Moleculin Biotech Inc (MBRX) 2024 Q3 法說會逐字稿

Greetings, and welcome to the Moleculin Biotech quarterly update conference call and webcast.

大家好，歡迎參加 Moleculin Biotech 季度更新電話會議和網路廣播。

(Operator Instructions)

（操作員指令）

As a reminder, this conference is being recorded.

提醒一下，本次會議正在錄音。

It's now my pleasure to introduce your host, Jenene Thomas, Investor Relations.

現在我很高興介紹您的主持人，投資者關係部 Jenene Thomas。

Please go ahead, Jenene.

請繼續，詹妮娜。

Thank you, Kevin.

謝謝你，凱文。

Good morning, and welcome, everyone.

早上好，歡迎大家。

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.

此時，我想提醒我們的聽眾，本次網路廣播的言論可能表明管理層的意圖、信念、期望或未來預測。

These are forward-looking statements and involve risks and uncertainties.

這些是前瞻性陳述，涉及風險和不確定性。

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.

本次電話會議中的前瞻性聲明是根據聯邦證券法的安全港規定並基於 Moleculin 當前的預期做出的，實際結果可能存在重大差異。

As a result, you should not place undue reliance on any forward-looking statements.

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.

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所預期的結果有重大差異的因素。

These documents are available in the Investors section of the company's website and on the Securities and Exchange Commission's website.

這些文件可在公司網站的投資者部分以及美國證券交易委員會的網站上查閱。

We encourage you to review these documents carefully.

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.

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。

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.

儘管本公司認為截至本報告發布之日這些第三方來源是可靠的，但它並未獨立核實，也不對從第三方來源獲得的任何資訊的充分性、公平性、準確性或完整性作出任何陳述，也不保證任何獨立來源已核實從第三方來源獲得的任何資訊。

Any data discussed regarding clinical trials and progress are considered preliminary and subject to change.

任何有關臨床試驗和進展討論的數據都被視為初步數據，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.

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

I would now like to turn the call over to Mr. Klemp.

現在我想將電話轉給克萊普先生。

Wally, please proceed.

沃利，請繼續。

Thank you, Jenene.

謝謝你，詹妮娜。

Well, investors who have been following our presentations are not new to this, but we are resolute in our belief that our current market cap is nowhere close to reflecting the value of a Phase III company like Moleculin, especially in light of how much risk we believe we have removed from the pathway to approval.

好吧，一直關注我們演講的投資者對此並不陌生，但我們堅信，我們目前的市值遠遠不能反映像 Moleculin 這樣的 III 期公司的價值，特別是考慮到我們認為已經從審批道路上消除了多少風險。

Ultimately, we believe that just creates more opportunity for investors today.

最終，我們相信這只會為今天的投資者創造更多的機會。

And I'm confident that as our miracle trial unfolds, the magnitude of this opportunity will become more apparent.

我相信，隨著我們的奇蹟試驗的展開，這個機會的重要性將變得更加明顯。

If you're new to Moleculin and asking why this opportunity even exists, we believe that for nearly a decade now, the AML space has been betting on a big payoff from targeted therapies.

如果您是 Moleculin 的新手，並且想知道為什麼會有這樣的機會，那麼我們相信，近十年來，AML 領域一直在押注標靶治療帶來巨大回報。

But the reality is that these new targeted therapies simply haven't delivered.

但現實是，這些新的標靶療法根本沒有效果。

In fact, they've been a big disappointment.

事實上，他們確實令人大失所望。

And it's evidenced by the fact that venetoclax, which is an untargeted chemotherapy has created far more value in the last five years than all of the targeted therapies combined in AML.

事實證明，非標靶化療藥物維奈克拉在過去五年中創造的價值遠遠超過了 AML 所有標靶療法的總價值。

Now the fact is that anthracycline continue to be among the most used and most effective cancer therapies available.

現在的事實是蒽環類藥物仍然是最常用且最有效的癌症治療方法之一。

They're used in 32% of breast cancers, half of all AML patients, 70% of lymphomas and actually 60% of all childhood cancers.

32% 的乳癌、一半的 AML 患者、70% 的淋巴瘤以及 60% 的兒童癌症都需要使用這種藥物。

So if you're looking for a true disruptor opportunity, the annamycin story deserves your attention.

因此，如果您正在尋找真正的顛覆機會，那麼 annamycin 的故事值得您關注。

What we believe we have is a safer, more effective anthracycline than has ever been possible.

我們相信，我們所擁有的蒽環類藥物比以往任何時候都更安全、更有效。

And it's enabling clinicians to treat with higher dosages and for a greater number of cycles than was ever thought feasible.

它使臨床醫生能夠採用比以往認為可行的更高劑量和更多周期進行治療。

And we aren't just filling an unmet need for more than half of AML patients.

我們不只是滿足了一半以上 AML 患者尚未滿足的需求。

We're talking about potential uses far beyond just AML.

我們討論的潛在用途遠不止反洗錢。

Now in this presentation, we are focusing just on the latest update.

現在，在本次演示中，我們只關注最新更新。

So if you're new to Moleculin, I urge you to review our online presentations and watch our explanatory videos.

因此，如果您是 Moleculin 的新用戶，我建議您查看我們的線上演示並觀看我們的解釋影片。

With that said, though, just to hit the high spots of the Moleculin opportunity, the key takeaways from this slide are that unlike currently available anthracycline, annamycin was designed to be 100% non-cardiotoxic.

