Aptose Biosciences Inc (APTO) 2024 Q1 法說會逐字稿

Good afternoon. My name is Josh, and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences conference call for the first quarter ended March 31, 2024. (Operator Instructions) As a reminder, this conference call may be recorded.

午安.我叫喬什，今天我將擔任你們的會議操作員。我謹歡迎大家參加 Aptose Biosciences 於 2024 年 3 月 31 日結束的第一季的電話會議。（操作員說明）謹此提醒，本次電話會議可能會被錄音。

I would like to introduce Ms. Susan Pietropaolo, please go ahead.

我想介紹一下Susan Pietropaolo女士，請介紹。

Thank you, Josh. Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the first quarter ended March 31, 2024. Earlier today, Aptose issued a press release relating to the financial results. The news release, as well as related SEC filings are accessible on Aptose's website.

謝謝你，喬許。下午好，歡迎參加 Aptose Biosciences 電話會議，討論截至 2024 年 3 月 31 日的第一季的財務和營運業績。今天早些時候，Aptose 發布了有關財務業績的新聞稿。該新聞稿以及相關的 SEC 文件可在 Aptose 網站上取得。

Joining me on today's call are Dr. William Rice, Chairman, President and CEO; Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer; and Mr. Fletcher Payne, Senior Vice President, Chief Financial Officer and Chief Business Officer.

與我一起參加今天電話會議的還有董事長、總裁兼執行長 William Rice 博士； Rafael Bejar 博士，資深副總裁兼首席醫療官； Fletcher Payne 先生，資深副總裁、財務長兼商務長。

Before we proceed, I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of US and Canadian securities laws. Forward-looking statements reflect Aptose's current expectations regarding future events, they are not guarantees of performance, and it is possible that actual results and performance could differ materially from these stated expectations.

在我們繼續之前，我想提醒大家，本次電話會議中所做的某些陳述將包括美國和加拿大證券法含義內的前瞻性陳述。前瞻性陳述反映了 Aptose 目前對未來事件的預期，它們不是業績的保證，實際結果和業績可能與這些陳述的預期有重大差異。

They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievement to differ materially from those expressed. To learn more about these risks and uncertainties, please read the risk factors set forth in Aptose's most recent quarterly report on Form 10-Q and SEC and SEDAR filings.

它們涉及已知和未知的風險、不確定性和假設，可能導致實際結果、績效和成就與所表達的結果有重大差異。要了解有關這些風險和不確定性的更多信息，請閱讀 Aptose 最近的 10-Q 表格季度報告以及 SEC 和 SEDAR 文件中列出的風險因素。

All forward-looking statements made during this call speak only as of the date they are made. Aptose undertakes no obligation to revise or update the statements to reflect events or circumstances after the date of this call, except as required by law. We encourage you to refer to today's press release and the 10-Q for additional information and disclosures regarding today's announcements.

本次電話會議期間發表的所有前瞻性聲明僅代表發表之日的情況。除法律要求外，Aptose 不承擔修改或更新聲明以反映本次電話會議之後發生的事件或情況的義務。我們鼓勵您參閱今天的新聞稿和 10-Q，以了解有關今天公告的更多資訊和揭露。

I will now turn the call over to Dr. Rice.

我現在將把電話轉給賴斯醫生。

Thank you, Susan. I want to welcome everyone to our call for the first quarter ended March 31, 2024. Our last call was only about a month and a half ago. So, we've decided to switch up our conference call format today to include a selection of slides that can provide you with a better understanding of our clinical strategy to focus the development of tuspetinib as a triple drug combination or triplet frontline therapy to treat newly diagnosed AML patients.

謝謝你，蘇珊。歡迎大家參加我們關於截至 2024 年 3 月 31 日的第一季的電話會議。我們最後一次通話是在大約一個半月前。因此，我們決定改變今天的電話會議形式，加入精選的幻燈片，讓您更好地了解我們的臨床策略，重點開發 tuspetinib 作為三聯藥物組合或三聯一線療法來治療新的疾病確診的 AML 患者。

Tuspetinib or TUS, as we refer to it, is Aptose's lead clinical asset. TUS is being combined with venetoclax or VEN and a hypomethylating agent for HMA. This forms the TUS+VEN+HMA triplet drug combination that is being developed for frontline therapy to treat newly diagnosed AML patients.

Tuspetinib 或我們所說的 TUS 是 Aptose 的主要臨床資產。TUS 與 Venetoclax 或 VEN 以及 HMA 的低甲基化劑合併使用。這形成了 TUS+VEN+HMA 三重藥物組合，該組合正在開髮用於治療新診斷的 AML 患者的一線治療。

VEN+HMA is currently the standard-of-care therapy for newly diagnosed AML patients and TUS is being bolted on to VEN+HMA standard-of-care to boost the activity and to do so safely. And importantly, we expect to report clinical data with the TUS+VEN+HMA triplet and the newly diagnosed AML patients during the second half of this year.

VEN+HMA 目前是新診斷的 AML 患者的標準護理療法，TUS 正在與 VEN+HMA 標準護理相結合，以增強活性並安全地進行。重要的是，我們預計在今年下半年報告 TUS+VEN+HMA 三聯體和新診斷的 AML 患者的臨床數據。

We all know AML is a highly aggressive cancer of the blood and bone marrow and that unmet need still exists for the relapsed or refractory patient population and for the newly diagnosed population. I'll remind you when we began clinical trials with TUS as a single agent and with the TUS+VEN doublet in the relapsed or refractory AML population, as is the case with many other new cancer drugs. Yet we've always planned to move tuspetinib into frontline therapy for newly diagnosed AML patients.

我們都知道 AML 是一種高度侵襲性的血液和骨髓癌症，對於復發或難治性患者族群以及新診斷族群來說，仍然存在未滿足的需求。我會提醒您，當我們開始在復發或難治性 AML 族群中進行 TUS 作為單藥和 TUS+VEN 雙藥臨床試驗時，就像許多其他新癌症藥物的情況一樣。然而，我們一直計劃將 tuspetinib 納入新診斷的 AML 患者的第一線治療。

Our trials with TUS single agent and with TUS+VEN doublet and relapsed or refractory patients are now completed. The single agent and the doublet demonstrated excellent safety profiles and distinguished tuspetinib from other agents.

我們對 TUS 單藥和 TUS+VEN 雙藥以及復發或難治性患者的試驗現已完成。單藥和雙藥表現出優異的安全性，並將 tuspetinib 與其他藥物區分開來。

Just as important, we observed responses in patients with wild type FLT3 patients with mutated FLT3 patients with mutated TP53 and RAS genes, patients who failed prior therapies with venetoclax/hypomethylating agents, FLT3 inhibitors, and chemotherapy and those who had failed prior stem cell transplants illustrating tuspetinib achieved responses across a remarkable diversity of AML populations.

同樣重要的是，我們觀察了野生型FLT3 患者、突變型FLT3 患者（TP53 和RAS 基因突變）、先前使用維奈托克/低甲基化藥物、FLT3 抑制劑和化療失敗的患者以及先前幹細胞移植失敗的患者的反應。

During Q1 of this year, we presented our clinical findings to the FDA as part of a protocol amendment to allow for evaluation of the TUS+VEN+HMA triple drug combination for the frontline therapy of newly diagnosed AML patients. That protocol for the triplet and frontline therapy is now open and our clinical team is engaging clinical sites and preparing to initiate dosing of patients on the study.

