Moleculin Biotech Inc (MBRX) 2025 Q1 法說會逐字稿

Good morning. Welcome to the Moleculin Biotech 1st quarter 2025 update Conference Call and Webcast. Question and answer session will follow the formal presentation. As a reminder this conference is being recorded. It is now my pleasure to turn the call over to your host Jenene Thomas, Investor relations. Please go ahead, Jenene.

早安.歡迎參加 Moleculin Biotech 2025 年第一季更新電話會議和網路廣播。正式演講結束後將進行問答環節。提醒一下，本次會議正在錄製中。現在我很高興將電話轉給主持人、投資者關係部 Jenene Thomas。請繼續，詹妮娜。

Thank you, Robin. Good morning, 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. 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 report Moleculin filed 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. 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 of verified in any information obtained from a third-party source. Any data to discuss regarding clinical trials and progress are considered preliminary and subject to change. So, joining us on today's call from Moleculin's leadership team are Walter Klemp, Chairman and Chief Executive Officer; Doctor John Paul Waymack, Senior Chief Medical Officer; and Jonathan Foster, Executive Vice President and Chief Financial Officer. I'd now like to turn the call over to Walter Klemp. Well, Wally please proceed.

謝謝你，羅賓。大家早安。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。這些是前瞻性陳述，涉及風險和不確定性。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條款並基於 Moleculin 當前的預期做出的，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。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。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查閱。我們鼓勵您仔細閱讀這些文件。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。儘管本公司認為截至本簡報發布之日這些第三方來源是可靠的，但它並未獨立驗證，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，也不對任何獨立來源是否已驗證作出任何陳述。任何有關臨床試驗和進展的討論數據都被視為初步數據，可能會發生變化。因此，參加今天 Moleculin 領導團隊電話會議的有董事長兼首席執行官 Walter Klemp；高級首席醫療官 John Paul Waymack 醫生；以及執行副總裁兼首席財務官喬納森·福斯特 (Jonathan Foster)。現在我想把電話轉給 Walter Klemp。好吧，沃利，請繼續。

Thanks, Janine. Hello and welcome to our First Quarter Earnings Conference Call. For most of our investors, the focus is on the Phase 3 MIRACLE trial studying Annamycin for the treatment of relapsed and refractory acute myeloid leukemia. And with good reason, this trial has now officially started with the first patient already treated and more on the way. In total, we now have 38 sites selected worldwide between the US, Europe, Middle East and North Africa. We just announced this week that we also received complete sign-off from the European Medicines Agency for all 9 countries that we wanted to open in the EU. That was one of the longest lead time items for getting the EU up and running, so it was a major milestone and a real show of support from the EMA for our trial design and our objectives.

謝謝，珍妮。您好，歡迎參加我們的第一季財報電話會議。對於我們的大多數投資者來說，重點是研究 Annamycin 治療復發和難治性急性髓系白血病的 3 期 MIRACLE 試驗。這項試驗現已正式啟動，第一位患者已經接受治療，並且還有更多患者即將接受治療，這是有充分理由的。總體而言，我們目前在美國、歐洲、中東和北非等全球範圍內選定了 38 個站點。我們本週剛剛宣布，我們還獲得了歐洲藥品管理局對我們想要在歐盟開放的所有 9 個國家的完整批准。這是歐盟啟動和運行所需時間最長的計畫之一，因此它是一個重要的里程碑，也是 EMA 對我們的試驗設計和目標的真正支持。

Also, the World Health Organization has officially recognized a new generic drug name for Annamycin, which may now be referred to in literature as Naxtarubicin. This was an important first step in actually launching Annamycin once it receives new drug approval. And compared with some of the unpronounceable crazy drug names out there, we're really pleased with Naxtarubicin, especially since it sounds a lot like the next Rubisin, which really plays into the next generation positioning of Annamycin. You should expect to see us using both names together until such time as we establish an FDA approved brand name, which is the next step in positioning the drug for launch. And we also announced some additional patent protection for Annamycin. Even though we already had composition of matter protection extending into at least 2040, these additional patents just continue to build a wider fence of protection around our core asset.

此外，世界衛生組織已正式認可了 Annamycin 的新通用藥物名稱，現在在文獻中可以將其稱為 Naxtarubicin。這是 Annamycin 獲得新藥批准後實際上市的重要第一步。與一些難以發音的瘋狂藥物名稱相比，我們對 Naxtarubicin 感到非常滿意，特別是因為它聽起來很像下一代 Rubisin，這確實符合 Annamycin 的下一代定位。在我們確定 FDA 批准的品牌名稱之前，您應該會看到我們同時使用這兩個名稱，這是定位藥物上市的下一步。我們也宣布了對 Annamycin 的一些額外專利保護。儘管我們已經將物質成分保護延長至至少 2040 年，但這些額外的專利只是繼續在我們的核心資產周圍建造更廣泛的保護屏障。

We should also be announcing a date for the presentation of the final data from our MD 107 clinical trial using Annamycin to treat advanced soft tissue sarcoma. Although the preliminary numbers were impressive, we think the final data are really going to turn some heads. So, please look for an announcement on this in the coming weeks.