儘管如此，為了抓住 Moleculin 機會的亮點，這張投影片的關鍵要點是，與目前可用的蒽環類藥物不同，安那黴素被設計為 100% 無心臟毒性。

It avoids cross-resistance with the leading AML drugs, which means it has the potential to work when the others fail.

它避免了與主要的 AML 藥物產生交叉抗藥性，這意味著當其他藥物失效時，它有可能發揮作用。

And annamycin is patent protected through 2040, which is a remarkably long remaining patent life for a Phase III cancer drug.

而 annamycin 的專利保護期將持續到 2040 年，對於 III 期抗癌藥物而言，這已經是相當長的專利保護期了。

And in part, because targeted therapies have been such a disappointment, we still have almost 60% of the AML population without an acceptable treatment option.

部分原因是由於標靶治療效果令人失望，我們仍有近 60% 的 AML 患者沒有可接受的治療選擇。

There is still an incredible unmet need in AML.

反洗錢領域仍存在大量未滿足的需求。

So let me now ask our Senior Chief Medical Officer, Paul -- Dr. Paul Waymack, to provide an update on patient data and our startup of the Phase III MIRACLE trial.

現在，請允許我請我們的高級首席醫療官保羅 - 保羅·韋馬克博士提供有關患者數據的最新信息以及我們啟動第三階段 MIRACLE 試驗的情況。

Paul?

保羅？

Thank you, Wally.

謝謝你，沃利。

Well, as Wally said, there is an incredible unmet need in AML.

嗯，正如沃利所說，反洗錢領域存在著大量未滿足的需求。

And specifically, it is for those patients who either don't respond or quickly relapse after first-line induction therapy.

具體來說，它適用於那些對一線誘導治療沒有反應或很快復發的患者。

As you can see from our most recent Phase II data, this is where annamycin excels.

從我們最近的 II 期數據可以看出，這正是 annamycin 的優勢所在。

As previously reported, we saw a 50% complete remission rate in these second-line patients, which is more than double the performance you would expect from existing therapies.

正如先前報導的那樣，我們在這些二線患者中看到50%的完全緩解率，這是現有療法預期效果的兩倍多。

Since our last update, the bone marrow transplants in subjects with the response have increased to four of the nine patients.

自我們上次更新以來，對治療有反應的受試者的骨髓移植數量已增加到 9 名患者中的 4 名。

This is remarkable for second-line patients as bone marrow transplant is the key to potentially long-term durability, as you will see in the next slide.

對於二線患者來說，這非常了不起，因為骨髓移植是實現潛在長期耐久性的關鍵，正如您將在下一張幻燈片中看到的那樣。

And the durability of these responses just keeps getting better.

而這些反應的持久性也越來越好。

We're now up to a median of eight months and still climbing.

現在，中位數已達到 8 個月，並且仍在攀升。

In addition, these responses are considered high-quality complete responses by the hematology community with 78% of them recorded as negative in terms of measurable, residual disease, and now with 44% of our responders bridging to a potentially curative bone marrow transplant.

此外，血液學界認為這些反應是高品質的完全反應，其中 78% 在可測量的殘留疾病方面記錄為陰性，現在 44% 的反應者正在接受潛在的治癒性骨髓移植。

Again, for second-line subjects, we believe that our durability is shaping up as truly a game changer.

再次，對於二線科目，我們相信我們的耐用性正在真正改變遊戲規則。

Of course, it's this remarkable response rate that has led FDA to encouraging us to use an adaptive trial design for a Phase III approval trial, as we call it, the MIRACLE trial.

當然，正是這種顯著的反應率使得 FDA 鼓勵我們在第三階段批准試驗中使用自適應試驗設計，我們稱之為 MIRACLE 試驗。

For those new to this trial, it begins with a Part A, which is designed to establish an optimum dose for annamycin, and then it expands that dose into additional subjects in Part B.

對於新參與試驗的受試者，試驗從 A 部分開始，旨在確定 annamycin 的最佳劑量，然後將該劑量擴展到 B 部分的其他受試者。

This trial design is responsive to a new FDA initiative called Project Optimus, the purpose of which is to avoid simply defaulting to the maximum tolerated dose and instead seeks a balance between safety, tolerability and efficacy.

該試驗設計響應了 FDA 的一項新舉措“Project Optimus”，其目的是避免簡單地默認最大耐受劑量，而是尋求安全性、耐受性和有效性之間的平衡。

It's worth clarifying though that we don't view this dose optimization process is resulting in any increased risk in approval risk.

但值得澄清的是，我們並不認為這個劑量優化過程會導致審批風險的增加。

To the contrary, the FDA actually specified the two doses they would prefer to see compared as the two doses in the MB-106 trial that demonstrated both efficacy and safety.

相反，FDA 實際上指定了他們希望看到的兩種劑量，與 MB-106 試驗中證明療效和安全性的兩種劑量進行比較。

And they're leaving it up to us as the sponsor to ultimately choose between the 190-milligram per meter square and the 230-milligram per meter squared dosing regimens.

他們讓我們作為贊助商，最終在 190 毫克/平方米或 230 毫克/平方米的給藥方案之間做出選擇。

Also, our initial PK analysis that is pharmacokinetic analysis showed that there is no correlation between area under the curve or concentration maximum and the change from the 190 to the 230 dosing regimens or in layman's term, the increase in dosage doesn't appear to increase the amount of drug in circulation.

此外，我們最初的 PK 分析，即藥物動力學分析表明，曲線下面積或濃度最大值與從 190 到 230 的給藥方案的變化之間沒有相關性，或者用外行人的話來說，劑量的增加似乎不會增加循環中的藥物量。

And this corroborates our clinical findings to date as we have seen strong efficacy at both dose levels.