今年第一季度，我們向 FDA 提交了我們的臨床研究結果，作為方案修訂的一部分，以便評估 TUS+VEN+HMA 三重藥物組合用於新診斷的 AML 患者的一線治療。三聯療法和一線療法的方案現已開放，我們的臨床團隊正在參與臨床站點並準備開始對研究中的患者進行給藥。

I want to explain why we've accelerated our strategy to focus on the frontline triplet in newly diagnosed AML patients. As we began to share safety and efficacy data from the TUS and TUS+VEN trials in relapsed or refractory AML patients with our KOL's in pharma, it became clear that the greatest unmet medical need and greatest opportunity in AML is the development of a superior frontline therapy for the treatment of newly diagnosed AML patients.

我想解釋為什麼我們加快了策略，重點關注新診斷的 AML 患者的前線三聯體。當我們開始與製藥界的KOL 分享復發或難治性AML 患者的TUS 和TUS+VEN 試驗的安全性和有效性數據時，很明顯，AML 中最大的未滿足醫療需求和最大的機會是開發卓越的一線藥物用於治療新診斷的 AML 患者。

It also became clear that the unique safety and broad efficacy properties of tuspetinib fit the desired profile of a third agent to add to the VEN+HMA standard of care backbone and assemble a superior triplet for the frontline therapy.

還清楚的是，tuspetinib 獨特的安全性和廣泛的功效特性符合第三種藥物的期望特徵，可以添加到 VEN+HMA 護理標準骨幹中，並為一線治療組合出卓越的三聯體。

Before we go further, let's first recognize that progress has been made with the introduction of venetoclax to the VEN+HMA doublet and this was the major advancement in the treatment of AML. However, the complete remission response rates are still too low and survival is still too short and frontline therapy. And we all want to see a more effective frontline therapy.

在進一步討論之前，我們首先要認識到，將 Venetoclax 引入 VEN+HMA 雙藥中已經取得了進展，這是 AML 治療的重大進展。然而，完全緩解反應率仍然太低，存活期仍然太短，無法作為第一線治療。我們都希望看到更有效的一線療法。

But there was another important factor, leading our KOLs, pharma, and our internal team to focus on frontline therapy. While venetoclax treatment has resulted in more responses in frontline therapy, there is a double-edged sword with venetoclax.

但還有另一個重要因素，促使我們的 KOL、製藥公司和內部團隊專注於第一線治療。雖然維奈托克治療在一線治療中產生了更多反應，但維奈托克是一把雙面刃。

It turns out that relapsed or refractory patients who have failed prior venetoclax treatment, respond poorly to salvage therapies and even if they achieve a response, the survival timeline is grim on the order of a few months. This tells us we need a new frontline strategy that may be able to help avoid rapid failure of venetoclax-based therapies.

事實證明，先前維奈托克治療失敗的複發或難治性患者對挽救療法的反應很差，即使他們達到了反應，生存時間也很嚴峻，大約只有幾個月。這告訴我們，我們需要一種新的第一線策略，或許能夠幫助避免基於維奈托克的療法迅速失敗。

So, what we need is an exceptional third agent that can boost response rates of VEN+HMA, prolong the duration of responses and survival, improve quality of life, treat a broad spectrum of AML genetic subpopulations, and minimize the likelihood of patients becoming resistant to venetoclax.

因此，我們需要的是一種特殊的第三種藥物，它可以提高VEN+HMA 的反應率，延長反應持續時間和生存期，提高生活質量，治療廣泛的AML 遺傳亞群，並最大限度地減少患者產生抗藥性的可能性維奈托克。

This is a tall order and other potential third agents in development may only address specific genetic subpopulations, while other agents bring their own complicating toxicities to the triplet.

這是一項艱鉅的任務，正在開發的其​​他潛在的第三種藥物可能只針對特定的遺傳亞群，而其他藥物本身會對三聯體帶來複雜的毒性。

This has opened the door for tuspetinib to address the greatest single opportunity in AML, which is the development of a superior frontline therapy to treat newly diagnosed AML.

這為 tuspetinib 解決 AML 中最大的單一機會打開了大門，即開發一種卓越的一線療法來治療新診斷的 AML。

Tuspetinib is a natural third agent for addition to venetoclax and HMA's. Tuspetinib has an excellent safety profile as a single agent and in combination with venetoclax and HMA and with other drugs. Tuspetinib enhances antileukemic activity when combined with venetoclax and HMA's.

Tuspetinib 是 Venetoclax 和 HMA 之外的天然第三種藥物。Tuspetinib 作為單一藥物以及與 Venetoclax 和 HMA 以及其他藥物聯合使用時具有出色的安全性。Tuspetinib 與 Venetoclax 和 HMA 合併使用可增強抗白血病活性。

Tuspetinib has a very broad scope of activity across genetic subgroups of AML, even those who have high-risk mutations in the TP53 and RAS genes. And tuspetinib targets known venetoclax resistance mechanisms and may help minimize the rapid onset of drug resistance.

Tuspetinib 在 AML 遺傳亞群中具有非常廣泛的活性，甚至對 TP53 和 RAS 基因具有高風險突變的亞群也是如此。托培替尼針對已知的維奈托克抗藥性機制，可能有助於最大限度地減少抗藥性的快速發生。

Because of this unique safety, activity and mechanistic profile of tuspetinib, we're developing the TUS+VEN+HMA triplet to become a new standard of care therapy to address the safety, scope, and survival needs of newly diagnosed AML patients.

由於 tuspetinib 獨特的安全性、活性和機制特徵，我們正在開發 TUS+VEN+HMA 三聯體，以成為新的護理治療標準，以滿足新診斷的 AML 患者的安全性、範圍和生存需求。

I now want to present just one more slide because it's important to understand how tuspetinib works and how TUS+VEN show mechanistic complementarity and may minimize drug resistance. And I'll illustrate these mechanistic interactions, the cartoon on the right side of the slide.

我現在只想再展示一張投影片，因為了解 tuspetinib 的工作原理以及 TUS+VEN 如何顯示機制互補性並可能最大限度地減少抗藥性非常重要。我將用幻燈片右側的卡通圖來說明這些機械相互作用。

As you can see, AML cells upregulate key oxygenic signal transduction pathways to drive excessive proliferation and cell division. At the same time, AML sales avoid cell death by modifying the exploration of anti-apoptotic proteins such as MCL1 and BCL2. Often in an AML, the BCL2 protein is up regulated.

如您所見，AML 細胞上調關鍵的氧訊號傳導路徑，以驅動過度增殖和細胞分裂。同時，AML銷售透過修改MCL1和BCL2等抗凋亡蛋白的探索來避免細胞死亡。通常在 AML 中，BCL2 蛋白表現上調。

Venetoclax is administered to patients to target the BCL2 and enable the AML cells to die more readily. However, venetoclax alone has minimal efficacy in AML. That's why venetoclax is combined with the hypomethylating agents to achieve clinical remissions.

Venetoclax 給予患者以靶向 BCL2 並使 AML 細胞更容易死亡。然而，單獨使用維奈托克對 AML 療效甚微。這就是為什麼維奈托克與低甲基化藥物聯合使用以實現臨床緩解。

Unfortunately, over time, the cells can modify a number of key pathways to generate resistance to venetoclax. Multiple mutations can occur simultaneously in the FLT3 and KIT receptor kinases and the JAK kinases of the JAK/STAT pathway and in the RAS MAP kinase pathway, all leading to upregulation of the MCL1 anti-apoptotic protein.