我們還應該宣布使用 Annamycin 治療晚期軟組織肉瘤的 MD 107 臨床試驗的最終數據的發布日期。儘管初步數據令人印象深刻，但我們認為最終數據確實會引起一些人的注意。因此，請在未來幾週內關注有關此事的公告。

Now this graphic gives you a better perspective on the status of our site selection and approval process for the MIRACLE trial. Compared with the version from our last earnings call, we now have the great majority of countries and sites approved from a regulatory standpoint, and now we're just wrapping up hospital contracts and local ethics approvals. Just to be clear though, the most important milestone for us coming up will be the unblinding of the 1st 45 patients. A lot of eyes will be on us for this data point, as it should tell the world definitively that we are likely headed for new drug approval. With that said, what you see here is what gives us so much confidence that we expect to have those 1st 45 patients treated before the end of this year.

現在，這張圖表可以讓您更了解 MIRACLE 試驗的選址和審批流程的現況。與我們上次收益電話會議上的版本相比，從監管角度來看，我們現在已經獲得了絕大多數國家和地點的批准，現在我們正忙於完成醫院合約和當地倫理審批。但需要明確的是，我們即將迎來的最重要的里程碑是揭開前 45 名患者的神秘面紗。許多人的目光都將集中在這個數據點上，因為它應該明確地告訴全世界，我們很可能即將獲得新藥批准。話雖如此，您在這裡看到的情況給了我們很大的信心，我們預計在今年年底之前將對首批 45 名患者進行治療。

To drive this home just averaging one patient per site for the remainder of the year gets us there and given the enthusiasm that we've seen from these sites, we think we're going to outpace that rate. Now look, we know a lot of investors think that Annamycin is the entire ball game for us. And to be sure, it's where most of the attention should be focused because it's so close to NDA submission. But we do have two other very exciting technologies, and one of them is WP1066, our lead STAT3 inhibitor. Don't forget that WP1066 has already shown activity in the treatment of brain tumors, and that was with a very inefficient form of drug delivery. Well, now WP1066 is in another investigator sponsored clinical trial this time in combination with radiation at Northwestern University. And since we announced this trial in September of last year, we've already recruited 7 patients. That's nearly a patient per month for just one site. So this is moving quickly.

為了實現這一目標，我們只需在今年剩餘時間內平均每個站點接待一名患者即可，並且考慮到我們從這些站點看到的熱情，我們認為我們將超過這個速度。現在看，我們知道很多投資者認為 Annamycin 對我們來說就是一切。可以肯定的是，這是人們應該集中大部分注意力的地方，因為它距離 NDA 提交非常近。但我們確實還有另外兩項非常令人興奮的技術，其中之一就是 WP1066，也是我們主要的 STAT3 抑制劑。別忘了，WP1066 已經顯示出治療腦腫瘤的活性，而且是採用一種非常低效的藥物傳遞方式。現在，WP1066 正在進行另一項由研究者發起的臨床試驗，這次是與西北大學的放射療法相結合進行的。自去年 9 月宣布這項試驗以來，我們已經招募了 7 名患者。這幾乎意味著僅在一個站點每月就有一名患者。所以進展很快。

Now this is still with the existing oral delivery, which we know isn't optimal, and we're collaborating with Emory University on the development of an IV delivery for 1066, which we think could significantly improve its activity. So, we'll keep you updated as more developments occur here. Well, that gives you a high-level overview of recent events. So now let me hand things over to Doctor Paul Waymack, our Senior Chief Medical Officer, to give you a few more insights into our clinical activity. Paul?

目前，我們仍然採用現有的口服給藥方式，我們知道這種方式並不是最佳的，我們正在與埃默里大學合作開發 1066 的靜脈給藥方式，我們認為這種方式可以顯著提高其活性。因此，我們會及時向您通報更多進展。好吧，這為您提供了最近事件的總體概述。現在，讓我將時間交給我們的高級首席醫療官 Paul Waymack 醫生，以便讓您更了解我們的臨床活動。保羅？

Thanks, Wally. Before I speak about the MIRACLE trial, let's catch up on our MB-106 phase two trial, which had essentially the same inclusion and exclusion criteria, plus the same treatment regimen for patients as MIRACLE. Except we treated some first line plus some third line and beyond subjects in MB-106. Our first patient who did not receive a bone marrow transplant but did receive a complete remission finally relapsed after over 600 days. While we are disappointed with the subject, it must be said that achieving an almost 2-year complete remission for a 78-year-old following 17 cycles of a Venetoclax regimen. It's remarkable given the recent literature which documents the dismal median overall survival. For Venetoclax regimen failures, which have a median overall survival of less than 3 months regardless of further treatments. Our durability for MB-106 is still developing as the final three subjects are maintaining their complete remission. You can see on this chart that receiving a bone marrow transplant definitely correlates with better durability. And if these 3 keep moving to the right, the median durability for this trial should eventually be even with subject to durability, that is roughly 400 days.