這證實了我們迄今為止的臨床發現，因為我們看到兩種劑量水平都具有強大的功效。

So to be clear, we don't see the optimization process resulting in any increased risk in this trial.

因此需要明確的是，我們沒有看到最佳化過程導致這次試驗的風險增加。

In fact, it's just the opposite.

事實上，情況恰恰相反。

To facilitate the dose selection, the data must be unblinded early, which we believe dramatically reduces risk for our investors.

為了方便選擇劑量，必須儘早揭開數據盲法，我們相信這會大大降低投資人的風險。

Yes, that's absolutely right, Paul.

是的，完全正確，保羅。

Remember, most Phase III approval trials leave investors and prospective big pharma partners in the dark for years until the data can finally be unblinded.

請記住，大多數 III 期審批試驗都會讓投資者和潛在的大型製藥合作夥伴多年處於迷茫之中，直到數據最終被揭開。

Our ability to unblind early because of this adaptive design means we won't have to wonder whether our Phase III trial is tracking with endpoint expectations.

由於這種自適應設計，我們能夠提前揭盲，這意味著我們不必擔心我們的第三階段試驗是否符合終點預期。

And by the way, we're still looking at additional ways to improve early visibility in this trial.

順便說一句，我們仍在尋找其他方法來提高這項試驗的早期可見度。

So stay tuned for additional updates on this.

因此請繼續關注此方面的更多更新。

Now this becomes even more meaningful when you look at the endpoint we need to hit.

現在，當你看到我們需要達到的終點時，這變得更加有意義。

Look, let's face it.

瞧，讓我們面對現實吧。

Biotech is a high-risk business, which is why the potential upside returns can be astronomical.

生物技術是一項高風險的業務，因此其潛在的上行回報可能非常巨大。

In oncology, it's estimated that only about 40% of phase -- 45% of Phase III trials will succeed.

在腫瘤學領域，據估計只有大約 40% 到 45% 的 III 期試驗能夠成功。

And the vast majority of those that fail do so because of a lack of efficacy.

而大多數失敗的原因都是缺乏療效。

That's why it's so critical for investors to understand just how much we have derisked our Phase III trial.

這就是為什麼投資人必須了解我們降低第三階段試驗風險的程度。

The FDA is asking us to compare to one of the few standards of care that is approved for use in second-line patients.

FDA 要求我們將其與少數幾個獲準用於二線患者的治療標準之一進行比較。

It's called high-dose ARA-C, or HiDAC.

它被稱為高劑量 ARA-C，或 HiDAC。

Now this is great news for us because the efficacy of HiDAC in this class of patients is well documented and very consistent with a CR rate of around 17% to 18%.

這對我們來說是個好消息，因為 HiDAC 對這類患者的療效是有據可查的，且 CR 率非常一致，約為 17% 至 18%。

That means the performance of AnnAraC, that's what we call the combination of annamycin plus HiDAC, is almost three times greater than HiDAC alone.

這意味著 AnnAraC（我們所說的 annamycin 和 HiDAC 的組合）的性能幾乎是單獨使用 HiDAC 的三倍。

As a comparison, one of our key opinion leaders in the AML space recently commented that the new drug approvals in AML are justified if the new drug is at least 30% better than the standard of care comparison?

作為比較，我們在 AML 領域的一位關鍵意見領袖最近評論說，如果新藥比標準治療好至少 30%，那麼 AML 新藥批准就是合理的？

Well, by this standard, we are over 280% better.

嗯，以這個標準，我們已經好了 280% 以上。

But there is likely less risk than even this massive disparity in performance suggests.

但實際風險可能比這種巨大的業績差異所暗示的要小。

That's because of how HiDAC was measured in these prior large studies.

這是因為在先前的大型研究中 HiDAC 是如何測量的。

In the MIRROS study, you see on the left, patients were allowed two cycles of treatment in order to reach a CR.

在 MIRROS 研究中，如您在左側所見，患者可以接受兩輪治療才能達到 CR。

And in the CLASSIC I trial, they were allowed even more up to 120 days of treatment before reaching their endpoint.

在 CLASSIC I 試驗中，患者被允許接受長達 120 天的治療才能達到終點。

In contrast, our CRs were accomplished in less than 49 days with just one cycle of treatment.

相較之下，我們僅透過一個治療週期就在不到 49 天的時間內達到了 CR。

What this means is that the performance delta between test and control could be even greater than we're predicting.

這意味著測試和控制之間的效能差異可能比我們預測的還要大。

So now let's look at the potential impact this endpoint could have on the timing of approval.

現在讓我們看看這個終點對批准時間可能產生的潛在影響。

And let me caveat.

請容許我提出警告。

This is not the plan.

這不是計劃。

It's just a look at some potential upside.

這只是對一些潛在優勢的觀察。

We had an investor recently challenge us on our trial design.

最近有一位投資者對我們的試驗設計提出了質疑。

Now he had a decent understanding of statistics and said, if your performance is expected to be so much better than HiDAC, why do you have 330 patients in the total trial?

現在他對統計學有了相當的了解，並說道，如果預計你們的表現會比 HiDAC 好很多，那為什麼整個試驗中有 330 名患者？

Shouldn't you be able to achieve statistical significance with closer to 100 patients?

你不應該能夠透過接近 100 名患者來實現統計意義嗎？

The answer is that this is what big pharma has asked us to do.

答案是，這是大型製藥公司要求我們做的。

In our discussions with prospective partners, we have heard more than once that these players have been burned by buying into a Phase III trial only to end up having it remiss its endpoint because they didn't have sufficient subjects to power the test because the delta between test and control ended up being closer than management estimated.