不幸的是，隨著時間的推移，細胞可以改變許多關鍵途徑，從而產生對維奈托克的抗藥性。JAK/STAT 路徑的 FLT3 和 KIT 受體激酶以及 JAK 激酶以及 RAS MAP 激酶路徑中可以同時發生多種突變，所有這些突變都會導致 MCL1 抗凋亡蛋白的上調。

Collectively these alterations allow AML sales to drive cell division and avoid to cell death even in the presence of venetoclax. Now, let's look at the effects of tuspetinib. Tuspetinib directly inhibits the FLT3 kinase, the mutant form of KIT, the SYK and JAK Kinases and the JAK/STAT pathway, and the RSK2 kinases downstream in the RAS/MAP kinase pathway and indirectly reduces MCL-1 expression.

總的來說，這些改變使得 AML 銷售能夠驅動細胞分裂，並避免細胞死亡，即使在存在維奈托克的情況下也是如此。現在，我們來看看tuspetinib的作用。Tuspetinib 直接抑制 FLT3 激酶、KIT 突變形式、SYK 和 JAK 激酶以及 JAK/STAT 路徑以及 RAS/MAP 激酶路徑下游的 RSK2 激酶，並間接降低 MCL-1 表現。

It's this mechanistic complementary that can make tuspetinib and venetoclax such a powerful combination tool against AML. And Dr. Bejar will describe how we plan to use these agents together more effectively to treat payment.

正是這種機制上的互補使得 tuspetinib 和 Venetoclax 成為對抗 AML 的強大組合工具。Bejar 博士將描述我們計劃如何更有效地結合使用這些藥物來處理付款。

With that, I'll now turn it over to Dr. Bejar, Aptoses, Chief Medical Officer and Resident, KOL, for his insights into the AML patient journey and to take you through our clinical plan that is already well in place. Raf?

現在，我將把它交給首席醫療官兼住院醫師、KOL Bejar 博士，他對 AML 患者旅程的見解，並帶您了解我們已經制定好的臨床計劃。拉夫？

Thank Will. So to follow on what you just said, I'd like to describe a little bit about the context in which we're developing tuspetinib, namely the AML landscape today and how it is the patients are treated. So a newly diagnosed AML patient would likely receive some form of therapy.

謝謝威爾。因此，按照您剛才所說的，我想描述一下我們開發 tuspetinib 的背景，即當今的 AML 情況以及患者的治療方式。因此，新診斷的 AML 患者可能會接受某種形式的治療。

On rare occasions patients who have too many comorbidities may elect for palliative care, but the majority of patients receive some sort of therapy in first line.

在極少數情況下，患有太多合併症的患者可能會選擇安寧療護，但大多數患者會在第一線接受某種治療。

The younger individuals, generally patients younger than age 70 will receive a form of intensive chemotherapy if they are fit enough to tolerate this kind of therapy. So it has the potential for curing a subset of patients and has a very high complete remission rate.

年輕的個體，通常是 70 歲以下的患者，如果他們的身體狀況足以耐受這種治療，他們將接受某種形式的強化化療。因此它有可能治愈一部分患者，並且具有非常高的完全緩解率。

However, the average age of patients today now is about 68, meaning that the majority of patients it may not be great candidates for high-intensity chemotherapy, instead, what we've seen lower intensity therapy in the frontline consisting of venetoclax plus hypomethylating agent, which has become the standard of care in the past few years.

然而，現在患者的平均年齡約為 68 歲，這意味著大多數患者可能不適合高強度化療，相反，我們在一線看到由維奈托克加低甲基化劑組成的較低強度治療，這已成為過去幾年的護理標準。

This as the complete remission rate of about 37% and a composite complete remission rate that includes incomplete count recovery of about 66%, and we two-third of patients achieving some form of complete remission, and median overall survival to the therapy in the frontline setting is about 15 months.

完全緩解率約為 37%，綜合完全緩解率（包括約 66% 的不完全計數恢復），三分之二的患者實現了某種形式的完全緩解，一線治療的中位總生存期設定時間約為15個月。

Now what can happen to individuals after they achieve complete remission? Ideally, a candidate who might be able to receive an allogeneic stem cell transplant would do so is that it's potentially curative therapy, and they may receive maintenance therapy after that kind of treatment.

現在，個體獲得完全緩解後會發生什麼事？理想情況下，能夠接受異體幹細胞移植的候選人會這樣做，因為它是潛在的治癒性治療，並且他們可能在這種治療後接受維持治療。

Alternatively, a patient who achieved complete remission is not a candidate for stem cell transplant may receive maintenance therapy alone or no therapy as they are hopefully in a deep remission.

或者，達到完全緩解的患者不適合幹細胞移植，可以單獨接受維持治療或不接受任何治療，因為他們有望達到深度緩解。

However, patients may be primarily refractory to initial treatment, meaning they never achieved a complete remission and are immediately considered therapeutically, refractory or they may achieve a remission and even undergo transplant in some cases and yet still relapse and have what we can consider therapeutic failure. And outcomes in patients who have refractory or relapsed disease is quite dismal. And therefore, it is really important to try to prevent this outcome.

然而，患者可能對初始治療主要是難治性的，這意味著他們從未達到完全緩解，並立即被認為是治療難治性的，或者他們可能達到緩解，甚至在某些情況下接受移植，但仍然復發，並出現我們可以認為治療失敗的情況。患有難治性或復發性疾病的患者的結果非常令人沮喪。因此，努力防止這種結果非常重要。

In other words, try to improve the likelihood that patients remain in remission for a longer with frontline therapy because the best way to treat relapsed, refractory disease is to make sure that it doesn't happen in the first place.

換句話說，嘗試提高患者透過第一線治療保持更長時間緩解狀態的可能性，因為治療復發、難治性疾病的最佳方法是確保它從一開始就不會發生。

So, why do I say that we still can improve upon HMA+VEN as it has become the new standard for the treatment of older individuals unfit for intensive induction chemotherapy. From the VIALE -- trial that led to the approval of HMA plus venetoclax as the frontline standard for older unfit individuals, we can break down the benefit in different subpopulations.

那麼，為什麼我說我們仍然可以改進 HMA+VEN，因為它已經成為治療不適合強化誘導化療的老年個體的新標準。VIALE 試驗導致 HMA 加維奈托克被批准作為老年不健康個體的一線標準，我們可以細分不同亞群的益處。

Those individuals that have a more favorable genetic profile, namely they did not have mutations in TP53, FLT3, or NRAS or KRAS, they had the greatest benefit from this kind of therapy. In fact, their median overall survival was over two years.

那些具有更有利的遺傳特徵的個體，即他們沒有 TP53、FLT3、NRAS 或 KRAS 突變，他們從這種治療中獲益最大。事實上，他們的中位總存活期超過兩年。

However, there were some patients that do have some high-risk mutations, they might be in the intermediate benefit category, namely those individuals with FLT3 ITD mutations or mutations downstream of FLT3 ITD in KRAS or NRAS and their benefit wasn't even half as good. Their median overall survival was only about 12 months.

然而，也有一些患者確實有一些高風險突變，他們可能屬於中等獲益類別，即那些在KRAS 或NRAS 中具有FLT3 ITD 突變或FLT3 ITD 下游突變的個體，他們的獲益甚至不及FLT3 ITD 突變的一半。他們的中位總存活期僅為 12 個月左右。

And then there was about a quarter of patients who have a TP53 mutation. Those patients have the worst outcomes. The median overall survival was less than six months and apparently, had a little benefit with the addition of venetoclax over an HMA alone.

還有大約四分之一的患者有 TP53 突變。這些患者的結果最差。中位總存活期不到六個月，顯然，添加 Venetoclax 比單獨使用 HMA 有一點好處。

So, there is substantial room for improvement, particularly in these patients that have these proliferative signaling mutations in FLT3 and NRAS and KRAS to improve upon the outcomes that they see with an HMA or venetoclax. And that is where I think we have a prime opportunity for tuspetinib.

