Aptose Biosciences Inc (APTO) 2023 Q3 法說會逐字稿

Good afternoon. My name is Hope and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences conference call for the third quarter ended September 30, 2023. (Operator Instructions) As a reminder, this conference call may be recorded. I would now like to introduce Ms. Susan Pietropaolo. Please go ahead.

午安.我叫霍普，今天我將擔任你們的會議操作員。歡迎大家參加截至 2023 年 9 月 30 日的第三季 Aptose Biosciences 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。現在我想介紹一下蘇珊‧彼得羅保羅女士。請繼續。

Thank you, Hope. Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the third quarter ended September 30, 2023. Earlier today, Aptose issued a press release relating to these financial results. The news release as well as related SEC filings are accessible on Aptose's website.

謝謝你，希望。下午好，歡迎參加 Aptose Biosciences 電話會議，討論截至 2023 年 9 月 30 日的第三季度的財務和營運業績。今天早些時候，Aptose 發布了與這些財務業績相關的新聞稿。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 and Chief Financial 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；以及資深副總裁兼財務長 Fletcher Payne 先生。

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. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed.

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。它們不是性能的保證，實際結果和性能可能與這些陳述的預期有重大差異。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。

To learn more about these risks and uncertainties, please read the risk factors set forth in Aptose's most recent annual report on Form 10-K, and SEC, and SEDAR filings. 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 these statements to reflect events or circumstances after the date of this call except as required by law. We encourage you refer today's press release and the 10-Q for additional information and disclosures regarding today's announcements. I will now turn the call over to Dr. Rice.

要了解有關這些風險和不確定性的更多信息，請閱讀 Aptose 最新 10-K 表格年度報告以及 SEC 和 SEDAR 文件中列出的風險因素。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 不承擔修改或更新這些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。我現在將把電話轉給賴斯醫生。

Thank you, Susan. I want welcome everyone to our call for the third quarter ended September 30, 2023. Today, I first want to remind everyone that earlier this year, we knew we had an impressive lead agent, tuspetinib for the treatment of patients with AML. But we also had a limited cash runway to develop it. Strategically, we avoided any punitive financings and any potential warrant overhang, rather, we extended the cash runway with an at-the-market or ATM facility, with a committed equity facility, and through an investment by our partner, Hanmi Pharmaceutical. This was designed to give us breathing room and time to collect critical data with tuspetinib that may drive improved financing terms and potential collaborations.

謝謝你，蘇珊。歡迎大家參加我們截至2023 年9 月30 日的第三季度的電話會議。今天，我首先想提醒大家，今年早些時候，我們知道我們有一種令人印象深刻的主要藥物tuspetinib，用於治療AML患者。但我們開發它的現金管道也很有限。從策略上講，我們避免了任何懲罰性融資和任何潛在的認股權證過剩，相反，我們透過市場或ATM 設施、承諾股權設施以及我們的合作夥伴韓美製藥(Hanmi Pharmaceutical) 的投資來擴大現金跑道。這樣做的目的是為了給我們喘息的空間和時間來收集 tuspetinib 的關鍵數據，這可能會推動改善融資條件和潛在的合作。

We then undertook the APTIVATE expansion trial to understand tuspetinib's single agent activity and to identify relapsed or refractory AML populations with unmet need and who are particularly sensitive to our tuspetinib plus venetoclax or TUS/VEN doublet therapy.

然後，我們進行了APTIVATE 擴展試驗，以了解tuspetinib 的單藥活性，並確定需求未得到滿足的複發或難治性AML 人群以及對我們的tuspetinib 加維奈托克或TUS/VEN 雙聯療法特別敏感的人群。

We are in the tuspetinib as a single agent at our 80 milligram recommended Phase 2 dose. It is highly active in the patients naive to venetoclax with CR/CRh rates of 42% across all evaluable patients, 60% in FLT3-mutated patients, and nearly 30% in FLT3 wild-type patients, demonstrating potent single-agent activity across a breadth of patients. But we also observed that as we dose escalated above 80 milligrams to higher dose levels of tuspetinib as a single agent, the response rates unexpectedly dropped. Initially, we were unsure of what was driving this difference.