在與潛在合作夥伴的討論中，我們不只一次聽說，這些參與者因參與第三階段試驗而遭受損失，最終卻因為沒有足夠的受試者來進行測試而導致試驗未能達到終點，因為測試和對照之間的差異最終比管理層估計的更接近。

In essence, small biotech teams facing tight budgets and timelines get lured into overly optimistic assumptions that result in underpowered studies.

實質上，小型生技團隊面臨預算和時間緊張的問題，他們會陷入過於樂觀的假設，從而導致研究動力不足。

Big pharma would much rather buy into a longer, more expensive study that they believe has a higher likelihood of success.

大型製藥公司更願意參與一項他們認為成功可能性較高的、時間更長、成本更高的研究。

And that's what we try to do here.

這正是我們在此嘗試要做的事。

But what happens if our numbers play out closer to what history suggests.

但如果我們的數字更接近歷史預測，會發生什麼事呢？

What if at the unblinding of 90 patients, we're really outperforming HiDAC by 280%.

如果在 90 位病患揭盲時，我們的表現確實比 HiDAC 高出 280%，那會怎麼樣呢？

Well, under those circumstances, assuming drug safety is also in line with our experience to date, it's very likely that our independent data monitoring committee could conclude that continuation of the control arm of the trial would be considered unethical.

好吧，在這種情況下，假設藥物安全性也與我們迄今為止的經驗一致，那麼我們的獨立數據監測委員會很可能會得出結論，繼續進行試驗的對照組將被認為是不道德的。

And at that point, we would likely request a Type A meeting with the FDA to discuss converting Part B of our trial into a smaller single arm, the study designed to complete the safety analysis and satisfy DEI requirements.

此時，我們可能會要求與 FDA 舉行 A 類會議，討論將我們試驗的 B 部分轉換為較小的單組，該研究旨在完成安全性分析並滿足 DEI 要求。

Essentially, it could take a year or more off of the approval time line and virtually eliminate any remaining efficacy-related approval risk.

本質上，它可以將審批時間縮短一年或更長時間，並幾乎消除任何剩餘的與功效相關的審批風險。

Now in no way are we asking investors to plan on this, but we want to make sure you understand how dramatic the upside could be here.

現在我們絕對不會要求投資者為此制定計劃，但我們希望確保您了解這裡的上行潛力有多巨大。

What we are saying is if you want something to worry about regarding Moleculin, it shouldn't be the traditional efficacy risk associated with most Phase III trials.

我們所說的是，如果您想擔心與 Moleculin 有關的事情，那麼它不應該是與大多數 III 期試驗相關的傳統功效風險。

Our biggest focus right now needs to be on recruitment because the pace of recruitment is going to drive our data milestones.

我們現在最大的關注點需要放在招募上，因為招募的步伐將推動我們的數據里程碑。

We are in a race to open sites and start recruiting patients just as quickly as we can to ensure that we get to the interim day readouts that everybody wants to see.

我們正在競相開放站點並儘快開始招募患者，以確保我們能夠獲得每個人都想看到的中期當日數據。

To date, we have 60 sites interested and 17 more sites we're targeting.

到目前為止，已有 60 個站點對我們感興趣，還有 17 個站點是我們的目標站點。

And you can see by this map that this is happening on a global scale.

從這張地圖上你可以看出，這種現象正在全球範圍內發生。

But Paul and I are committed to ensuring these sites are engaged and productive.

但保羅和我致力於確保這些網站的活躍和富有成效。

To that end, we are actively physically visiting any of these sites that we think could be big producers to make sure their facilities and systems are up to the task and that the principal investigators understand the science and the protocol and are truly bought in to the importance of this trial.

為此，我們正在積極實地考察我們認為可能成為大生產商的任何站點，以確保他們的設施和系統能夠勝任這項任務，並且主要研究人員了解科學和協議，並真正認識到這次試驗的重要性。

It takes a lot of effort to meet face-to-face with every one of these investigators.

與每一位調查員面對面會談都需要花費很大的精力。

But we believe it will pay off in terms of delivering the data readouts

但我們相信，在提供數據讀數方面，它將帶來回報

--

--

Hold on.

堅持，稍等。

I know you're going to skip this part.

我知道你會跳過這部分。

But I'm sorry to interrupt.

但很抱歉打擾你。

Look, I got to point out that everybody on this call, what you and Paul did the last few weeks.

聽著，我必須向通話中的每個人指出，你和保羅在過去幾週做了什麼。

I know you weren't going to do it, but look, they believe in annamycin so much, they went into a country at war and another where they're experienced in riots.

我知道你不會這麼做，但你看，他們如此相信安納黴素，他們去了兩個發生戰爭的國家，還去了另一個發生過暴動的國家。

So we're in riots, stranded in Georgia.

因此我們陷入了騷亂，被困在喬治亞州。

Wally and Paul spent two nights in a bomb shelter in key, just to be able to meet the investigators, face-to-face.

沃利和保羅在基韋斯特的防空洞待了兩個晚上，只為能夠與調查人員面對面會面。

They went from there to Tbilisi right in the middle of the riot in the street.

他們從那裡前往第比利斯，正好趕上街頭騷亂。

So I think over the contested presidential election.

所以，我對這場有爭議的總統大選進行了思考。

But I ask the analysts and the people on this line, how many senior management teams do you know that would do this all of their own personal risk to ensure the success of a cancer drug?

但我想問分析師和這條線上的人們，你們知道有多少高階管理團隊願意冒著個人風險來確保抗癌藥物的成功？

Think about it.

