cytarabine.

是的。不過，那不是二線的。但是，是的，我們對阿糖胞苷有一種過敏反應。

Okay. And I was thinking about the, what should be this quarter, the End of Phase 2 meeting. When you say 1 half '25 to start the trial, are you just being conservative and maybe it's more like the beginning of the first half? Or do you really need a year, with that decent CRc rate, to start a trial after that meeting?

好的。我正在考慮本季第二階段結束會議應該是什麼。當你說25年半開始審判時，你是否只是保守，也許這更像是上半場的開始？或者你真的需要一年的時間，以相當好的 CRc 率，在會議之後開始試驗嗎？

We are trying to -- I mean, Jonathan, we've interacted with you for a long time, I think you know we're fairly conservative and we always like to leave room for the unforeseen. Technically speaking, we should be in a position to start the trial even before the end of the year. But inevitably, in clinical trials, there's always one last thing that has to be ironed out. So we're describing it as one half '25 to give ourselves a bit of leeway, but I agree with you, it should be right at the beginning of '25.

我們正在努力——我的意思是，喬納森，我們已經與您互動了很長時間，我想您知道我們相當保守，我們總是喜歡為不可預見的情況留出空間。從技術上來說，我們應該可以在年底前開始試驗。但不可避免的是，在臨床試驗中，總有最後一件事必須解決。因此，我們將其描述為 25 年半，以便給自己留出一點餘地，但我同意你的觀點，應該是在 25 年初。

Okay. And then not to nitpick, but in that same little list of future events, there's -- this quarter, there should be the meeting, like I said, the EOP2. But then there's another line item, second half of 2026, for feedback from the EOP2 meeting. I don't really get that. Is that supposed to be something that happens after your single-arm trial?

好的。然後不是吹毛求疵，但在未來事件的同一個小清單中，有——這個季度，應該有會議，就像我說的，EOP2。但還有另一個項目，即 2026 年下半年，用於 EOP2 會議的回饋。我真的不明白。這應該是單臂試驗之後發生的事嗎？

No. That sounds like a typo.

不。這聽起來像是個錯字。

No, I'm looking at the slide right now. It's End of Phase 1 meeting first half of 2024; initiate pivotal trial, 2025. So feedback in the third quarter of this year.

不，我現在正在看幻燈片。第一階段會議將於 2024 年上半年結束； 2025 年啟動關鍵試驗。所以今年第三季反饋。

It says H2 2026 in the press release.

新聞稿中稱 H2 2026。

That's conclude the pivotal trial.

關鍵審判就此結束。

Okay.

好的。

We'll check that. Thank you, Jon.

我們會檢查一下。謝謝你，喬恩。

Yeah. Have you seen enrollments, recruitment ease, I guess, let's call it, become more easy commensurate with the additional responses you've been showing over time? How are you faring against the other clinical-stage AML competition? Because there's a decent amount of that. And has your data --

是的。您是否看到註冊、招聘變得更加容易，我想，我們可以這樣稱呼它，與您隨著時間的推移所表現出的額外回應相稱？你們在其他臨床階段 AML 競爭中表現如何？因為其中的數量相當可觀。並且有你的數據--

Yeah. There's no question that once we started to see complete remissions in second-line patients -- there's a regular conference call where all the investigators have a chance to participate and share in the information that's going on with the clinical trial, once that -- and so that information gets out pretty quickly. And once that started to happen, it was -- you could just see it. All of a sudden more and more people start recruiting, and recruiting picked up -- I mean, we saw recruitment probably triple in pace when that started to happen.

是的。毫無疑問，一旦我們開始看到二線患者的完全緩解——就會定期召開電話會議，所有研究人員都有機會參與並分享臨床試驗正在進行的信息——然後所以信息很快就會傳出去。一旦這種情況開始發生，你就可以看到它。突然間，越來越多的人開始招聘，而且招聘速度加快了——我的意思是，當這種情況開始發生時，我們看到招聘速度可能會增加三倍。

I can't really comment relative to other competitive trials, other than to say clinicians, all -- every one of these clinicians, when you sit down with them and really talk about the reality of clinical trial, it becomes glaringly apparent what they care most about is the welfare of their patients, as they should. And so even though there are clinical trials out there for targeted therapies -- and let's face it, the performance of targeted therapies has been kind of dismal. I mean it's just enough to get them approved, but it really sets a low bar. 20% CR rates, that kind of thing.