我們將 tuspetinib 作為單藥，建議的 2 期劑量為 80 毫克。它在未接受Venetoclax 治療的患者中具有高度活性，所有可評估患者的CR/CRh 率為42%，FLT3 突變患者為60%，FLT3 野生型患者為近30%，這表明單藥活性在所有可評估患者中均有效。患者的廣度。但我們也觀察到，當我們將 tuspetinib 單藥劑量增加到 80 毫克以上，達到更高劑量水平時，緩解率意外下降。最初，我們不確定是什麼導致了這種差異。

But after careful analysis, we learned that the patients entering the higher dose levels of 120 milligrams and above represented entirely different patient population. At that point in time, we transitioned above that 80 milligram dose. Certainly, more than 80% of the patients coming onto our trial had failed prior therapy with venetoclax. And these VEN failure AML patients are known to be far less responsive to salvage therapy. The VEN failure patients continue to respond to tuspetinib as a single agent, but at a lower response rate. So that mystery was solved.

但經過仔細分析，我們了解到進入 120 毫克及以上較高劑量水平的患者代表了完全不同的患者群體。那時，我們的劑量超過了 80 毫克。當然，超過 80% 參加我們試驗的患者之前接受維奈托克治療失敗。眾所周知，這些 VEN 失敗的 AML 患者對挽救治療的反應要差得多。 VEN 失敗患者繼續對 tuspetinib 作為單一藥物有反應，但反應率較低。於是這個謎團就解開了。

But more importantly, this rapidly emerging VEN failure population revealed a unique opportunity for tuspetinib. That's because tuspetinib targets to resistance mechanisms employed by AML to become resistant to venetoclax, which includes mutations in FLT3, KIT, JAK, and RAS pathways and increases in MCL1 expression.

但更重要的是，這一迅速出現的 VEN 失敗人群為 tuspetinib 提供了獨特的機會。這是因為 tuspetinib 靶向 AML 所採用的抗藥性機制，從而對 Venetoclax 產生抗藥性，其中包括 FLT3、KIT、JAK 和 RAS 途徑的突變以及 MCL1 表達的增加。

These VEN resistance mechanisms play directly into the targeting capabilities of tuspetinib, and suggested tuspetinib may resensitize then VEN failure patients to venetoclax, and that the tuspetinib venetoclax or TUS/VEN doublet may effectively treat this patient population in critical need of new therapies. And indeed, now we have learned that the TUS/VEN doublet is clearly active in relapsed or refractory VEN failure AML patients.

這些 VEN 抗藥性機制直接影響 tuspetinib 的靶向能力，並表明 tuspetinib 可能會使 VEN 失敗患者對 Venetoclax 重新敏感，並且 tuspetinib Venetoclax 或 TUS/VEN 雙藥可以有效治療急需新療法的此類患者群體。事實上，現在我們了解到 TUS/VEN 雙聯體在復發性或難治性 VEN 失敗 AML 患者中明顯具有活性。

In August of this year, we released our first data from 10 evaluable patients that have received the TUS/VEN doublet, 9 of you, who were VEN failures. The composite complete remission or CR rate was 44% among VEN failure patients, whether they were FLT3-mutated or FLT-3 wild type. That was impressive and we continued to enroll these VEN failure patients onto the TUS/VEN doublet.

今年 8 月，我們發布了 10 名接受 TUS/VEN 雙聯治療的可評估患者的第一份數據，其中 9 名患者是 VEN 失敗的患者。 VEN 失敗患者的複合完全緩解或 CR 率為 44%，無論他們是 FLT3 突變型還是 FLT-3 野生型。這令人印象深刻，我們繼續將這些 VEN 失敗患者納入 TUS/VEN 雙重治療。

We then released a second data cut in September, showing roughly the same composite CR rates among 15 evaluable patients. These data then generated tremendous investigator enthusiasm to place additional patients on the TUS/VEN doublet. By the time we reached our planned presentation at the European School of Hematology Conference last week, we had expected a total of up to 30 patients to have been dosed with the TUS/VEN doublet. But we actually have dosed 49 patients with the doublet, as of our data cut on October 23.