想一想。

Sorry, Wally.

對不起，沃利。

Thanks, John.

謝謝，約翰。

Well, the fact is my wife wasn't very happy about it.

事實上我的妻子對此並不太高興。

And look, maybe it was a little extreme, but as you said, John, we believe deeply in annamycin, and we are all committed to doing what has to be done to get this drug approved.

你看，也許這有點極端，但是正如你所說，約翰，我們深信安納黴素，我們都致力於盡一切努力讓這種藥物獲得批准。

This is a fight worth winning, and we believe we're going to win.

這是一場值得打贏的戰鬥，我們相信我們將會勝利。

Now we've been focusing 100% on AML today, but we should never forget that annamycin has potential applications far beyond AML.

今天我們的注意力全部集中在 AML 上，但我們永遠不應忘記，annamycin 的潛在應用遠不止於 AML。

In fact, the growth potential is probably in the range of 20 times that which would come just from AML.

事實上，成長潛力可能達到反洗錢業務成長潛力的 20 倍。

And successful drugs in the AML space are often valued in the billions.

抗反洗錢領域的成功藥物通常價值數十億美元。

So John, let's go back to you and ask you to wrap things up here with a review of the financial situation.

所以約翰，我們回到你這裡並請你總結一下財務狀況。

Sure, Wally.

當然，沃利。

We ended the quarter with $9.4 million in cash on hand, enough to reach into Q1 of 2025, using our fully diluted shares outstanding, which includes the prefunded warrants or market cap is roughly $15.9 million.

截至本季末，我們手頭上有 940 萬美元現金，足以維持到 2025 年第一季度，使用我們完全稀釋的流通股，其中包括預付認股權證或市值約為 1,590 萬美元。

Our stock has about 40,000 shares traded on average each day.

我們的股票每天平均交易約 40,000 股。

So we got to go back to the MIRACLE chart, where we have some key inflection points coming.

因此我們必須回到奇蹟圖表，那裡有一些關鍵的轉折點。

And as Wally said, we're looking to add more.

正如沃利所說，我們希望增加更多內容。

Shown on the scan chart, let's discuss the key milestones in our plan.

依照掃描圖所示，讓我們討論一下計畫中的關鍵里程碑。

First of all, a look for more information on contracting and recruitment of sites later this year.

首先，請留意今年稍後有關承包和招募場地的更多資訊。

And then the first subject treated in MIRACLE should occur in the first quarter of 2025.

MIRACLE 治療的第一個受試者應該出現在 2025 年第一季。

Then we'll have a look at the overall CR rate and recruitment update in the second half of 2025.

然後，讓我們來看看 2025 年下半年的整體 CR 率和招募更新。

This should allow us to interpret the CR rate on possible sets of the trial, north of 20%, 25%, given the historical CR rate of HiDAC, as Wally mentioned, should indicate the efficacy of annamycin as it works, will take us approximately $15 million to get to this point.

這應該使我們能夠解釋試驗中可能的 CR 率，考慮到 HiDAC 的歷史 CR 率，在 20%、25% 以上，正如 Wally 提到的那樣，應該表明 annamycin 的有效性，我們需要大約 1500 萬美元才能達到這一點。

Then the big data readout in mid-2026, interim primary efficacy and safety data on the first 75 to 90 patients, that readout, in my opinion, will really show people the possibility and the risk associated with the success of this trial.

然後，在 2026 年中期，大數據讀數，對前 75 至 90 名患者的中期主要療效和安全性數據，我認為，該讀數將真正向人們展示與該試驗成功相關的可能性和風險。

This should -- I'm sorry, mid 2026 is the interim data readout.

這應該——抱歉，2026 年中期是期中數據讀數。

And then that cascades into a lot of action as we finish Part B, and we started enrollment of MIRACLE 2 for third-line subjects.

然後，當我們完成 B 部分時，這會產生很多行動，我們開始為第三線受試者招募 MIRACLE 2。

And then in 2028, we have the primary efficacy data point for second-line subjects.

然後在 2028 年，我們將獲得二線受試者的主要療效數據點。

And having that final primary efficacy data for those second-line subjects will allow us in the second half of 2028 to begin submission of a rolling NDA for the treatment of relapsed/refractory for accelerated approval on the primary endpoint of CR from this MIRACLE trial.

有了這些二線受試者的最終主要療效數據，我們就能在 2028 年下半年開始提交滾動 NDA，用於治療復發/難治性患者，以獲得此 MIRACLE 試驗主要終點 CR 的加速批准。

So to conclude, as Wally has already described, the MIRACLE trial is unlike any other Phase III trial that I know of, and has substantially derisked and provides many informative key data points along the way.

總而言之，正如 Wally 已經描述的，MIRACLE 試驗不同於我所知道的任何其他 III 期試驗，並且已大大降低了風險並在此過程中提供了許多資訊豐富的關鍵數據點。

And we're looking to improve that visibility, as Wally mentioned.

正如沃利所提到的，我們正在尋求提高這種知名度。

Wally?

沃利？

Yes.

是的。

Thanks, John.

謝謝，約翰。

Before we conclude, let's see if we can address questions from the analyst community.

在結束之前，讓我們看看是否可以回答分析師社群的問題。

Jenene?

詹妮？

Great.

偉大的。

Kevin, can you please open up for Q&A?

凱文，您可以開放時間進行問答嗎？

(Operator Instructions) Jonathan Aschoff, ROTH.

（操作員指示）Jonathan Aschoff，ROTH。

I have four questions for you.