謝謝，沃利。在我談論 MIRACLE 試驗之前，讓我們先來了解一下 MB-106 第二階段試驗，該試驗的納入和排除標準基本上與 MIRACLE 相同，並且患者的治療方案也相同。除了我們在 MB-106 中治療了一些一線以及一些三線及以上的科目。我們的第一位患者沒有接受骨髓移植但獲得了完全緩解，但最終在 600 多天後復發。雖然我們對這個主題感到失望，但必須要說的是，經過 17 個週期的 Venetoclax 療法治療後，一名 78 歲的老人獲得了近 2 年的完全緩解。鑑於最近的文獻記載了慘淡的整體存活率中位數，這一點非常引人注目。對於 Venetoclax 方案失敗的患者，無論是否接受進一步治療，平均總存活期均少於 3 個月。由於最後三名受試者保持了完全緩解，因此 MB-106 的耐久性仍在發展中。您可以從這張圖表中看到，接受骨髓移植肯定與更好的耐久性有關。如果這 3 個繼續向右移動，則該試驗的中位耐久性最終應該與受試耐久性相等，即約 400 天。

Now moving on to the MIRACLE trial. We will only treat initial refractory relapsed AML subjects. That is, this is a 2nd line therapy study. Where Annamycin in combination with Cytarabine will be delivered on a 5 plus 3 days basis. Compared to just Cytarabine plus placebo. As Wally mentioned, recruitment and treatment of subjects is already underway in Ukraine, and we expect the initial readout of safety and efficacy data on the 1st 45 subjects around the end of 2025. On May 12, we announced that the European Medicines Agency, that is the EMA, they approved our clinical trial application to conduct their MIRACLE trial in all 9 countries we submitted to in the EU. We received final reports of acceptable for Belgium, Czechia, France, Germany, Italy, Lithuania, Poland, Romania, and Spain. These approvals are under the condition that we submit results of appropriate non-clinical GLP studies before initiating the phase 3 portion, that is the part B of the MIRACLE study. Combined with individual country committees and ethics approval for these 9 countries in the EU, allows us to proceed in enrolling subjects in these countries.

現在繼續進行 MIRACLE 試驗。我們僅治療初次出現難治性復發的 AML 患者。也就是說，這是一項二線治療研究。其中 Annamycin 與阿糖胞苷的組合將在 5 天加 3 天的基礎上給藥。與僅使用阿糖胞苷加安慰劑相比。正如沃利所提到的，烏克蘭已經在進行受試者的招募和治療，我們預計將在 2025 年底左右初步讀取前 45 名受試者的安全性和有效性數據。5 月 12 日，我們宣布歐洲藥品管理局（即 EMA）批准了我們的臨床試驗申請，將在我們提交的歐盟所有 9 個國家進行 MIRACLE 試驗。我們收到了比利時、捷克、法國、德國、義大利、立陶宛、波蘭、羅馬尼亞和西班牙可接受的最終報告。這些核准的條件是，我們在啟動第 3 階段（即 MIRACLE 研究的 B 部分）之前提交適當的非臨床 GLP 研究的結果。結合各國委員會和歐盟這 9 個國家的倫理批准，我們可以在這些國家進行受試者招募工作。

Also, in November 2024, we amended our existing US IND by submitting the MIRACLE trial protocol, which allows for dosing of US AML patients above the lifetime maximum allowable dose for currently prescribed anthracyclines. Since then, we received FDA feedback and guidance on that amendment. This feedback allowed a reduction in the number of subjects to be enrolled in Part B of the Phase 3 Pivotal protocol to 222 patients. And obviously any reduction in recruitment numbers helps to shorten the time for completion of the trial. FDA made a number of other requests related to our protocol. These requested changes focused mainly on safety and subject monitoring, clinical pharmacology, and inclusion and exclusion criteria. None of the requests resulted in significant alterations in the overall trial design or the dosing of Annamycin. Our last response to FDA was submitted on April 18, 2025. And we have not yet received follow up communication since that time. We are therefore now proceeding with this amended MIRACLE trial protocol in the US. As is typical with large pivotal phase 3 global clinical trials at their onset. There are minor differences between the US and EU protocols due to FDA and EMA requests. However, we do not view these as a barrier to successfully completing the study. And we are now working to harmonize the protocols into a single global version.