然後，我們在 9 月發布了第二次數據削減，顯示 15 名可評估患者的綜合 CR 率大致相同。這些數據隨後激發了研究者極大的熱情，將更多患者納入 TUS/VEN 雙聯治療。當我們上週在歐洲血液學院會議上進行規劃演講時，我們預計總共有多達 30 名患者接受了 TUS/VEN 雙聯治療。但截至 10 月 23 日截取的數據，我們實際上已對 49 名患者進行了雙重註射。

To be clear, many of these patients were very early in their course of treatment, just two to six weeks into the treatment in many cases. The composite CR rate at this point in time, with these early patients was about 29%, plus additional partial responses or PRs that emerged early to an overall response rate of 48%. While those early PRs are not yet CRs and are not counted in the composite CR rate, they are noteworthy.

需要明確的是，這些患者中的許多人處於治療的早期階段，在許多情況下僅接受治療兩到六週。此時，這些早期患者的綜合 CR 率約為 29%，加上早期出現的額外部分緩解或 PR，整體緩解率為 48%。雖然那些早期的 PR 還不是 CR，並且不計入綜合 CR 率，但它們值得注意。

For example, one patient entered the trial with a bone marrow blast count of 82% and dropped quickly to 7% after receiving the TUS/VEN doublet. That's a dramatic reduction in disease burden, but not quite below 5% in the bone marrow blast, so it's scored as a PR. We will continue to treat and watch such patients with the hope that many of these responses will mature to CRs over time.

例如，一名患者進入試驗時骨髓母細胞計數為 82%，但在接受 TUS/VEN 雙聯治療後迅速下降至 7%。這顯著降低了疾病負擔，但骨髓母細胞的疾病負擔並未低於 5%，因此被評為 PR。我們將繼續治療和觀察此類患者，希望隨著時間的推移，其中許多反應將成熟為 CR。

In fact, for all ongoing patients on the trial, we will continue to collect response maturation data and duration of response data. And to highlight our ability to execute this trial, we are approximately two quarters ahead of our expected enrollment rate in the APTIVATE trial, and that will allow us to watch for maturation of responses and extend the duration of response data earlier than we had expected, and to wrap up this trial up to two quarters earlier than we had expected.

事實上，對於所有正在進行試驗的患者，我們將繼續收集反應成熟數據和反應持續時間數據。為了強調我們執行這項試驗的能力，我們比APTIVATE 試驗的預期入組率大約提前了兩個季度，這將使我們能夠觀察反應的成熟情況，並比​​我們預期更早地延長反應數據的持續時間，並且比我們預期提前兩個季度結束這次試驗。

So what will we do with our findings? First, this sets us on the registrational path with the TUS/VEN doublet in relapsed or refractory VEN failure AML patients, inclusive of both FLT3-mutated and FLT3 wild-type patients. And that registrational study could begin in the second half of 2024 and potentially provide an accelerated approval pathway.

那我們將如何處理我們的發現呢？首先，這使我們走上了 TUS/VEN 雙聯體在復發或難治性 VEN 失敗 AML 患者（包括 FLT3 突變型和 FLT3 野生型患者）中的註冊之路。此註冊研究可能會在 2024 年下半年開始，並有可能提供加速審批途徑。

Second, data with the TUS/VEN doublet are segueing us into the tuspetinib/venetoclax/azacitidine triplet pilot study in front-line newly diagnosed AML patients. That study is planned to begin the first half of 2024, and the findings could then support a TUS/VEN/hypomethylating agent registrational trial in frontline AML. Tuspetinib has demonstrated potent activity across diverse AML groups with adverse mutations. It has a favorable safety and tolerability profile. It is convenient as a once daily oral tablet, and mechanistically targets the venetoclax resistance mechanism.