我有四個問題想問您。

The first is you last -- you had reported a median OS of greater than or equal to six months in 10 second-line patients, but I don't see an updated number there.

第一個是您最後報告的——在 10 名二線患者中，中位 OS 大於或等於六個月，但我沒有看到更新的數字。

Is there any update to that median OS currently?

目前該中位作業系統有任何更新嗎？

Yeah.

是的。

So Paul, do you want to -- just re-summarize what's in the swimmers chart because we've made a lot of progress since that last report.

那麼保羅，你想——重新總結游泳者圖表中的內容嗎，因為自上次報告以來我們已經取得了很大進展。

Our overall median survival now is over seven months in this population, which, again, is far greater by almost a factor of two than what the literature would suggest -- would predict

目前，該族群的整體平均存活期超過 7 個月，比文獻建議的存活期高出近兩倍。

--

--

Yeah.

是的。

Yeah.

是的。

It's a highly conservative trial, I think, given what you have to hurdle.

我認為，考慮到必須克服的障礙，這是一次高度保守的試驗。

I think it's well designed, the MIRACLE trial.

我認為 MIRACLE 試驗設計得非常好。

Anyway, so why was MIRACLE enrollment bumped?

無論如何，為什麼 MIRACLE 入學人數會增加呢？

And maybe you've explained this before in a different form, from 40 to 45.

也許您之前已經用不同的形式解釋過這一點，從 40 到 45。

The first look, you said 75 before, but now you're saying -- like the 10-Q says 90, the PR say 75 to 90.

乍一看，您之前說的是 75，但現在您說 - 就像 10-Q 說的是 90，PR 說的是 75 到 90。

And then I had in a prior note that after that, when you determine the optimal dose, I had 120.

然後我在之前的記錄中提到，在那之後，當你確定最佳劑量時，我的劑量是 120。

And 120 is now 240 to be enrolled.

現在需要入學的人數從 120 人增加到 240 人。

I'm just kind of curious what specifically led to that increase at all three of those looks.

我只是有點好奇究竟是什麼導致了這三種外觀的增加。

Yeah.

是的。

There's -- I think there's several factors at work here.

我認為這裡有幾個因素在起作用。

Let me start backwards and say that the issue about 120 versus 240, I think, has to do with the specific paragraph descriptions.

讓我從後往前說，我認為 120 與 240 的問題與具體的段落描述有關。

It's always been 120 per treatment arm, but we're always afraid that people will read that as 120 in total.

每個治療組一直都是 120 個，但我們總是擔心人們會把它讀成總共 120 個。

So we've tended to default to describing it as 240.

因此我們傾向於默認將其描述為 240。

So we're not -- we have an increased -- we haven't doubled the size of the trial.

因此，我們沒有擴大試驗規模，也沒有將試驗規模擴大一倍。

We've just made sure that people aren't being misled between 120 per treatment arm and 240 in total for the -- for Part B. So that's what's going on there.

我們只是確保人們不會被每個治療組 120 人和 B 部分總共 240 人之間誤導。

As it relates to the number in Part A, it has been moving around.

由於它與 A 部分中的數字相關，因此它一直在移動。

And part of what's been moving it around is optimizing statistics.

其中部分工作就是優化統計資料。

One of the things that -- I mean, the reality is in order to -- I mean, you know this, Jonathan, global clinical trials like this are extremely complex.

其中一件事——我的意思是，現實情況是——我的意思是，喬納森，你知道，像這樣的全球臨床試驗極其複雜。

When you got 60 to 90 treatment sites and on six different continents, it gets complicated fast.

當你在六大洲有 60 到 90 個治療點時，事情很快就會變得複雜。

And so you can get buried in all the startup requirements because every one of those hospitals has to have a contract negotiated.

因此，您可能會陷入所有啟動要求的泥潭中，因為每家醫院都必須協商合約。

There's ethics review boards.

有道德審查委員會。

It gets -- there's a lot of lead time.

它需要很長的準備時間。

And so none of those processes can happen until you have -- until you put a stake in the ground, say here's our protocol.

因此，除非你奠定基礎，即這是我們的協議，否則所有這些過程都無法進行。

Well, the biostatistics analysis goes on and on and on for a long time because there's a lot of refinement in what-if analysis.

嗯，生物統計學分析需要持續很長時間，因為假設分析中有很多細化步驟。

But we didn't want to wait for all of that what-if analysis in order to get started -- to get the contracting and ethics reviews started.

但我們不想等待所有的假設分析完成後才開始簽訂合約和進行道德審查。

And so we put a stake in the ground and said, this is good enough for now, but we'll continue to refine the actual numbers of the trial as we get closer to the starting line.

因此，我們打下了基礎並表示，目前這已經足夠好了，但隨著我們越來越接近起跑線，我們會繼續優化試驗的實際數字。

So -- and that's still -- that work is still ongoing.

所以 — — 這項工作仍在進行中。

So we could have some minor tweaks as this gets closer to the start.

因此，當事情開始接近尾聲時，我們可能會進行一些細微的調整。

But if anything right now, and we kind of embedded this in the presentation, we're expecting that if anything, we've got -- we may have some opportunities for even earlier visibility than is currently expected.

但如果現在有什麼事情發生，而且我們將其嵌入到簡報中，我們預計，如果有的話，我們可能會有機會比目前預期的更早獲得可見性。

So just stay tuned as we get that completely refined.

請繼續關注，我們會對其進行徹底的完善。

Yeah, it's definitely wise to do everything you can to not swing and miss at that accelerated approval opportunity.

是的，盡一切努力避免錯過加速審批機會絕對是明智之舉。

It's absolutely a lot of lead times more than waiting for 240.