此外，2024 年 11 月，我們透過提交 MIRACLE 試驗方案修改了現有的美國 IND，該方案允許對美國 AML 患者使用目前處方的蒽環類藥物的終生最大允許劑量以上劑量的藥物。從那時起，我們收到了 FDA 對該修正案的回饋和指導。此回饋使得參與第 3 階段關鍵方案 B 部分的受試者數量減少至 222 名患者。顯然，招募人數的任何減少都有助於縮短完成試驗的時間。FDA 提出了一些與我們的協議相關的其他要求。這些要求的改變主要集中在安全性和受試者監測、臨床藥理學以及納入和排除標準。這些請求均未導致整體試驗設計或 Annamycin 劑量發生重大改變。我們對 FDA 的最後回覆是在 2025 年 4 月 18 日提交的。從那時起我們還沒有收到後續訊息。因此，我們目前正在美國推進這項修訂後的 MIRACLE 試驗方案。正如大型關鍵性 3 期全球臨床試驗開始時的典型情況一樣。由於 FDA 和 EMA 的要求，美國和歐盟協議之間存在細微差別。然而，我們並不認為這些是成功完成研究的障礙。我們現在正致力於將這些協議統一為一個全球版本。

Regarding our newly initiated phase 3 study, it was designed after an end of phase 1-2 meeting with FDA. It is to be a randomized study comparing the dosing regimen with which we had great success in our MB-106 study, that is Annamycin plus high-dose Cytarabine with a control arm of placebo plus high-dose Cytarabine. We chose this design because the FDA encouraged it, and because two recent large randomized clinical trials in refractory and relapsed AML patients, that is the Mirros and Classic 1 clinical trials. Used it and both achieved approximately a 17.5% complete remission rate, among patients randomized to receive high dose Cytarabine plus placebo. To that end, we can expect we will need for our Annamycin plus high dose Cytarabine treatment arm to beat a 17.5% complete response rate to a statistically significant degree for a drug to be approved by FDA for marketing.

關於我們新啟動的 3 期研究，它是在與 FDA 進行 1-2 期會議結束後設計的。這是一項隨機研究，比較了我們在 MB-106 研究中取得巨大成功的給藥方案，即 Annamycin 加高劑量阿糖胞苷，對照組為安慰劑加高劑量阿糖胞苷。我們選擇這種設計是因為 FDA 鼓勵這種設計，並且最近在難治性和復發性 AML 患者中進行了兩項大型隨機臨床試驗，即 Mirros 和 Classic 1 臨床試驗。使用該藥物，在隨機接受高劑量阿糖胞苷加安慰劑的患者中，均實現了約 17.5% 的完全緩解率。為此，我們可以預期，我們的 Annamycin 加高劑量阿糖胞苷治療組的完全緩解率需要達到 17.5%，才能在統計上顯著地超過 FDA 批准上市的水平。

But as a reminder, in our MB-106 study, this combination of Annamycin plus high dose Cytarabine achieved a 50% complete remission rate. The primary efficacy endpoint for this study will be the rate of complete remission of the leukemia at approximately day 35. During part A of our study, we will have two different Annamycin treatment arms, a 190 mg per meter square treatment arm, and a 230 mg per meter square treatment arm. There will be an unblinding of the data in Part A after the 1st 45 patients have completed their efficacy analysis. And a second unblinding after between 75 and 90 patients have completed their efficacy analysis. These interim looks at the data are in part to determine which of the two Annamycin dosing regimens will be taken to completion of the study. In Part B of the study, we will continue enrolling patients, but we will then randomize in a 1:1 ratio, the placebo plus Cytarabine treatment arm against whichever the two dosing regimens of Annamycin was found to be superior plus the Cytarabine treatment arm.

但需要提醒的是，在我們的 MB-106 研究中，Annamycin 加高劑量阿糖胞苷的組合實現了 50% 的完全緩解率。本研究的主要療效終點是大約第 35 天白血病完全緩解率。在我們研究的 A 部分中，我們將有兩個不同的 Annamycin 治療組，一個是每平方公尺 190 毫克的治療組，另一個是每平方公尺 230 毫克的治療組。前 45 名患者完成療效分析後，將揭開 A 部分數據的盲法。在 75 至 90 名患者完成療效分析後進行第二次揭盲。這些中期資料觀察的部分目的是為了確定採用哪一種 Annamycin 給藥方案來完成研究。在研究的 B 部分，我們將繼續招募患者，但我們將以 1:1 的比例隨機分配安慰劑加阿糖胞苷治療組與兩種經證實更優的 Annamycin 給藥方案加阿糖胞苷治療組。

Finally, as Wally mentioned, we intend to release the final data readout on MD-107, where we treated advanced soft tissue sarcomas, which had metastasized to the lung with Annamycin as monotherapy. Most subjects were treated well above the lifetime maximum anthracycline dose. And yet after reviewing all the cardiac safety data, our expert noted that he saw no signs of study related drug induced cardiotoxicity. We are excited about the results of these trials, obviously. Now, I'll turn it over to Jon Foster, our Executive Vice President and CFO, Jon.