其次，TUS/VEN 雙聯體的數據促使我們在第一線新診斷的 AML 患者中進行 tuspetinib/venetoclax/azacitidine 三聯體試驗研究。該研究計劃於 2024 年上半年開始，研究結果可能支持 TUS/VEN/低甲基化劑在一線 AML 的註冊試驗。 Tuspetinib 在具有不良突變的不同 AML 群體中表現出有效的活性。它具有良好的安全性和耐受性。它作為每日一次的口服片劑很方便，並且在機制上針對 Venetoclax 抗藥性機制。

This makes tuspetinib an ideal drug for frontline combination therapy and for combination therapy in the relapsed or refractory AML population, particularly for the emerging wave of patients who failed venetoclax. In addition, the same properties of tuspetinib and its action on AML patients are leading us to include the treatment of patients with higher risk, MDS, and CMML in our trials going forward. We now are leveraging our clinical findings and plans to support financing and collaboration discussions. While we have no announcements to make and can make no commitments in these regards, we clearly are pursuing these paths.

這使得 tuspetinib 成為一線聯合治療和復發或難治性 AML 族群聯合治療的理想藥物，特別是對於新出現的維奈托克失敗患者。此外，tuspetinib 的相同特性及其對 AML 患者的作用促使我們在未來的試驗中納入對高風險、MDS 和 CMML 患者的治療。我們現在正在利用我們的臨床發現和計劃來支持融資和合作討論。雖然我們在這些方面沒有發布任何公告，也無法做出任何承諾，但我們顯然正在走這些道路。

I now want to turn the call over to Dr. Bejar, our Chief Medical Officer and resident KOL for his insights and comments on our latest data. Raf?

現在我想將電話轉給我們的首席醫療官兼駐場 KOL Bejar 博士，請他對我們的最新數據提出見解和評論。拉夫？

Thank you, Bill. I first want to highlight our latest news. We announced last week that clinical data for tuspetinib or TUS has been selected for an oral presentation at the ASH meeting in December, which will be given by our lead investigator, Dr. Naval Daver of the MD Anderson Cancer Center. Dr. Daver will present data from Aptose's ongoing Phase 1/2 APTIVATE trial tuspetinib in relapsed/refractory patients with acute myeloid leukemia. We're really pleased by this recognition from our esteemed colleagues and look forward to sharing the APTIVATE data in this forum.

謝謝你，比爾。我首先想強調一下我們的最新消息。我們上週宣布，tuspetinib 或 TUS 的臨床數據已選擇在 12 月的 ASH 會議上進行口頭報告，該報告將由我們的首席研究員、MD 安德森癌症中心的 Naval Daver 博士提供。 Daver 博士將介紹 Aptose 正在進行的 1/2 期 APTIVATE 試驗 tuspetinib 在復發/難治性急性髓性白血病患者中的數據。我們對尊敬的同事的認可感到非常高興，並期待在本論壇中分享 APTIVATE 數據。

As Bill mentioned, just over a week ago, during the European School of Hematology meeting on AML or ESH, we reviewed all the data to-date from an October 23 data cut from the TUS APTIVATE trial. We're not going to go through a full data rehash here, we will make this call efficient. But I just want to clarify some key points, address the misperceptions, and answer some of the questions that we've been getting over the last week or so. If you did not listen to our ESH call, I encourage you to do so, and you can access it on our website under the events tab.