這絕對比等待 240 多得多的準備時間。

The last one is -- I mean, the third one is a little bit picky.

最後一個——我的意思是，第三個有點挑剔。

Is the 3Q 24 R&D, is that a new run rate?

第三季的 24 項研發是否是新的運作率？

Or does that include a lumpy slug of annamycin production?

或者這是否包括大量 annamycin 的產生？

I'm going to let that one for John.

我要把這個留給約翰。

Yeah.

是的。

Yeah.

是的。

Sorry to jump in there.

很抱歉打擾您。

But yeah, that was a slug of annamycin production as well as some sponsored research really accelerated at MD Anderson.

但是的，這是 annamycin 生產的一個重大突破，而 MD Anderson 的一些贊助研究也確實加速了。

We've had some additional programs going on there.

我們在那裡正在進行一些額外的項目。

So we accelerated some sponsored research there as well.

因此我們也加速了一些贊助研究。

Okay.

好的。

And John, again, what's the -- what is the number of shares from prepaid warrants that's not in your 3 million November 1 share count?

約翰，再問一下，預付認股權證中的股票數量不包含在 11 月 1 日的 300 萬股股票數量中，是多少？

Roughly 2 million.

大約200萬。

And I was kind of curious -- roughly 2 million.

我有點好奇——大約200萬。

Okay.

好的。

And then the last part of that is why is that 3 million November 1 count so much lower than the average weighted for the third quarter of 3 points?

最後一部分是，為什麼 11 月 1 日的 300 萬分比第三季 3 分的平均加權數低這麼多？

Well, because the warrants that we issued in August -- as part of the August deal are now above water.

嗯，因為我們在八月發行的認股權證——作為八月交易的一部分，現在已經超出了水位。

And so they -- now the warrants count in a fully diluted basis.

所以他們 — — 現在認股權證是按完全稀釋的基礎計算的。

(Operator Instructions) Jason McCarthy, Maxim Group.

（操作員指示）Jason McCarthy，Maxim Group。

Yeah.

是的。

I was just wondering how much do you expect the Phase III to cost?

我只是想知道您預計第三階段的成本是多少？

John, do you want to tackle that?

約翰，你想解決這個問題嗎？

I was afraid you're going to do that.

我擔心你會這麼做。

Well, as Wally mentioned -- what Wally mentioned, even going into the -- the number of sites you need for recruitment, you really have to start off with the plan and keep refining it.

嗯，正如沃利提到的那樣——沃利提到的那樣，即使考慮到——招聘所需的站點數量，你確實必須從計劃開始並不斷完善它。

As you saw on the chart, one of the key things into the cost of the trial is where are we performing in the trial.

正如您在圖表上看到的，試驗成本的關鍵因素之一是我們在試驗中的表現。

Per patient cost in the US are 10x or more greater per patient, which you have to pay the institution in which you have in Eastern and Western Europe -- I mean, Western Asia -- Eastern Europe, Western Asia.

美國每位患者的費用比東歐和西歐（我是說西亞）的醫療機構高出 10 倍或更多。

I would say a good run rate is essentially what I said as stated earlier, you're talking about $50 million per about every three quarters.

我想說，良好的運行率基本上就是我之前所說的，每三個季度大約 5000 萬美元。

You have some lumps in there for annamycin production.

您在那裡有一些用於生產 annamycin 的塊狀物。

And so you just take that to 2028, but if we're able to shorten it, as Wally mentioned, they will have a huge impact.

所以你只能把它帶到 2028 年，但如果我們能夠縮短它，正如沃利所提到的那樣，它們將產生巨大的影響。

So we're refining those numbers as we refine the sites and what areas we're going to.

因此，我們在優化網站和要去的地區時也在優化這些數字。

You'll note -- we do have South Korea on that map, but really not participating in a lot of sites in the Pacific Rim, really helps the budget from a standpoint of having CRAs in that area and drug inventory in that area as well.

您會注意到 - 我們確實在地圖上有韓國，但實際上並沒有參與環太平洋地區的許多站點，從在該地區擁有 CRA 和藥品庫存的角度來看，這確實有助於預算。

So more visibility as we move forward.

因此，隨著我們不斷前進，可見性會更高。

Got it.

知道了。

And then just as far as the STS program, so that's likely final data in the first half '25, moving to a pivotal after.

然後就 STS 計劃而言，這很可能是 25 年上半年的最終數據，之後將進入關鍵階段。

But is this something you guys would look forward to doing your own or seek a partner?

但這是你們期待自己做或尋求夥伴會做的事嗎？

So we've really committed to the notion that we would like to find a partner for that project.

因此，我們確實致力於為該專案尋找合作夥伴。

Obviously, there's enough cost associated with the MIRACLE trial that -- that's where our focus needs to be in terms of our internal resources.

顯然，MIRACLE 試驗的成本已經足夠高了，因此我們需要將內部資源重點放在這上面。

So we basically said, look, any other major undertakings like an STS pivotal trial, we're going to want to work with an outside funding source, maybe in that case, an investigator-sponsored trial, that kind of thing.

所以我們基本上說，看，任何其他重大項目，例如 STS 關鍵試驗，我們都希望與外部資金來源合作，也許在那種情況下，是由研究者贊助的試驗，諸如此類。

Vernon Bernardino, H.C. Wainwright.

伯納迪諾，H.C.溫賴特。

Just -- you've never mentioned this before, but I was wondering if you have pursued or perhaps intend to pursue discussion with the FDA on a special protocol assessment for the MIRACLE trial.