最後，正如沃利所提到的，我們打算發布 MD-107 的最終數據讀數，我們使用 Annamycin 作為單一療法治療已轉移到肺部的晚期軟組織肉瘤。大多數受試者接受的治療劑量遠高於其一生中最大蒽環類藥物劑量。然而，在審查了所有心臟安全數據後，我們的專家指出，他沒有發現與研究相關的藥物引起心臟毒性的跡象。顯然，我們對這些試驗的結果感到非常興奮。現在，我將把發言權交給我們的執行副總裁兼財務長喬恩‧福斯特 (Jon Foster)。

Thanks, Paul. We ended the quarter with about $8 million with cash on hand. They should run our operations into the 3rd quarter of this year. To get us well into the first quarter of 2026, we will need to raise approximately $15 million. Now we expect this amount will get us beyond the initial 45 subject data readout, supporting our efficacy rates with the additional 30 subjects receiving Annamycin or Naxtarubicin. And also by then we should have a total of 75 to 90 subjects recruited. Moving us closer to the second data readout in the first half of 2026. Our market cap is up to over $14 million with 14.1 million shares outstanding. Our trading volume is healthy with a 3-month trading volume of almost 6 million shares per day. It is spiky. We had a healthy volume of about 2.4 million shares traded this past Monday with the EU news that Wally and Paul just mentioned.

謝謝，保羅。本季結束時，我們手頭上有約 800 萬美元現金。他們應該將我們的業務運作到今年第三季。為了順利進入 2026 年第一季度，我們需要籌集約 1,500 萬美元。現在我們預計這個數量將使我們的數據讀數超出最初的 45 個受試者，並支持另外 30 個接受 Annamycin 或 Naxtarubicin 治療的受試者的療效率。到那時，我們總共應該會招募 75 到 90 名受試者。讓我們更接近 2026 年上半年的第二次數據讀數。我們的市值已超過 1,400 萬美元，流通股數為 1,410 萬股。我們的交易量很健康，3 個月的交易量接近每天 600 萬股。它很尖銳。由於沃利和保羅剛才提到的歐盟消息，上週一我們的交易量約為 240 萬股。

Now, we've been busy by looking at this chart. We've delivered on contracting sites, site selections, presenting presentations, medical posters on MB-106, and also on our sponsored research at MD Anderson. Most importantly, is what we announced Monday, the approval of the EU member countries. Obtaining all of these approvals with just 17 employees supported by a great team of consultants on the timeline which we expected, and we told the public is something of which we're very proud.

現在，我們正忙著看這張圖表。我們完成了簽約場地、場地選擇、演示、MB-106 醫學海報以及我們在 MD Anderson 贊助的研究。最重要的是我們週一宣布的歐盟成員國的批准。我們只用 17 名員工，在一支優秀顧問團隊的支持下，按時獲得了所有這些批准，並向公眾公佈了這一消息，我們對此感到非常自豪。

This sets the stage for announcing outside of the EU and in the US additional country regulatory approvals, along with first by country hospital site initiation visits, which sets them up to be open to recruitment. We'll update you on recruitment on our path to get to the initial 45 subjects. 15 of the control arm and 30 with the two different doses of Annamycin. Now this safety and efficacy readout, in addition to the MB-106 data, should provide the market enough data to support a substantial increase in our market cap. Wally?

這為在歐盟以外和美國宣布獲得其他國家監管部門的批准奠定了基礎，同時也首次對該國醫院進行現場啟動訪問，為招募做好準備。我們將向您通報招募過程中的最新消息，以達到最初的 45 個目標。對照組有 15 人，接受兩種不同劑量 Annamycin 治療的患者中有 30 人。現在，除了 MB-106 數據之外，這個安全性和有效性讀數應該為市場提供足夠的數據來支持我們市值的大幅成長。沃利？

Thanks John. From a big picture perspective, we are all intensely focused on pushing Moleculin's market cap into the range that it truly deserves, and we think the building blocks for that market cap breakout are well placed. Annamycin is a truly disruptive technology in a space where exit valuations are often measured in the billions. The fact is we are positioned to possibly become the first ever non-cardiotoxic anthracycline. And don't forget, anthracyclines are used to treat not just AML but nearly half of all cancers and 60% of all childhood cancers. And Moleculin doesn't just avoid cross resistance with other anthracyclines and chemotherapies like venitoclax, it actually outperforms current anthracyclines in most preclinical tumor models. It's not just that we believe we have a better drug here. It's far more clinically advanced than we think the market is giving us credit for. Our phase 2 efficacy data is better than any drug ever approved for second line AML therapy, and we should have phase 3 data to share publicly by the second half of this year. All of this is supported by a diverse pipeline of follow-on technologies. And it's managed by a truly veteran drug development team with multiple FDA approvals and big pharma exits to our names. The key milestones are coming quickly this year. So, stay tuned for a wild ride at Moleculin. Operator, we're now ready to open up for Q&A.