我無法對其他競爭性試驗進行真正的評論，除了說臨床醫生，所​​有這些臨床醫生中的每一位，當你與他們坐下來真正談論臨床試驗的現實時，他們關心的事情就變得顯而易見關心的是病人的福利，這是他們應該做的。因此，儘管有針對標靶療法的臨床試驗——讓我們面對現實吧，標靶療法的表現還是有點令人沮喪。我的意思是，這足以讓他們獲得批准，但這確實設定了一個很低的門檻。20% CR 率之類的。

And clinicians are not blind to that. And so if they see it, let's say, their patient might line up for FLT3 or might line up for another mutation that is -- for which there are clinical trials, but now that they realize they can achieve a 60% CR rate with annamycin, it puts a lot of pressure on them to pick our trial over somebody else. At least that's been based on our -- the nine clinical sites that we have right now.

臨床醫師對此並非視而不見。因此，如果他們看到它，比方說，他們的病人可能會排隊接受FLT3，或者可能會排隊接受另一種突變——這方面已有臨床試驗，但現在他們意識到使用安黴素可以達到60 % 的CR 率，這給他們帶來了很大的壓力，讓他們選擇我們的審判而不是其他人。至少這是基於我們現在擁有的九個臨床站點。

We're going to obviously have more clinical sites for the pivotal trial. And I think one of the most important jobs we're going to have is making sure all of those sites really understand the data, so they have the same level of enthusiasm that our current sites do.

顯然，我們將有更多的臨床地點進行關鍵試驗。我認為我們要做的最重要的工作之一是確保所有這些網站都真正理解數據，這樣他們就有與我們目前網站相同的熱情。

Great. That sounds like it bodes well for Phase 3. Thank you.

偉大的。這聽起來對第三階段來說是個好兆頭。謝謝。

Yeah. Thanks, Jonathan.

是的。謝謝，喬納森。

Jason McCarthy, Maxim Group.

傑森麥卡錫，馬克西姆集團。

Hi, guys. This is Chad on for Jason. Thanks for taking the questions. So can you give us an idea of the end values of the pivotal trials for the five approved second-line drugs? And how would that compare to the upcoming potential pivotal design?

嗨，大家好。這是查德（Chad）代替傑森（Jason）。感謝您提出問題。那麼您能否為我們介紹五種已核准的二線藥物的關鍵試驗的最終值？與即將到來的潛在關鍵設計相比如何？

So I'm going to let Paul comment on the impact on the pivotal design. But just as a point of information, in fact, there's a -- our corporate deck on the website, that's available on the website, has a slide dedicated to this question about the approval rates for the five currently approved drugs.

因此，我將讓保羅評論一下對關鍵設計的影響。但作為一個資訊點，事實上，我們的公司網站上有一張幻燈片，專門討論有關目前批准的五種藥物的批准率的問題。

And just for the record, there are five drugs that are approved for use in second-line AML in the US. Not all of them are approved in the EU. And that has a lot to do with, frankly, the relatively poor performance levels and the fact that many of these drugs were approved on the basis of a single-arm open-label trial, which the EU categorically will not utilize for drug approvals, for marketing authorizations.

鄭重聲明一下，美國有五種藥物被批准用於二線 AML。並非所有這些都獲得歐盟批准。坦白說，這與相對較差的性能水平以及許多這些藥物是在單臂開放標籤試驗的基礎上獲得批准的事實有很大關係，而歐盟絕對不會將其用於藥物批准，用於營銷授權。

But that slide in our corporate deck lists out the -- both the CR and the -- the CRH or CRI, the additional component that makes up CRc, composite CR rate. And what you'll see is the CR rates on average are 21%, some below, some above. And you get a little bit better performance because these drugs tend to produce CRIs or CRHs. But no matter how you look at the data, we're double that performance basically. So that's why we're so, frankly, bullish about our capability.

但我們公司幻燈片中的幻燈片列出了 CR 和 CRH 或 CRI，即構成 CRc 的附加組成部分，即綜合 CR 率。您將看到平均 CR 率為 21%，有的低於，有的高於。而且你會獲得更好的表現，因為這些藥物往往會產生 CRI 或 CRH。但無論你如何看待數據，我們基本上都將效能提高了一倍。坦白說，這就是為什麼我們如此看好我們的能力。

But Paul, you want to weigh in here relative to the impact on approval?