因此，還有很大的改進空間，特別是對於那些在 FLT3 和 NRAS 和 KRAS 中存在增殖訊號突變的患者，以改善他們使用 HMA 或 Venetoclax 看到的結果。我認為這就是我們對 tuspetinib 的絕佳機會。

So, let's talk about that. What are the opportunities for the drug. We know that AML is a disease that has about 21,000 cases annually in the US and with more than half of the patients succumbing to the disorder each year.

那麼，我們來談談這個吧。該藥物的機會是什麼？我們知道，AML 是一種在美國每年約有 21,000 例病例的疾病，每年有超過一半的患者死於這種疾病。

As I mentioned, the median age is 68, meaning that the majority of patients are close to that age where induction chemotherapy is not a common option and survival is still relatively poor, especially for those older individuals where five-year overall survival rates are estimated to be less than 10%.

正如我所提到的，中位年齡為 68 歲，這意味著大多數患者都接近誘導化療不常見的年齡，存活率仍然相對較差，特別是對於那些估計五年總存活率的老年患者低於10%。

Now, frontline therapies have made improvements in the last few years, as Dr. Rice mentioned, I mentioned that the combination of VEN+HMA have about a two-thirds overall response rate for CR and CRI and a 15 month median overall survival, but there are a subset of patients that have inferior outcomes.

現在，一線療法在過去幾年中取得了進步，正如Rice 博士提到的，我提到VEN+HMA 組合的C​​R 和CRI 總體緩解率約為三分之二，中位總體生存期為15 個月，但是有一部分患者的治療效果較差。

We have seen several studies that are combining three agents, venetoclax, HMA, and a novel agent to try to improve outcomes in those frontline patients and we have seen successes there. In particular, trials with kinase inhibitors have shown composite complete remission rates of 80% to 90% in the frontline setting, which is very promising.

我們已經看到了幾項研究，將三種藥物（venetoclax、HMA）和一種新型藥物結合起來，試圖改善第一線患者的治療結果，並且我們已經看到了成功。特別是，激酶抑制劑的試驗顯示，一線治療的複合完全緩解率為 80% 至 90%，這是非常有希望的。

Unfortunately, they do have their own liabilities. In part, they tend to be more toxic when combined in that triplet agent, requiring dose reductions not just of the third novel agent, but of the standard of care backbone of a hypomethylating agent and venetoclax, meaning that the combined therapy is fall short of the standard-of-care for you to give a placebo instead of the third agent.

不幸的是，他們確實有自己的責任。在某種程度上，當它們與三聯藥物組合時往往毒性更大，不僅需要減少第三種新藥物的劑量，還需要減少低甲基化藥物和維奈托克的護理標準，這意味著聯合療法無法達到預期的效果。

And of course, many of these trials have used targeted agents, meaning that they are not applicable to the broader range of AML patients only a subset defined by either genetic or other bio-markers. So, there is an urgent need for a safe and more effective first-line triplet to improve outcomes for AML patients of all genetic subtypes.

當然，其中許多試驗都使用了標靶藥物，這意味著它們不適用於更廣泛的 AML 患者，僅適用於遺傳或其他生物標記定義的子集。因此，迫切需要一種安全且更有效的一線三聯療法來改善所有基因亞型的 AML 患者的預後。

So, how does that fit into the model we drive before. Tuspetinib as an ideal third agent with a very favorable safety profile could be combined both with intensive chemotherapy in the frontline setting as other kinase inhibitors have done and have been approved, or it could be combined as a third agent with venetoclax in HMA in the low-intensity treatment option.

那麼，這如何適應我們之前駕駛的模型呢？Tuspetinib 作為一種理想的第三種藥物，具有非常良好的安全性，可以與一線的強化化療相結合，就像其他激酶抑製劑已經完成並已被批准的那樣，或者它可以作為第三種藥物與Venetoclax 結合用於HMA 中的低- 強度治療選項。

This, I think, provides a broad frontline opportunity for tuspetinib and we have chosen as our first steps in the frontline setting to focus on those low-intensity therapy patients where there are no other drugs currently approved as an applicable triplet for this patient population.

我認為，這為 tuspetinib 提供了廣泛的一線機會，我們選擇將重點放在那些目前沒有其他藥物批准作為適用於該患者群體的三聯藥物的低強度治療患者作為一線設置的第一步。

Doing so allows us to potentially increase the complete remission rates and survival of patients with FLT3 mutations in such a way that doesn't require a reduction of the standard of care. This will permit, for example, a randomized clinical study placebo-controlled that would give standard of care to both arms without having to dose reduce them in the treatment arm.

這樣做使我們能夠以不需要降低護理標準的方式提高 FLT3 突變患者的完全緩解率和存活率。例如，這將允許進行安慰劑對照的隨機臨床研究，該研究將為雙臂提供標準護理，而無需減少治療臂的劑量。

As far as we are aware, this is the only agent being developed in combination with VEN+HMA that includes FLT3 wild type patients or generally patients without a mutational biomarker, which represents the majority of AML patients, of course. And it's the only agent that broadly includes patients with TP53, NRAS, and KRAS mutations in this frontline triplet paradigm.

據我們所知，這是唯一與 VEN+HMA 共同開發的藥物，其中包括 FLT3 野生型患者或通常沒有突變生物標記的患者，當然，這代表了大多數 AML 患者。在這一線三聯體範例中，它是唯一廣泛涵蓋 TP53、NRAS 和 KRAS 突變患者的藥物。

We hope that based on the safety profile to date that the tuspetinib venetoclax HMA combination will be a safer therapy for unfit patients with other triplets that might bring additional toxicities to the table.

我們希望，根據迄今為止的安全性，tuspetinib 與 Venetoclax HMA 組合對於患有其他三聯體的不健康患者來說將是一種更安全的治療方法，這些三聯體可能會帶來額外的毒性。

So, having expressed the landscape of AML and the rationale for a third agent, I want to talk about why tuspetinib is an ideal for agent. As we mentioned, drugs like gilteritinib have been combined with venetoclax and HMA and they've boosted the complete remission rate substantially in the flip mutant population.

因此，在表達了 AML 的概況和第三種藥物的基本原理後，我想談談為什麼 tuspetinib 是一種理想的藥物。正如我們所提到的，像 gilteritinib 這樣的藥物已與 Venetoclax 和 HMA 聯合使用，它們大大提高了翻轉突變人群的完全緩解率。

So, the proof of principle is there that this class of drug can make important advances. But we have seen the limitations that I mentioned that required the dose reductions, now tuspetinib. I think, has an ideal profile as a third agent that might make it superior to these other agents in that frontline setting, and we've learned this from the extensive clinical data we've generated to date with the drug.

因此，原理證明此類藥物可以取得重要進展。但我們已經看到了我提到的限制，需要減少劑量，現在是特培替尼。我認為，作為第三種藥物，它具有理想的特徵，可能使其在一線環境中優於其他藥物，並且我們從迄今為止使用該藥物產生的廣泛臨床數據中了解到了這一點。

We've done extensive testing, both with tuspetinib as a monotherapy and with tuspetinib in combination with venetoclax that tells us that tuspetinib does not have several of the side effects that could impair its further clinical development, including no QTc prolongation related to drug, differentiation syndrome, evidence of muscle damage.

我們已經對 tuspetinib 作為單一療法以及 tuspetinib 與 Venetoclax 聯合進行了廣泛的測試，結果告訴我們 tuspetinib 沒有可能損害其進一步臨床開發的副作用，包括沒有與藥物相關的 QTc 延長、分化綜合症，肌肉損傷的證據。

Or even prolonged myelosuppression in patients who achieved remission where patients in remission continue to take the drug without interruption and maintain their blood counts.