謝謝約翰。從宏觀角度來看，我們都高度重視將 Moleculin 的市值推向其真正應得的範圍，我們認為實現市值突破的基礎已經到位。在退出估值通常以數十億美元計的領域，Annamycin 是一項真正顛覆性的技術。事實上，我們有可能成為第一個無心臟毒性的蒽環類藥物。別忘了，蒽環類藥物不僅用於治療急性髓性白血病 (AML)，還用於治療近一半的癌症和 60% 的兒童癌症。Moleculin 不僅避免了與其他蒽環類藥物和化療藥物（如 venitoclax）的交叉抗藥性，而且在大多數臨床前腫瘤模型中，它的表現實際上優於目前的蒽環類藥物。我們不僅僅相信我們有更好的藥物。它的臨床先進程度遠遠超出了市場對我們的認可。我們的 2 期療效數據比任何已獲批准用於二線 AML 治療的藥物都要好，並且我們應該在今年下半年之前公佈 3 期數據以供公眾分享。所有這些都得到了多種後續技術的支持。它由一支真正經驗豐富的藥物開發團隊管理，該團隊已獲得多項 FDA 批准，並以我們的名義退出大型製藥公司。今年，關鍵的里程碑正在迅速到來。因此，請繼續關注 Moleculin 的瘋狂之旅。接線員，我們現在可以開始問答了。

Thank you. We'll now be conducting a question-and-answer session. (Operator Instructions)

謝謝。我們現在將進行問答環節。（操作員指示）

Thank you. The first question is from the line of Jonathan Aschoff with Roth Capital.

謝謝。第一個問題來自 Roth Capital 的 Jonathan Aschoff。

Thanks. Good morning and congrats on getting MIRACLE and rolling. I was curious, the statement about the results will be submitted as a substantial modification to the EMA. Does that have any negative implications for the timeline of EU approval versus US?

謝謝。早上好，恭喜您獲得 MIRACLE 並開始行動。我很好奇，有關結果的聲明將作為對 EMA 的實質修改提交。這對歐盟和美國的批准時間表有何負面影響？

Well, we don't think so the issue here is, EMA requested some additional GLP preclinical data that we know we can produce, it's just a matter of timing and budgeting. So, the issue here will be how quickly we can complete that GLP testing before the EU countries are allowed to move on to Part B. That said, Jonathan, the timelines that we've built, we would continue to be recruiting in the US sites and the non-EU sites. Even during that interim period in theory. So, the trial really doesn't have to slow down, and it, and we will, we believe we will get to the requisite number of EU patients to satisfy EU approval requirements. So, the answer is in theory, it shouldn't change the timeline for approval for EMA, but we have to acknowledge that depending on the time it takes to get those GLP studies done. That it could, but that's not our expectation.

嗯，我們不這麼認為，這裡的問題是，EMA 要求提供一些我們知道我們可以提供的額外 GLP 臨床前數據，這只是時間和預算的問題。因此，這裡的問題是，在歐盟國家獲準進入 B 部分之前，我們能多快完成 GLP 測試。話雖如此，喬納森，我們將繼續按照已製定的時間表在美國站點和非歐盟站點招募人員。理論上，即使在那段過渡時期也是如此。因此，試驗確實不必放慢速度，而且我們相信我們將達到滿足歐盟批准要求的必要數量的歐盟患者。因此，答案是理論上它不應該改變 EMA 批准的時間表，但我們必須承認這取決於完成 GLP 研究所需的時間。這是有可能的，但這不是我們的期望。

Okay, how close is Emory, you think to getting an optimum formulation like, in the bag by the end of this year or is it something that could drag out a little?

好的，您認為埃默里大學距離在今年年底前獲得最佳方案還有多遠，還是說這可能會拖延一段時間？

The thing, every time you ask a scientist to give you a timeline for discovering something new, they'll give you a lecture on what it takes to discover something new, right? We're, we think we're beyond the having to discover something new stage and that we, where we are now is actually implementing a strategy for a new formulation that that satisfies the needs for IV delivery. So, we feel like we're now in blocking and tackling and just getting the pre-clinical work done so that we can move this into clinic. And I feel like your sort of estimate there for by the end of the year is a is a decent target. But I do have to acknowledge things can always, you can always get speed bumps when you're developing a new formulation. So, we don't want to overpromise there, but I think, I think you should expect to hear something from us before the end of the year.