但是保羅，你想在這裡權衡一下對批准的影響嗎？

Sure. To answer the question, for the five drugs that were approved to second-line monotherapy, the number of patients vary from around 100 to 300. Now I think it's important to always recognize who is your audience, what do they want? And the answer is the FDA.

當然。要回答這個問題，對於被批准用於二線單藥治療的五種藥物，患者數量從 100 到 300 人左右不等。現在我認為重要的是要始終認識到誰是您的受眾，他們想要什麼？答案是FDA。

And for the FDA, the average response is not as important as the 95% confidence intervals. And the CR rate for these drugs was from around 15% to 30%, which does not give you overwhelming confidence and the 95% confidence interval with low numbers of patients. So when you're getting low response rates, you're going to need more patients.

對於 FDA 來說，平均響應並不像 95% 信賴區間那麼重要。這些藥物的 CR 率約為 15% 至 30%，這並不能給你壓倒性的信心，也不能給你在患者數量較少的情況下提供 95% 的置信區間。因此，當反應率較低時，您將需要更多患者。

The reason we proposed only 100 patients is, if we're getting anywhere near the 60% response rate, when you do 95% confidence intervals for that, you don't need a lot of patients to show you're getting a big effect, because the FDA is going to worry about the lower limit of the 95% confidence interval. So although this would be a rather low number of patients from a perspective of other drugs, because our response rates are so unprecedented, we can propose a lower rate.

我們建議只使用 100 名患者的原因是，如果我們達到接近 60% 的緩解率，那麼當您為此進行 95% 的置信區間時，您不需要大量患者來表明您獲得了很大的效果，因為FDA 會擔心95% 信賴區間的下限。因此，儘管從其他藥物的角度來看，這將是一個相當低的患者數量，但由於我們的反應率如此之高，我們可以提出一個較低的比率。

Full disclosure, the only concern we have is we are a combination therapy, as opposed to those other four drugs. And that might cause the FDA to say, well, we generally want a randomized trial for a combination therapy. But again, it's been true in the past, but there has never been a drug with this response rate. This is just unprecedented. So we think we, therefore, have a case to say, when it's that high, you have to do a different general plan for the final clinical trial of the drug.

全面披露，我們唯一擔心的是我們是一種聯合療法，而不是其他四種藥物。這可能會導致 FDA 說，我們通常希望對聯合療法進行隨機試驗。但話又說回來，過去確實如此，但從來沒有一種藥物有這樣的反應率。這簡直是史無前例的。因此，我們認為我們有理由說，當它這麼高時，你必須為藥物的最終臨床試驗制定不同的總體計劃。

Got it. Okay, thanks. That was really helpful. And then, while of course second line is the focus now, can you maybe just speak a bit to the plan eventually for first line and sort of the opportunity there?

知道了。好的謝謝。這真的很有幫助。然後，雖然現在第二線當然是焦點，但您能否談談最終第一線的計劃以及那裡的機會？

Yeah. Again, let me maybe kick that off, but then have Paul weigh in. We mentioned in the prepared remarks here that we're continuing to recruit first-line patients into the existing MB-106 trial. And the reason we're doing that is maybe twofold. But in general, we just want additional data. We want additional knowledge. As Paul said, the response in second line is unprecedented.

是的。再說一遍，也許讓我先開始討論，然後讓保羅參與其中。我們在此準備好的評論中提到，我們將繼續招募第一線患者參與現有的 MB-106 試驗。我們這樣做的原因可能是雙重的。但總的來說，我們只需要額外的數據。我們需要更多的知識。正如保羅所說，二線的反響是前所未有的。

You would expect, generally speaking, an even better response in first-line patients. And in fact, so far, that's what we're seeing. Now it's on a small N, we've only had three first-line patients so far. So you need to be careful with that. But as expected, that we're seeing a slightly better response rate.