或甚至在獲得緩解的患者中進行長期骨髓抑制，其中緩解中的患者繼續不間斷地服用藥物並維持其血球數。

By combining it with venetoclax in the relapsed refractory setting in a large number of patients, we now understand that there aren't significant drug interactions that would require dramatic dose, changes of either agent or see developing them at their established doses.

透過將其與維奈托克聯合治療大量復發難治性患者，我們現在了解到，不存在顯著的藥物交互作用，需要大幅劑量、改變任一藥物或在既定劑量下觀察到它們的發展。

And importantly, we have favorable comparisons in direct, of course, with other agents out there. We believe that we can see we have demonstrated we can see responses in patients with a prior FLT3 inhibitors that we don't need to inhibit the pathway as substantially as other agents do, perhaps because of the multi-kinase activity of the drug and that we have seen responses in the large proportion of FLT3 unmutated patients, which really differentiates tuspetinib from other agents like tuspetinib.

重要的是，我們與其他代理商進行了直接的比較。我們相信，我們已經證明，我們可以在先前使用過 FLT3 抑制劑的患者中看到反應，我們不需要像其他藥物那樣大幅抑制該通路，這可能是因為該藥物的多激酶活性，並且我們已經在大部分FLT3 未突變患者中看到了反應，這確實將tuspetinib 與tuspetinib 等其他藥物區分開來。

Importantly, we have that superior safety profile, where we are targeting the VEN resistance mechanisms that may potentially help prevent VEN resistance or potentially, even re-sensitize them based on preclinical studies and by suppressing more oncogenic pathways, may be able to alleviate other potential mechanisms of resistance from arising.

重要的是，我們擁有優越的安全性，我們的目標是VEN 抗藥性機制，這可能有助於預防VEN 抗藥性，甚至可能根據臨床前研究使它們重新敏感，並透過抑制更多致癌途徑，可能能夠減輕其他潛在風險抵抗機制的產生。

Therefore, we believe there is a strong rationale for combining tuspetinib with venetoclax in the frontline setting, particularly where patients are like VEN -- to all agents.

因此，我們相信在一線治療中將 tuspetinib 與 Venetoclax 聯合使用是有充分理由的，特別是對於所有藥物都像 VEN 一樣的患者。

So, what have we done to get there. We've completed the single agent dose exploration where we treated a large number of patients that I'll show you, we've demonstrated the activity of the drug as a single agent in select populations both with and without FLT3 mutations, and we've demonstrated a superior safety profile of the drug in that context.

那麼，我們做了什麼才能實現這一目標。我們已經完成了單藥劑量探索，我們治療了大量患者，我將向您展示，我們已經在有和沒有 FLT3 突變的選定人群中證明了該藥物作為單藥的活性，並且我們'在這方面，我們已經證明了該藥物具有卓越的安全性。

In the doublet study is learned about the safety of tuspetinib plus venetoclax, how it could safely be given without substantial dose modification, and we've characterized the CPK of both agents. This has now put us in a position to submit a triplet protocol to the FDA and where we've also achieved orphan drug designation and fast-track status for patients with FLT3 mutations in this drug.

在雙重研究中，我們了解了 tuspetinib 加 Venetoclax 的安全性、如何在不進行大幅劑量調整的情況下安全地給藥，並且我們還描述了兩種藥物的 CPK 特徵。這使我們現在能夠向 FDA 提交三重方案，並且我們還獲得了孤兒藥指定和針對該藥物中存在 FLT3 突變的患者的快速通道狀態。

So, the triplet pilot study has already been implemented and clinical sites are now being prepared to enroll our first patients later this year and we hope to select the optimal dose of tuspetinib that will allow us to maintain the standard of care dosing of the other agents, which would then enable a randomized placebo-controlled registrational study.

因此，三聯體試驗研究已經實施，臨床中心正在準備在今年稍後招募我們的第一批患者，我們希望選擇 tuspetinib 的最佳劑量，這將使我們能夠維持其他藥物的護理劑量標準，這將使得隨機安慰劑對照註冊研究成為可能。

We will learn about how best to give these drug combinations safely and mitigate myelosuppression and we'll characterize the activity in those difficult to treat or less likely to benefit subgroups of patients that have TP53 mutations, NRAS KRAS mutations, as well as several kinds of FLT3 mutations.

我們將了解如何最好地安全地給予這些藥物組合併減輕骨髓抑制，我們將描述那些難以治療或不太可能受益的具有 TP53 突變、NRAS KRAS 突變以及多種類型的患者亞群的活性。 。

We'll further characterize CPK and establish the safety and the efficacy profile and finally, look at what impact we might be having on overall survival before we take our next steps.

我們將進一步描述 CPK 的特徵並建立安全性和有效性概況，最後在採取下一步措施之前看看我們可能對整體生存產生什麼影響。

I want to spend a little bit of time just sharing how we are actually going to be giving these three drugs together, and how this compares to other agent mixes that are out there.

我想花一點時間來分享我們實際上將如何將這三種藥物一起使用，以及與現有的其他藥物混合物相比如何。

For the pilot study, our first triplet in the frontline setting, we're proposing to treat about 20 to 36 patients total. These are patients that are going to be older, ineligible for induction chemotherapy, either because of age over 75 or because of comorbidities that would prevent that kind of more intensive therapy or shoot for 50% of the patients having a FLT3 mutation, so we have an understanding about activity both in the FLT3 mutant and in the FLT3 wild type group, and we'll look at all those other factors that I just described earlier.

對於試驗研究，我們在前線進行的第一個三聯體研究，我們建議總共治療約 20 至 36 名患者。這些患者年齡較大，不符合誘導化療的條件，要么是因為年齡超過 75 歲，要么是因為合併症會阻止這種更強化的治療，或者會導致 50% 的患者出現 FLT3 突變，所以我們有了解FLT3 突變體和FLT3 野生型組的活性，我們將研究我之前描述的所有其他因素。

The way we're going to give the drugs together is by giving VEN and ASA together as a standard-of-care doublet with the addition of daily tuspetinib, as shown in the top graph here.

我們將藥物一起給予的方式是將 VEN 和 ASA 一起作為標準護理雙藥，並每日添加 tuspetinib，如上圖所示。

You can see that at day 18 will perform a bone marrow biopsy and if patients have achieved remission, we will hold venetoclax starting on day 22, and this is consistent with the venetoclax label, that suggests that you begin for 21 days to 28 days per cycle.

你可以看到，在第18天將進行骨髓活檢，如果患者已經達到緩解，我們將從第22天開始保留venetoclax，這與venetoclax標籤一致，即建議您開始每次21天到28天。

We then will allow patients to recover the counts and monitor how long it takes to do so, making adjustments along the way, if necessary. Of course, if a patient has not achieved a remission, then they would continue to take the venetoclax along with the tuspetinib through day 28, when a second bone marrow biopsy will be performed to see if they achieved a remission.

然後，我們將允許患者恢復計數並監控恢復所需的時間，並在必要時進行調整。當然，如果患者尚未達到緩解，那麼他們將繼續服用 Venetoclax 和 tuspetinib，直到第 28 天，屆時將進行第二次骨髓活檢，看看他們是否達到緩解。

And if they have, then allow additional time for the blood count recovery to occur before they move on to their second cycle. The dosing in the second cycle will be adjusted based on the patient's experience with the first. Patients who have no significant myelosuppression would go on to receive the same type of cycle as a second cycle. Those that do will have adjustments to their drugs made according to the VEN, ASA label.