問題是，每次你要求科學家給出發現新事物的時間表時，他們都會告訴你發現新事物需要什麼，對嗎？我們認為我們已經超越了必須發現新事物的階段，我們現在實際上正在實施一種滿足靜脈注射需求的新配方策略。因此，我們感覺我們現在正處於阻止和解決問題階段，只需完成臨床前工作，以便我們可以將其轉移到臨床。我覺得你今年年底的估計是一個不錯的目標。但我必須承認，在開發新配方時，事情總是會遇到障礙。所以，我們不想做出過多的承諾，但我認為，我認為你應該會在年底之前聽到我們的消息。

Okay, that's very fair. One for Jon, please. Is that $3.5 million sort of a fair run rate for R&D, for the rest of the year's quarters, or is that, I mean that should go up, shouldn't it?

好的，這非常公平。請給喬恩一個。對於今年剩餘的季度來說，350 萬美元是研發的合理運作率嗎？或者說，這個數字應該會上升，不是嗎？

Yeah, it'll go up especially as we head into 2026 and we bring on the GLP and some manufacturing expenses. Right now, we have enough drugs for part A. We have to start manufacturing drug for Part B.

是的，它會上升，特別是當我們進入 2026 年並引入 GLP 和一些製造費用時。目前，我們有足夠的 A 部分藥物。我們必須開始生產 B 部分的藥物。

Great, thank you very much, guys.

太好了，非常感謝你們。

Thank you. The next question is on the line of Jason McCarthy with Maxim Group.

謝謝。下一個問題來自 Maxim Group 的 Jason McCarthy。

Hey guys, thank you for taking the questions. Good morning, you mentioned the primary is the 35-day CRA, call it one month just for simplicity. Do you need any durability data for potential approval or is 1 month enough? And what are really the expectations for Cytarabine alone, and if CRs are achieved with Cytarabine, how long do they typically last? I'm trying to get a sense of what the bar is going to be here when you get to that unblinded intern data and say like, this looks like this should carry through all the way to the end for an approvable drug.

嘿夥計們，感謝你們回答問題。早安，您提到主要的是 35 天的 CRA，為了簡單起見，稱之為一個月。您是否需要任何耐久性數據來獲得潛在批准，或者 1 個月是否足夠？單獨使用阿糖胞苷的真正預期是什麼？如果使用阿糖胞苷實現了 CR，那麼通常可以持續多久？我試圖了解，當你獲得未盲實習生數據並說這看起來應該持續到可批准藥物​​的最後時，這裡的標準會是什麼。

Well, I'm going to ask Paul to to sort of give you a more thorough answer, Jason, but the good news, just to be really clear, the good news is durability is not a primary endpoint for approval here. It's a secondary objective, so our approval doesn't depend on that, but it's still an interesting topic, and I think it's important to talk about. So Paul, do you want to maybe give a more thorough response to Jason here?

好吧，傑森，我會請保羅給你一個更徹底的答案，但好消息是，要非常清楚，好消息是耐久性不是這裡批准的主要終點。這是次要目標，所以我們的批准並不取決於此，但這仍然是一個有趣的話題，我認為值得討論。那麼保羅，你是否想在這裡給傑森一個更徹底的回應？

That's a good question. As well he said, FDA said that's our primary endpoint and these studies I quoted that had the 17 to 18% CR rate with high dose Cytarabine. These were not small studies. These were studies where the control arm of Cytarabine plus placebo had hundreds of patients. So, we're therefore quite confident that in our trial, the CR rate with Cytarabine is going to be in the teens. It will, as far as durability it will last for a few months, but that's a secondary endpoint. Of course, the ultimate arbitrator is FDA, but at our end of phase 1-2 meeting, they said that's our end point and they understand that we are not powered to show statistical significance for, we're not reasonably powered to show statistical significance to these other ones. There should be a strong trend. This is because that's what the FDA asked for. And when you look at the recent approvals for AML drugs, CR rate was the primary endpoint. The secondaries were overall survival durability. Those were trends. They never reached statistical significance for these drugs, so we think we're in good shape there. And certainly, if we are anywhere near the 50% CR rate, we're in great shape.

這是個好問題。他還說，FDA 表示這是我們的主要終點，我引用的這些研究表明，高劑量阿糖胞苷的 CR 率為 17% 至 18%。這些並不是小型研究。在這些研究中，阿糖胞苷加安慰劑的對照組有數百名患者。因此，我們非常有信心，在我們的試驗中，阿糖胞苷的 CR 率將在十幾歲。就耐用性而言，它將持續幾個月，但這是次要的終點。當然，最終的仲裁者是 FDA，但在我們第 1-2 階段會議結束時，他們說這是我們的終點，他們明白我們沒有能力證明統計意義，我們沒有合理的能力證明這些其他方面的統計意義。應該會有一個強勁的趨勢。這是因為這是 FDA 的要求。當您查看最近批准的 AML 藥物時，CR 率是主要終點。次要因素是整體存活耐久性。這些都是趨勢。這些藥物從未達到統計學意義，因此我們認為我們的情況良好。當然，如果我們的 CR 率接近 50%，那麼我們的狀況就很好了。