只是——您之前從未提到過這一點，但我想知道您是否已經或打算與 FDA 討論 MIRACLE 試驗的特殊方案評估。

So we've had a number of discussions about that.

因此我們就此進行了多次討論。

But let me hand this over to Paul to talk about our present thinking about special protocol assessments.

但是，讓我把這個主題交給保羅，讓他談談我們目前對特殊協議評估的想法。

Very insightful.

非常有見地。

And when we went to the Phase I/II meeting with FDA, we broached the subject should we submit a protocol for a special protocol assessment.

當我們與 FDA 進行 I/II 期會議時，我們提出了是否應該提交特殊方案評估方案的議題。

And they advised not to do that.

他們建議不要這樣做。

It was a very amicable meeting, and they advise not to do it because it takes time.

這是一次非常友好的會議，他們建議不要這樣做，因為這需要時間。

You have to create the protocol, submit it.

您必須創建協議並提交它。

There's a review period, discussion period.

有一個審查期和討論期。

It adds many months.

它增加了很多月份。

And they said they would be more than happy to review it, but they recommended not doing it because at the end of the meeting, we were all in agreement there were no contentious issues.

他們表示非常樂意審查該報告，但建議不要這樣做，因為會議結束時，我們都一致認為不存在有爭議的問題。

So the thought was, why delaying things for many months when we're in full agreement?

因此我們的想法是，既然我們已經完全同意，為何要拖延數月呢？

I see.

我懂了。

So that's very positive

這是非常積極的

--

--

There's also a factor, Vernon, and you've probably run into this before, but it tends to tie your hands a little bit because what -- in order for an SPA to be worth anything to have any real intrinsic value, you cannot deviate from the strict confines of the protocol that's agreed to in that letter.

還有一個因素，弗農，你可能以前遇到過這個問題，但它往往會束縛你的手腳，因為——為了使 SPA 具有任何真正的內在價值，你不能偏離那封信中同意的協議的嚴格限制。

And so the point Paul was really making was there's a lot of additional delay and lead time in to get to that.

所以保羅真正想說的是，要實現這一目標還需要很多額外的延遲和準備時間。

And then your hands are kind of tied because essentially, anything you want to change in the future negates that SPA and it's like starting over again.

然後你就束手無策了，因為本質上，你將來想要改變的任何事情都會否定該 SPA，就像重新開始一樣。

So there are circumstances where an SPA is probably in the very best interest of the company to protect themselves.

因此在某些情況下，SPA 可能最符合公司的利益，並且可以保護公司本身安全。

But like Paul said, we sort of feel like we've got the FDA on our side here in terms of the trial design and how to get to approval.

但就像保羅所說的那樣，我們覺得在試驗設計和如何獲得批准方面，FDA 是站在我們這邊的。

And so it just did not appear to be worth both the lead time.

因此，這似乎不值得花費預先準備的時間。

And then the risk that if you want to tweak the protocol along the way, you've got a problem.

然後，如果你想在過程中調整協議，那麼就會有問題。

We reached the end of our question-and-answer session.

我們的問答環節已經結束。

I'd like to turn the floor back over for any further or closing comments.

我想將發言權轉回給大家，以便大家可以發表進一步的評論或結束語。

Well, I appreciate everybody making time for an update on Moleculin.

好吧，我感謝大家花時間關注 Moleculin 的最新消息。

I'd just like to leave you with this, AML drugs that are close to approval have consistently been valued in the billions of dollars.

我只想告訴你們這一點，即將獲得批准的 AML 藥物的價值一直高達數十億美元。

And we believe the only rational reasons to be bearish about an asset like annamycin that's in Phase III are that, A, you doubt the ability to hit the end point; B, you doubt the likelihood of approval if that endpoint is hit; or C, you doubt the marketability of the drug once it's approved.

我們認為，對像 annamycin 這樣處於第三階段的資產持悲觀看法的唯一合理理由是：A，你懷疑其能否達到終點； B，您懷疑如果達到該終點，獲得批准的可能性；或 C，您懷疑該藥物一旦獲得批准，其適銷性。

While we've shown you the data that explains why we believe with a very high degree of confidence that we will hit the endpoint of this trial.

我們向您展示了數據，解釋了為什麼我們非常有信心地相信我們將完成這次試驗。

And we've explained that this is the endpoint that the FDA has requested for approval.

我們已經解釋過，這是 FDA 要求批准的終點。

And we have KOLs on record saying that just a fraction of our expected performance should be sufficient for approval.

而且我們有 KOL 記錄表示，只需達到我們預期表現的一小部分就足以獲得批准。

And finally, I can tell you without reservation that every single investigator we've met with, and we're now well into the dozens has agreed that annamycin has the potential to fill a desperate unmet need for AML patients and to be clear, they've all said they would expect to use it extensively in their practice.

最後，我可以毫無保留地告訴你們，我們所見過的每一位研究人員，現在已有數十位研究人員同意，安那黴素有可能滿足 AML 患者迫切的未滿足的需求，而且明確地說，他們都表示希望在實踐中廣泛使用它。

We simply need to execute on our strategy, and that's exactly what we're doing.

我們只需要執行我們的策略，而這正是我們正在做的事情。

I can't wait for the next update.

我等不及要看下一次更新了。

In the meantime, have a great week.

同時，祝您有個愉快的一周。

Thank you.

謝謝。

That does conclude today's teleconference and webcast.

今天的電話會議和網路直播到此結束。

You may disconnect your lines at this time and have a wonderful day.

此時您可以斷開您的線路並享受美好的一天。

We thank you for your participation today.

我們感謝您今天的參與。