如果有，則在進入第二個週期之前留出額外的時間讓血球計數恢復。第二個週期的劑量將根據患者在第一個週期的經驗進行調整。沒有明顯骨髓抑制的患者將繼續接受與第二個週期相同類型的週期。這樣做的人將根據 VEN、ASA 標籤對其藥物進行調整。

So, now let's talk about milestones and when we are likely to have data. So, coming up very shortly will be the EHA Meeting in Madrid. There, we will present the summary of our single agent and doublet data, really providing an update to what we presented at ASH earlier along these lines in our oral presentation given by Dr. Naval Daver.

那麼，現在讓我們來談談里程碑以及何時我們可能會獲得數據。因此，很快將在馬德里召開 EHA 會議。在那裡，我們將介紹我們的單藥和雙藥數據的摘要，實際上是對我們早些時候在 ASH 上由 Naval Daver 博士進行的口頭報告中提出的內容進行更新。

Shortly after that meeting, we expect to have our first patient enrollment in our frontline triplet study. This will begin the treatment in this frontline patient population if continued approval. And hopefully, the presentation of several patients' worth of data at the Annual Society for Hematology Meeting here in San Diego at the end of near the end of Q4.

那次會議後不久，我們預計將有第一批患者加入我們的第一線三聯體研究。如果繼續獲得批准，這將開始在這一線患者群體中進行治療。希望第四季末在聖地牙哥舉行的血液學協會年度會議上能夠展示幾位患者的數據。

The trial will continue, of course, and we hope to have a more mature summary at next year EHA Meeting in 2025 as we meet with the FDA and prepare for the regulatory steps with multiple milestones for adding additional data along the way.

當然，該試驗將繼續進行，我們希望在明年的2025 年EHA 會議上獲得更成熟的總結，屆時我們將與FDA 會面，並為監管步驟做好準備，並為監管步驟做好準備，其中包括多個里程碑，以便在此過程中添加更多資料。

So, I'll briefly go into some of the frontline some of that monotherapy data and doublet data that gave us the understanding about how to proceed in the frontline. So to summarize, tuspetinib a single agent has now been given to over 91 patients as a monotherapy and it has had a very clean safety profile with, again, no drug-related myelosuppression in patients who achieved remission QTc prolongation, or CPK elevation that would be evidence of muscle damage, and in fact, in the single agent, no drug-related discontinuations or deaths.

因此，我將簡要介紹一些前線的一些單一療法數據和雙重數據，這些數據使我們了解如何在前線進行。總而言之，托培替尼單藥現已作為單一療法用於超過91 名患者，並且它具有非常乾淨的安全性，在實現緩解QTc 延長或CPK 升高的患者中，沒有出現與藥物相關的骨髓抑制。

Here, you can see the percentage of patients with adverse events related to tuspetinib and the most frequent were relatively mild nausea and fatigue with very few grade three or larger related adverse events.

在這裡，您可以看到發生與 tuspetinib 相關的不良事件的患者百分比，最常見的是相對輕微的噁心和疲勞，很少有三級或以上的相關不良事件。

Similar profile occurs when we combined tuspetinib with venetoclax in the doublet with no new or unexpected safety signals arising and very similar rates of adverse events, higher rates of neutropenia, and other myelosuppressive markers as would be expected with the addition of venetoclax is very much in line with, -- would expect for a venetoclax containing regimens, in fact, lower rates of febrile neutropenia than expected.

當我們將托培替尼與維奈托克合併使用時，會出現類似的情況，沒有出現新的或意外的安全訊號，且不良事件發生率非常相似，中性粒細胞減少症發生率較高，其他骨髓抑制標記物也與添加維奈托克所預期的一樣。

And here is the evidence of that single agent activity. This graph here shows evidence of bone marrow blast reductions in patients treated with tuspetinib as a single agent. You can see that more than half of the patients achieved some degree of bone marrow blast reduction.

這是單一代理活動的證據。此圖顯示了使用 tuspetinib 作為單一藥物治療的患者骨髓原始細胞減少的證據。您可以看到超過一半的患者實現了一定程度的骨髓原始細胞減少。

And you can see that this occurred in a variety of different dose levels are shown by the different colors. The other thing I would point out is that patients that had a prior FLT3 inhibitor are marked with a red triangle. And you can see that patients with prior FLT3 inhibitors were just as likely, if not more likely, to show a bone marrow blast reduction.

並且您可以看到，這種情況發生在各種不同的劑量水平上，並透過不同的顏色顯示出來。我要指出的另一件事是，先前使用 FLT3 抑制劑的患者以紅色三角形標記。您可以看到，先前使用過 FLT3 抑制劑的患者即使不是更有可能，也同樣可能表現出骨髓原始細胞減少。

However, patients with prior venetoclax, shown by the black triangles, are less represented in the far right of the graph, consistent with our knowledge that VEN resistant patients are less likely to respond to practically any other therapy as a monotherapy.

然而，黑色三角形所示的既往接受過維奈托克治療的患者在圖表最右側的代表性較少，這與我們的知識一致，即VEN 抗藥性患者不太可能對幾乎任何其他療法作為單一療法產生反應。

For that reason, we performed the doublet study of patients with relapsed, refractory disease, receiving tuspetinib and venetoclax and again saw blast reductions in more than half of the patients.

因此，我們對接受託培替尼和維奈托克治療的復發難治性疾病患者進行了雙重研究，再次發現超過一半的患者的原始細胞減少。

And in contrast to the figure on the left, we now see many more of those black triangles on the far right of the graph, showing that even VEN pretreated patients can have significant blast reductions when treated with the combination of venetoclax and tuspetinib in the relapsed refractory setting.

與左圖相反，我們現在在圖的最右側看到了更多的黑色三角形，這表明即使是接受過VEN 治療的患者，在接受Venetoclax 和tuspetinib 聯合治療時，復發性乳腺癌患者的原始細胞數量也能顯著減少。

And once more, multiple red triangles in the right indicating that patients with prior FLT3 inhibitor are still more likely to respond than patients who don't likely because of their prior FLT3 mutation status.

右側的多個紅色三角形再次表明，先前使用過 FLT3 抑制劑的患者仍然比那些因先前的 FLT3 突變狀態而沒有反應的患者更有可能做出反應。

So now I'll pass on your thoughts to either the Fletcher Payne, who will talk more about the investment thesis and some of the near-term milestones for the drug. Fletcher?

因此，現在我將把您的想法轉達給 Fletcher Payne，他將更多地談論投資論文和該藥物的一些近期里程碑。弗萊徹？

Thanks Raf. Good afternoon all. There are three key points to the TUS investment thesis. First, there's a very high unmet medical need in frontline AML has been discussed before to increase survival across all genetic subtypes. Two the KOL support TUS as the ideal third agent for triplet study in the frontline patients.

謝謝拉夫。大家下午好。啟迪的投資論點有三個要點。首先，之前已經討論過，為了提高所有基因亞型的生存率，在第一線 AML 存在非常高的未滿足醫療需求。兩位 KOL 支持 TUS 作為第一線患者三聯體研究的理想第三種藥物。

Three TUS is emerging as an ideal agent to combine with VEN+HMA. This is due to the safety profile, the broad activity across FLT3 mutated and FLT3 wild type patients as well as activity against difficult-to-treat mutated TP53 and the RAS gene subtypes.

三TUS正成為與VEN+HMA結合的理想劑。這是由於安全性、FLT3 突變型和 FLT3 野生型患者的廣泛活性以及針對難以治療的突變 TP53 和 RAS 基因亞型的活性。

The design of the triple study and the data readout lineup well to generate several near-term value-creating milestones. The first milestone will be at EHA in June 2024, where we will report single agent and double agent activity, which supports our contention to move into the frontline in the triplet study.