There's a nuance here to Jason that I think is important to feed in. And that is the prior studies that Paul mentioned. Two specifically, the Mirros trial and the Classic 1 trial. Both of those studies allowed multiple cycles of Cytarabine before measuring for CR. So that's a difference between their trial designs and ours. In our trial, you only get one cycle, you only get that roughly 35 days, and that's when we measure. So, if the patient can't get a CR off of a single cycle of Cytarabine plus placebo, then that counts as not a CR. So, what partly why Paul said we expected to be in the teens, what he didn't say was our instincts say it's probably going to be lower than that 17.5% because those patients were allowed more than one cycle of Cytarabine. In ours, they won't get more than one cycle. So, logic says that we should expect that number to be lower. Now we're not statistically planning on that, but it's what we expect.

我認為傑森在這裡有一個細微差別，這一點很重要。這就是保羅提到的先前的研究。具體來說，有兩個，Mirros 試用版和 Classic 1 試用版。這兩項研究均允許進行多輪阿糖胞苷治療後再測量 CR。這就是他們的試驗設計和我們的試驗設計之間的區別。在我們的試驗中，您只有一個週期，大約只有 35 天，這就是我們測量的時間。因此，如果患者無法透過單週期阿糖胞苷加安慰劑治療獲得 CR，那麼就不算是 CR。所以，保羅說我們預計在十幾歲的時候，他沒有說的是我們的直覺告訴我們它可能會低於 17.5%，因為這些患者被允許使用一個以上的阿糖胞苷週期。在我們的系統中，它們不會獲得超過一個週期。因此，從邏輯上講，我們應該預期這個數字會更低。目前我們還沒有對此進行統計規劃，但這是我們所期望的。

And I'd imagine that some of your results or could they be impacted by underlying factors like age and mutational genomic alterations of those things that will be considered when you announce the data.

我認為您的一些結果可能會受到年齡和突變基因組改變等潛在因素的影響，這些因素會在您公佈數據時被考慮。

Well, for sure, we will. We'll stratify by age and by genetic mutations, but our primary endpoint isn't dependent upon it. And interestingly, when you look at the phase two data that we that we've talked about, that Paul's talked about, we're pretty agnostic to what genetic mutations are and to what prior therapies were. So, our view is, we're glad for all comers. It's a funny, just an anecdotal story. When Paul and I presented this protocol to a number of practitioners, a common theme from the practitioner was, well, we assume you're going to exclude Venetoclax failures because they're so difficult to treat. And our answer is no, absolutely not. Bring them on. We are not excluding Venetoclax failures. In fact, we're hoping for them because the results are so dismal for those patients. And our phase two data says, we deliver essentially the same CR rate for Venetoclax failures as we do for anybody else. So, we're not sensitive to those differentiations in terms of, obviously, fitness for intensive chemotherapy is largely determined by age. So, there's also the assumption that we are adverse to elderly patients, and that's just not the case. Our median age in the phase two data set was in the 60s. And so, we're happy to have elderly patients and we're happy to have mutational abnormalities and Venetoclax failures.

嗯，我們一定會的。我們將根據年齡和基因突變進行分層，但我們的主要終點並不依賴它。有趣的是，當你查看我們所討論過的第二階段數據，保羅所討論過的數據時，我們對基因突變是什麼以及之前的治療方法是什麼並不清楚。因此，我們的觀點是，我們為所有人的到來感到高興。這是一個有趣的軼事。當保羅和我向一些醫生介紹這個方案時，醫生們的一個共同主題是，我們假設你會排除 Venetoclax 失敗的情況，因為它們很難治療。我們的答案是否定的，絕對不是。帶他們來吧。我們並不排除 Venetoclax 失敗的可能性。事實上，我們對他們抱持希望，因為這些病人的治療結果非常糟糕。我們第二階段的數據表明，我們對 Venetoclax 失敗的 CR 率與對其他失敗的 CR 率基本相同。因此，我們對這些差異並不敏感，顯然，強化化療的適應性很大程度取決於年齡。因此，有人認為我們不利於老年患者，但事實並非如此。我們第二階段資料集中的中位數年齡是 60 多歲。因此，我們很高興有老年患者，我們很高興有突變異常和 Venetoclax 失敗。

Thank you. This will conclude today's question and answer session, and we'll also conclude today's call. Thank you for your participation. You may now disconnect your lines this time. Have a wonderful day.

謝謝。今天的問答環節就此結束，今天的電話會議也到此結束。感謝您的參與。這次您可以斷開線路了。祝您有美好的一天。