正如 Bill 所提到的，就在一周前，在歐洲血液學院關於 AML 或 ESH 的會議上，我們審查了 10 月 23 日從 TUS APTIVATE 試驗中截取的數據中迄今為止的所有數據。我們不會在這裡進行完整的資料重新哈希，我們將使此呼叫更加有效率。但我只是想澄清一些關鍵點，消除誤解，並回答我們在過去一周左右提出的一些問題。如果您沒有收聽我們的 ESH 電話會議，我鼓勵您這樣做，您可以在我們網站的「活動」標籤下訪問它。

Dr. Daver joined us on the ESH call last week as an internationally recognized expert in the development of clinical therapeutics for AML, including combination therapies. It was extremely helpful to get his impressions of the ongoing needs in AML and how tuspetinib could help address them.

Daver 博士上週作為國際公認的 AML 臨床療法（包括聯合療法）開發專家參加了我們的 ESH 電話會議。了解 AML 的持續需求以及 tuspetinib 如何幫助解決這些需求非常有幫助。

One of the things we discussed is the changing AML patient population and emerging needs in the AML treatment landscape. The vast majority of US AML -- US-based AML patients entering clinical trials now have tried and were failed by venetoclax at some point in the course of their disease. In our APTIVATE trial, the percentage of US-based patients who have failed venetoclax has grown to about 90%. These are patient population with highly resistant mutation patterns and dismal response rates to salvage therapy, the CR rates often in the single digits, whether treated with monotherapies or drug combinations.

我們討論的事情之一是不斷變化的 AML 患者群體和 AML 治療領域的新需求。目前，絕大多數進入臨床試驗的美國 AML 患者都曾嘗試過 Venetoclax，但在疾病過程中的某個階段都失敗了。在我們的 APTIVATE 試驗中，美國 Venetoclax 失敗的患者比例已增加至約 90%。這些患者族群具有高度抗藥性的突變模式，對挽救治療的反應率很低，無論是單一療法還是藥物組合治療，CR 率通常只有個位數。

This extremely challenging patient population with a rapidly emerging medical need is what all of us were trying to develop AMR treatments, relapse refractory populations are up against. We're seeing an entirely different group of patients than drugs that were developed just a few years ago. indeed, what we are seeing in the APTIVATE expansion trial, the majority of patients have failed prior therapies venetoclax and have unmuted FLT3 AML, a patient population that accounts for an estimated 70% of AML cases. And with few or no effective treatment options being able to potentially target the larger FLT3 unmutated patient population, and to do so safely is a key differentiator for tuspetinib.

我們所有人都在努力開發抗微生物藥物抗藥性治療方法，而復發難治性族群所面臨的挑戰是醫療需求迅速增長的極具挑戰性的患者群體。我們看到的患者群體與幾年前開發的藥物完全不同。事實上，我們在 APTIVATE 擴展試驗中看到，大多數患者先前的 Venetoclax 治療均失敗，並且患有未抑制的 FLT3 AML，這一患者群體估計佔 AML 病例的 70%。由於很少或沒有有效的治療方案能夠潛在地針對更大的 FLT3 未突變患者群體，並且安全地做到這一點是 tuspetinib 的關鍵差異化因素。

And for people who shake their heads because there's so much going on in AML and it's difficult to determine the potential winners in this space, it's important to note that tuspetinib is differentiated by its clinical activity in the FLT3 unmutated population. So the positive data we've generated for tuspetinib which includes responses in that FLT3 unmutated or wild-type AML makes it that much more exciting. And there is room for many other AML drugs in development too.

對於因 AML 領域發生的事情太多而搖頭的人來說，很難確定該領域的潛在贏家，重要的是要注意 tuspetinib 因其在 FLT3 未突變人群中的臨床活性而與眾不同。因此，我們為 tuspetinib 產生的正面數據（包括 FLT3 未突變或野生型 AML 的反應）使其更加令人興奮。許多其他 AML 藥物也有開發空間。

AML is an extremely heterogeneous disease with broadly resistant mutation patterns that will take combination therapies of drugs targeting different kinases of other pathways to manage the disease across different populations.