三重研究的設計和數據讀出陣容很好地產生了幾個近期價值創造里程碑。第一個里程碑將於 2024 年 6 月在 EHA 舉行，屆時我們將報告單劑和雙劑活動，這支持我們進入三聯體研究前線的主張。

The second milestone will be in the summer of 2024, we will start dosing newly diagnosed patients in our triplet study. The third milestone at ASH 2024, we will report complete responses, MRD negativity, and safety data from the triplet study.

第二個里程碑將是在 2024 年夏天，我們將開始在三聯體研究中對新診斷的患者進行給藥。ASH 2024 的第三個里程碑是，我們將報告三聯體研究的完整緩解、MRD 陰性和安全性數據。

During the first half of 2025, we expect a complete enrollment of the study. The fourth milestone will be at EHA in the summer of 2024, '25 where we will report data readout from the triplet study. So, as you can see, the triplet study provides for a number of value-creating inflection points over the coming year.

我們預計研究將在 2025 年上半年完成註冊。第四個里程碑將於 2024 年夏天在 EHA 舉行，'25 我們將報告三聯體研究的數據讀數。因此，正如您所看到的，三重態研究為來年提供了許多創造價值的轉折點。

Before I cover the first quarter financial highlights, I would like to start by saying that the on our comments in this call, additional information may be found in today's press release and the 10-Q filed with the SEC.

在介紹第一季財務亮點之前，我首先想說的是，關於我們在本次電話會議中的評論，更多資訊可以在今天的新聞稿和向 SEC 提交的 10-Q 中找到。

During the first quarter of 2024, we continued our disciplined financial management of operations. We reduced spending on several fronts and prioritize our investments in our clinical programs. As always, we continue to evaluate ways to reduce operating expenses. The total outstanding share count as of today May 14, is 16,309,393 shares.

2024 年第一季度，我們持續實行嚴格的營運財務管理。我們減少了多個方面的支出，並優先考慮對臨床項目的投資。一如既往，我們繼續評估減少營運費用的方法。截至 5 月 14 日，流通股總數為 16,309,393 股。

Based on current operations, the company expects the cash on hand plus our ATM will provide sufficient resources to fund planned operations, including research and development activities, through August 2024. Last quarter, we informed you that a 2024 deficient deficiency letter from NASDAQ regarding the private placement with Hanmi was and that was announced, which was announced in January.

根據目前的營運情況，公司預計手頭現金加上 ATM 將為 2024 年 8 月之前的計畫營運（包括研發活動）提供充足的資源。上個季度，我們通知您，納斯達克已於 1 月宣布了一份關於 Hanmi 私募的 2024 年缺陷通知書。

Aptose has submitted a plan to NASDAQ to regain compliance. On April 25, of this year, the company received a letter from NASDAQ listing qualifications department, notifying the company. The company had regained compliance with the NASDAQ listing rules 5635(D) and determined that the matter is now closed.

Aptose 已向納斯達克提交了一份計劃以重新獲得合規性。今年4月25日，公司收到納斯達克上市資格部門的函件，通知公司。該公司已重新遵守納斯達克上市規則 5635(D) 的規定，並確定此事現已結束。

Under the company's plan to regain compliance on April 26, 2024. The company announced that it had amended the warrant agreement with Hanmi to prohibit the exercise of Hanmi warrants and success of the NASDAQ 19.99% limitation, unless shareholder approval is for some time.

公司計劃於2024年4月26日恢復合規。該公司宣布已修改與Hanmi的認股權證協議，禁止行使Hanmi認股權證並成功實現納斯達克19.99%的限制，除非股東批准一段時間。

On April 2, 2024, we received the second notification from the NASDAQ, stating that the company was noncompliance with the NASDAQ listing rules because our stockholders' equity as of December 31, 2023 was below the minimum $2.5 million.

2024年4月2日，我們收到納斯達克的第二次通知，表示該公司不符合納斯達克上市規則，因為截至2023年12月31日我們的股東權益低於最低250萬美元。

We intend to submit a compliance plan on or before May 17, 2024 monitor our stockholders' equity and if appropriate, consider further available options to evidence compliance with the stockholder equity requirements.

我們打算在 2024 年 5 月 17 日或之前提交合規計劃，監控我們的股東權益，並在適當的情況下考慮進一步可用的選項來證明遵守股東權益要求。

Now I would like to direct you to review the company's risk factors and discussions regarding the NASDAQ ladder and going concern footnote in our 10-Q and our 10-K filings.

現在我想引導您回顧公司的風險因素以及有關納斯達克階梯的討論以及我們的 10-Q 和 10-K 文件中的持續經營腳註。

Now let's review the first quarter financials. We ended the first quarter of 2024 with approximately $9.3 million in cash, cash equivalents investments approximately -- equal to December 31, 2023. The $11.8 million in net financing proceeds in January 2024 was offset by $11.8 million used to fund our operations for the quarter, including our APTIVATE clinical study for tuspetinib.

現在讓我們回顧一下第一季的財務狀況。截至 2024 年第一季末，我們擁有約 930 萬美元的現金、現金等價物投資，約等於 2023 年 12 月 31 日的金額。2024 年 1 月的 1,180 萬美元淨融資收益被用於為我們本季營運提供資金的 1,180 萬美元所抵消，其中包括我們針對 tuspetinib 的 APTIVATE 臨床研究。

As seen in the income statement, we had no revenues during 2024 or in the first quarter of 2024. During the first quarter of 2024. The net loss was approximately $9.6 million, translating into $0.73 loss per share compared to $13.7 million loss or [$2.22] loss per share from the first quarter of 2023.

從損益表中可以看出，我們在 2024 年或 2024 年第一季沒有收入。2024 年第一季。淨虧損約 960 萬美元，相當於每股虧損 0.73 美元，而 2023 年第一季的虧損為 1,370 萬美元，即每股虧損 [2.22 美元]。

As of May 14, 2024 Aptose, 16,309,393 common shares outstanding. All references to losses per share and shares outstanding had been presented to reflect the 15 for 1 reverse split completed on June 6, 2023.

截至 2024 年 5 月 14 日，Aptose 已發行普通股 16,309,393 股。所有提及每股虧損和已發行股票的資訊均已提交，以反映 2023 年 6 月 6 日完成的 15 換 1 反向分割。

Research and development expenses were approximately $6.4 million for the quarter ended March 31, 2024 compared to $8.8 million for the first quarter of 2023. Program costs for tuspetinib were $3.9 million for the first quarter of 2024 compared to $4.8 million for the first quarter of 2023.

截至 2024 年 3 月 31 日的季度，研發費用約為 640 萬美元，而 2023 年第一季的研發費用為 880 萬美元。2024 年第一季 tuspetinib 的專案成本為 390 萬美元，而 2023 年第一季為 480 萬美元。

Lower program costs for tuspetinib in the current period represent the completion of patient enrollment when our TUS then doublet program and reduce manufacturing costs. Program costs for luxeptinib were $208,000 for the first quarter, and decreased by approximately $1.1 million compared to $1.3 million in the first quarter of 2023, primarily due to lower clinical trial costs and lower manufacturing costs.

當前階段 tuspetinib 專案成本的降低代表著當我們的 TUS 專案加倍並降低製造成本時患者入組的完成。luxeptinib 第一季的專案成本為 208,000 美元，與 2023 年第一季的 130 萬美元相比減少了約 110 萬美元，主要是由於臨床試驗成本和製造成本降低。

G&A expenses were $3.3 million for the first quarter of 2024 and decreased by $2 million compared to $5.3 million for the corresponding period of 2023. The decrease was primarily due to lower professional fees, stock-based compensation in the current period.