一般來說，您會期望第一線患者獲得更好的反應。事實上，到目前為止，這就是我們所看到的。現在已經是小N了，到目前為止我們只有三位第一線患者。所以你需要小心這一點。但正如預期的那樣，我們看到的回應率稍好一些。

It becomes important, I think, on two levels. One, from an approval standpoint. If we're successful in negotiating a single-arm trial with the FDA, then it undoubtedly means we will have to eventually run a confirmatory Phase 3 post-approval. That's a high-class problem because you're, at that point, you're already generating revenue and running a trial in parallel.

我認為，它在兩個層面上變得非常重要。一、從認可的角度來看。如果我們在與 FDA 的單臂試驗談判中取得成功，那麼這無疑意味著我們最終將不得不在批准後進行確認性的第 3 階段。這是一個高級問題，因為此時您已經在產生收入並並行運行試驗。

But when we think about the trial, the Phase 3 trial design we would most prefer, it turns out it's probably a first-line trial where you're comparing head-to-head against, let's say, the existing 7+3 therapy. And so the more we know about our drug's performance in first line before we run that trial, the better we are at structuring that trial. That's, let's say, one important factor.

但當我們考慮試驗時，我們最喜歡的 3 期試驗設計，事實證明這可能是一線試驗，您正在與現有的 7+3 療法進行正面比較。因此，在進行該試驗之前，我們對藥物在一線的表現了解得越多，我們就越能更好地建構該試驗。可以說，這是一個重要因素。

The other important element here is in terms of exit opportunity for big pharma. They're already looking -- we know they're already looking at us and watching what we're doing. And once you start to understand the drug, you realize it's not just -- it's not going to be simply a second-line treatment for AML. That's our pathway for approval, and we love that pathway, but the drug is going to be so much more than that.

這裡的另一個重要因素是大型製藥公司的退出機會。他們已經在看著我們——我們知道他們已經在看著我們並觀察我們在做什麼。一旦您開始了解這種藥物，您就會意識到它不僅僅是 AML 的二線治療藥物。這是我們獲得批准的途徑，我們喜歡這條途徑，但藥物的作用遠不止於此。

In our view, it will become the standard of care, most likely displacing all other anthracyclines, not just in AML but in many indications, which, again, goes back to why the comparison to drugs with companies like Kura is so ridiculous, because annamycin is going to be so much more important to the medical community at large. But Paul, do you want to comment at all on the strategy behind the first line versus second line?

我們認為，它將成為護理標準，很可能取代所有其他蒽環類藥物，不僅在AML 方面，而且在許多適應症方面，這又回到了為什麼與Kura 這樣的公司的藥物進行比較是如此荒謬，因為安黴素對於整個醫學界來說將變得更加重要。但是保羅，你想對第一線和第二線背後的策略發表評論嗎？

Sure. And I would agree fully, first-line therapy is the ultimate indication because everybody at some point is first line. Only some patients progress to second line. However, again, focus on your audience, focus on FDA. FDA looks and sees there are lots of drugs that have been approved to treat first-line therapy for AML.

當然。我完全同意，第一線治療是最終的適應症，因為每個人在某些時候都是一線治療。只有部分患者進展至二線。然而，再次強調，關注你的受眾，關注 FDA。FDA 發現許多藥物已被批准用於治療 AML 的一線療法。

However, the five drugs for treating second-line therapy are all for subsets of the population, for patients with FLT3 mutations, with isocitrate dehydrogenase mutations. But that's, combined, less than half of the population. A majority of patients who need second-line therapy, there is no FDA drug approved and indicated for that. And that is the FDA definition of an unmet medical need, which lowers the bar dramatically as far as patient numbers, trial design and the like.

然而，用於治療二線療法的五種藥物均針對人群子集，針對具有 FLT3 突變、異檸檬酸脫氫酶突變的患者。但這加起來還不到總人口的一半。對於大多數需要二線治療的患者，FDA 尚無批准並適用的藥物。這就是 FDA 對未滿足的醫療需求的定義，它大大降低了病患數量、試驗設計等方面的標準。

So recognizing that, that that's the easiest, quickest way to an approvable NDA, that's where we're going first. But we have not given up on first-line therapy. Indeed, although we have shut down enrollment in our 106 trial for second line, because we have enough data to power a second-line pivotal trial, we are continuing to enroll first-line therapy patients so that we will eventually have enough data to power a first-line study, because that will be our second Phase 3 study.