AML 是一種極其異質的疾病，具有廣泛的抗藥性突變模式，需要採用針對其他途徑的不同激酶的藥物聯合療法來控制不同人群的疾病。

As we get into review of our data highlights, I want to give a quick explanation of what we mean by evaluable patients as it's defined in our protocol. Briefly, we consider evaluable any patient that has reached their second response assessment at the end of cycle one or has had an objective response at their first response assessment.

當我們回顧我們的數據要點時，我想快速解釋一下我們的方案中定義的可評估患者的含義。簡而言之，我們認為在第一周期結束時達到第二次反應評估或在第一次反應評估時獲得客觀反應的任何患者都是可評估的。

Participants that discontinue treatment for disease progression after that first reassessments are in fact, considered evaluable. Only patients who don't undergo a response assessment or have stable disease with less than one cycle of treatment are considered not evaluable or technically inevaluable. Currently, about 85% of our study participants are considered evaluable by the end of cycle one. But we also have several ongoing patients that have not yet reached this milestone and will do so in the coming weeks.

事實上，在第一次重新評估後因疾病進展而停止治療的參與者被認為是可評估的。只有未接受療效評估或治療時間少於一個週期病情穩定的患者才被認為不可評估或在技術上無法評估。目前，我們約有 85% 的研究參與者在第一周期結束時被認為可以進行評估。但我們還有幾名正在治療的患者尚未達到這一里程碑，並將在未來幾週內達到這一里程碑。

For example, in our latest data cut, it was 31 evaluable patients out of the 49 patients dosed with the TUS/VEN doublet, many have very recently entered the trial and have only just finished one cycle of treatment with tuspetinib having been dosed in September and October, with many patients pending evaluability assessment in the next two to three weeks. Data reported at ESH are therefore early. We expect more of the responses to continue to mature. We will have more evaluable patients over time, including next month at ASH when we'll provide another update.

例如，在我們最新的數據統計中，接受 TUS/VEN 雙藥治療的 49 名患者中有 31 名可評估患者，其中許多患者最近才進入試驗，並且剛剛完成 9 月份服用的 tuspetinib 的一個週期治療十月份，許多患者將在接下來的兩到三週內等待可評估性評估。因此，ESH 報告的數據還為時過早。我們預計更多的回應將繼續成熟。隨著時間的推移，我們將有更多可評估的患者，包括下個月在 ASH 上我們將提供另一次更新。

A quick note on patient enrollment. As of today, more than 150 patients have been treated with this tuspetinib, 91 patients have received tuspetinib as a single agent. And as Bill said, we have anticipated dosing up to 30 patients with TUS/VEN while the ESH 2023 conference. However, due to investigator enthusiasm, we ended up with more than 49 patients as of October 23, and patients continue being enrolled.

關於患者登記的快速說明。截至目前，已有超過 150 名患者接受了 tuspetinib 的治療，其中 91 名患者接受了 tuspetinib 單藥治療。正如 Bill 所說，我們預計在 ESH 2023 會議期間對多達 30 名患者進行 TUS/VEN 給藥。然而，由於研究者的熱情，截至 10 月 23 日，我們最終招募了超過 49 名患者，且患者仍在繼續入組。

Now let's talk about the safety profile. In the most recent data cut from October 23, the favorable safety profile remained consistent for TUS and TUS/VEN treated relapse/refractory AML patients, with no new or unexpected safety signals noted. We've reviewed the safety profile of tuspetinib often, so I'll keep it brief here.

現在我們來談談安全性。在 10 月 23 日的最新數據中，TUS 和 TUS/VEN 治療的複發/難治性 AML 患者的良好安全性保持一致，沒有發現新的或意外的安全訊號。我們經常審查 tuspetinib 的安全性，因此我將在這裡簡單介紹一下。

In short, tuspetinib continues to avoid many of the typical toxicities observed with other agents, including FLT3, IDH1/2, and menin inhibitors such as QTc prolongation, differentiation syndrome, and elevations of muscle enzymes like CBK that are related to treatment. We have not observed these as a clinical concern in our treatment.