2024 年第一季的一般管理費用為 330 萬美元，比 2023 年同期的 530 萬美元減少了 200 萬美元。減少的主要原因是本期專業費用和股票薪酬下降。

Now let me turn back to Dr. Rice.

現在讓我回到賴斯博士身上。

Thank you, Fletcher. Now we'll open the call for questions and please feel free to pose a question to any of us operate. If you can please turn to the quarter.

謝謝你，弗萊徹。現在我們將開始提問，請隨時向我們的任何操作人員提出問題。如果可以的話，請轉到季度。

(Operator Instructions) Joe Pantginis, H.C. Wainwright.

（操作員說明）Joe Pantginis, H.C.溫賴特。

Good afternoon, gentlemen, and thanks for taking the questions and I'll start with two, if you don't mind. So first one on slide number 10, when you presented the on the trial design for the triplet combination, I'm just curious if there, what level of before and after was there. So you met with the FDA in the first quarter, as you said, how much does slide 10, align with what you originally wanted with them?

下午好，先生們，感謝您提出問題，如果您不介意的話，我將從兩個問題開始。因此，第 10 號投影片上的第一個，當您介紹三聯體組合的試驗設計時，我只是好奇是否存在，之前和之後的水平如何。所以你在第一季會見了 FDA，正如你所說，幻燈片 10 與你最初想要的東西有多少一致？

So, Raf perhaps Dr. Bejar perhaps you can answer that one and put it

所以，Raf 也許 Bejar 博士也許你可以回答這個問題並把它說出來

And yes, of course. And so this was developed in conjunction with experts in the field, including our lead, the overarching I will David. We've done several of these frontline triplet studies, And it really reflects both his experience and then is a label. It is not really a consequence of a back-and-forth with the FDA on this.

是的，當然。因此，這是與該領域的專家一起開發的，包括我們的領導，我將大衛。我們已經做了幾項一線三聯體研究，它確實反映了他的經驗，然後是一個標籤。這並不是與 FDA 就此問題反覆討論的結果。

We did submit a protocol amendment to our existing study that includes this protocol more than, I think 45 to 50 days ago now. But this is really a function of our discussions with our experts, not a consequence of discussions with the FDA.

我們確實提交了對現有研究的方案修正案，其中包括該方案，我想是在 45 到 50 天前。但這其實是我們與專家討論的結果，而不是與 FDA 討論的結果。

Raff, that makes sense. Thanks. And then on, I guess as we look to the triplet study now, everyone's going to be highly looking forward to the year end data. So I guess internally, what do you view as the benchmark for success to be able to move beyond the pilot?

拉夫，這是有道理的。謝謝。然後，我想當我們現在關註三重態研究時，每個人都會非常期待年底的數據。所以我想在內部，您認為能夠超越試點的成功基準是什麼？

So, I can take that too Will. There's a couple of opportunities, I think to show benefit here. The expectations are based on prior data that the front-line triplet with a kinase inhibitor like tuspetinib can substantially increase the response rate. Of course, I think that really the metric that really matters is overall survival and that is not data that we expect to have in the short term.

所以，我也可以接受威爾。我認為有幾個機會可以在這裡展示好處。這些預期是基於先前的數據，即使用 tuspetinib 等激酶抑制劑的一線三聯療法可以顯著提高緩解率。當然，我認為真正重要的指標是整體存活率，這不是我們期望在短期內獲得的數據。

But the expectation with the VIALE-A study is that you see about a two thirds of the patients responding. I think if we would see something closer to 75%, I think we'd be comfortable that we are at least meaning that if not exceeding it.

但 VIALE-A 研究的預期是您會看到大約三分之二的患者有反應。我認為，如果我們看到接近 75% 的數字，我想我們會感到放心，因為如果不超過的話，我們至少意味著這個數字。

And given the number of patients we expect at ASH, I wouldn't expect to see a robust value there. But by the time, the study is completely treated enough patients. I think we'll have a very good understanding based on the response metrics about how what we're doing.

考慮到我們預計 ASH 的患者數量，我預計不會在那裡看到強勁的價值。但到那時，該研究已經完全治療了足夠多的患者。我認為，根據回應指標，我們會對我們正在做的事情有一個很好的了解。

Joe, I'll add a little bit to that because it also relates back to the trial design. What we hope to see and we expect to see by year end is the complete remissions in these patients. We expect to see the robust safety, which we've continued to see all the way through even in the doublet of tuspetinib with venetoclax.

喬，我會補充一點，因為它也與試驗設計有關。我們希望看到並預計到年底看到的是這些患者的完全緩解。我們期望看到強大的安全性，即使在 tuspetinib 與 Venetoclax 的雙藥中，我們也一直看到這種安全性。

And we hope in that, that allows us to maintain the standard of care dosing that Dr. Bejar mentioned, because it's really important to be able to maintain the expected levels of venetoclax as well as the hypomethylating agent according to the label of the drug, FDA wants to see that. We want to see that. And that's been a real problem with many of the other drugs out there.

我們希望，這使我們能夠維持 Bejar 博士提到的護理劑量標準，因為能夠根據藥物標籤維持 Venetoclax 以及低甲基化藥物的預期水平非常重要， FDA 希望看到這一點。我們希望看到這一點。這對於許多其他藥物來說是一個真正的問題。

Perhaps Dr. Bejar wants to add to that.

也許貝賈爾博士想補充這一點。

That's exactly right, will.

完全正確，威爾。

Okay.

好的。

Thanks, guys. Appreciate it.

謝謝，夥計們。欣賞它。

Thank you, Joe.

謝謝你，喬。

Thank you. (Operator Instructions) I would now like to turn the call back over to Dr. Rice, for closing remarks.

謝謝。（操作員指示）我現在想將電話轉回給賴斯博士，請他發表結束語。

All right. Well, thank you everyone for joining us this afternoon. We're genuinely excited to take tuspetinib into the frontline trip of therapy for newly diagnosed AML patients.

好的。好的，謝謝大家今天下午加入我們。我們非常高興能夠將 tuspetinib 納入新診斷的 AML 患者的第一線治療中。

And we hope that we relate how Tuspetinib is distinguished from other AML compounds in development, not only because of its safety profile, but because it has shown activity across a broad set of mutations even in wild type AML potentially addressing the largest market in AML, not just a subset.

我們希望我們能夠了解Tuspetinib 與其他正在開發的AML 化合物的區別，不僅因為它的安全性，而且因為它在廣泛的突變中表現出活性，甚至在野生型AML 中也顯示出活性，可能會解決最大的AML 市場，不只是一個子集。

As always, we thank our patients, investigators, and employees for their important role in this effort. Our clinical team has been keen in developing our poly triplet study prepared to getting it prepared. I want to recognize them for their execution.

一如既往，我們感謝患者、研究人員和員工在這項工作中發揮的重要作用。我們的臨床團隊一直熱衷於開發我們的多三聯體研究，並做好準備。我想表彰他們的執行力。

We appreciate our shareholders and analysts who continue to support us and we look forward to keeping you updated on our progress to date and we really do appreciate the questions that came to us today.

我們感謝繼續支持我們的股東和分析師，我們期待向您通報我們迄今為止的進展情況，我們非常感謝今天向我們提出的問題。

I want to thank you and have a good evening.

我想感謝你並祝你晚上愉快。

Thank you. Ladies and gentlemen, that concludes today's conference. You may all disconnect and have a wonderful day.

謝謝。女士們、先生們，今天的會議到此結束。你們可能會斷開連接並度過美好的一天。