因此，認識到這是獲得批准的 NDA 的最簡單、最快的方法，這就是我們首先要做的。但我們並沒有放棄一線治療。事實上，儘管我們已經停止了二線 106 項試驗的招募，但因為我們有足夠的數據來支持二線關鍵試驗，我們仍在繼續招募一線治療患者，以便我們最終將有足夠的數據來支持一線研究，因為這將是我們的第二個3 期研究。

Okay, awesome. Thanks for taking the questions and congrats again on all the progress.

好吧，太棒了。感謝您提出問題並再次祝賀所有進展。

Thanks, Chad.

謝謝，查德。

Vernon Bernardino, H.C. Wainwright.

伯納迪諾，H.C.溫賴特。

Hi, everyone. Thanks for taking my question and congrats on the progress as well. So given the date, today's date, and the milestones we expect to see first half of this year, obviously, other than announcing the conclusion and then having conducted EOP meeting with the FDA, what can we expect as far as additional results from the MB-106 trial and as well as the End of Phase 2 meeting? And do you anticipate announcing what you're going to announce at MB-106 before the End of Phase 2 meeting -- having conducted the End of Phase 2 meeting? Or will you just announce the End of Phase 2 meeting or will you actually also announce perhaps some of the details of the discussion with the FDA? Thanks.

大家好。感謝您提出我的問題，也祝賀我的進展。因此，鑑於日期、今天的日期以及我們預計今年上半年將看到的里程碑，顯然，除了宣布結論並隨後與 FDA 舉行 EOP 會議之外，我們還能對 MB 的其他結果有何期待-106 審判以及第二階段會議結束？您是否預計在第二階段會議結束之前宣布您將在 MB-106 上宣布的內容—已經進行了第二階段會議結束？或者您只是宣布第二階段會議結束，還是實際上也宣布與 FDA 討論的一些細節？謝謝。

Sure. Jon, you're the kind of the keeper of important dates and announcements. Let me hand this off to you so you could kind of navigate this.

當然。喬恩，你是那種注重重要日期和公告的人。讓我把這個交給你，這樣你就可以解決這個問題。

Sure. Vernon, we're not going to announce when we're having the meeting. We're staying true with what we've said earlier. We will have it by the end of June. We don't want to give the specific date out, just because we don't want people calling around that date and bugging us, to be quite honest. And we'll have feedback in early Q3 and we'll share that with the public. And we're very excited about that potential of what that feedback is.

當然。弗農，我們不會宣布會議時間。我們將恪守我們之前所說的。我們將在六月底收到它。老實說，我們不想透露具體日期，只是因為我們不希望人們在該日期前後打電話來騷擾我們。我們將在第三季初收到回饋，並與公眾分享。我們對回饋的潛力感到非常興奮。

And as we've said before, we think long and hard about our key events, and we try to be conservative to be sure we're going to make those. And we're going to make those two dates.

正如我們之前所說，我們對我們的關鍵事件進行了長期而認真的思考，並且我們努力保持保守以確保我們能夠完成這些事件。我們將安排這兩個日期。

I think it's important to add, because you did ask about the MB-106 trial. Yes, it's ongoing. I think it's unlikely, given the time span between now and when the FDA meeting will occur, I think it's relatively unlikely that we'll have additional MB-106 data to release between now and then. It's not impossible, but it's probably not likely.

我認為補充很重要，因為您確實詢問了 MB-106 試驗。是的，它正在進行中。我認為這不太可能，考慮到從現在到 FDA 會議舉行的時間跨度，我認為從現在到那時我們不太可能發布額外的 MB-106 數據。這並非不可能，但可能性不大。

Yeah, we'll probably announce -- give an update of the MB-106 on the first-line patients in August with our quarterly earnings.

是的，我們可能會在 8 月公佈季度收益，並在 8 月公佈 MB-106 在第一線患者中的最新情況。

Okay. Thanks for that fine detail. I appreciate it.

好的。謝謝你的細節。我很感激。

Thank you. We have reached the end of our question-and-answer session. And with that, that does conclude today's teleconference. We appreciate your participation. You may disconnect at this time. And enjoy the rest of your day.

謝謝。我們的問答環節已經結束。今天的電話會議到此結束。我們感謝您的參與。此時您可以斷開連線。並享受剩下的一天。