簡而言之，tuspetinib 繼續避免了其他藥物觀察到的許多典型毒性，包括 FLT3、IDH1/2 和 menin 抑制劑，如 QTc 延長、分化症候群和與治療相關的肌肉酶（如 CBK）升高。我們在治療中尚未觀察到這些作為臨床問題。

Some quick highlights of the data we presented at ESH AML meeting regarding tuspetinib as a single agent. tuspetinib as a single agent was well-tolerated and highly active on relapse or refractory AML patients with a diversity of genotypes. TUS single-agent delivery 42% and 60% CR/CRh response rates across all patients and across FLT3-mutated patients respectively. And among in the evaluable VEN naive patient population treated at 80 milligrams, they recommended Phase 2 dose for tuspetinib.

我們在 ESH AML 會議上提供的關於 tuspetinib 作為單一藥物的數據的一些快速亮點。托培替尼作為單藥，對具有多種基因型的複發或難治性 AML 患者俱有良好的耐受性和高度活性。 TUS 單藥給藥對所有患者和 FLT3 突變患者的 CR/CRh 反應率分別為 42% 和 60%。在接受 80 毫克治療的可評估 VEN 初治患者群體中，他們推薦 tuspetinib 的 2 期劑量。

Tuspetinib demonstrated a 29% CR/CRh rate in VEN naive FLT3 unmuted or wild-type patients at this 80 milligram RP2D dose. This unlocks the potential for tuspetinib to treat an additional 70% to 75% of the AML population without the FLT3 mutation that is not currently addressed by any approved tyrosine kinase inhibitor. Tuspetinib single-agent response rates compare favorably to gilteritinib and match patient populations. Details on this interesting comparison are presented in our slide deck from the meeting, which is available on our website.

在 80 毫克 RP2D 劑量下，Tuspetinib 在未經 VEN 治療的 FLT3 未突變或野生型患者中顯示出 29% 的 CR/CRh 率。這釋放了 tuspetinib 治療另外 70% 至 75% 沒有 FLT3 突變的 AML 族群的潛力，目前任何批准的酪胺酸激酶抑制劑都無法解決這種突變。 Tuspetinib 單藥反應率優於 gilteritinib，並且與患者群體相符。有關此有趣比較的詳細資訊在我們的會議幻燈片中提供，該幻燈片可在我們的網站上找到。

Let's turn to the doublet data. In addition to the safety and efficacy of tuspetinib at we reported at ESH, we also presented a poster that were in points mentioned here. Tuspetinib directly targets pathways involved in VEN resistance. By shutting down these pathways, tuspetinib appears to clinically resensitize prior VEN failure patients to venetoclax. Our overall response rates with the TUS/VEN doublet includes several recent preliminary responses. And as of last week, we had dosed 49 patients, 31 of whom were evaluable to date. Keen investigator interest has led to this increased rate of enrollment, and we expect to report an additional patients at ASH in December.

讓我們轉向雙峰數據。除了我們在 ESH 上報導的 tuspetinib 的安全性和有效性外，我們還展示了此處提到的要點的海報。 Tuspetinib 直接針對參與 VEN 抗藥性的途徑。透過關閉這些途徑，tuspetinib 似乎可以在臨床上使先前 VEN 失敗的患者對 Venetoclax 重新敏感。我們對 TUS/VEN 雙聯體的整體回覆率包括最近的一些初步回覆。截至上週，我們已對 49 名患者進行了給藥，其中 31 人迄今為止可進行評估。研究者的強烈興趣導致了入組率的增加，我們預計 12 月在 ASH 報告更多患者。

Our evaluable patients showed an overall response rate of 48% at 15 out of the 31 evaluable patients. 81% or 25 out of 31 evaluable patients were prior VEN failures. 44% overall response rate was observed in the VEN failure population. There was a 60% overall response rate in the FLT3-mutant population in a 43 overall response rate in the FLT3 unmutated population. As I mentioned, most patients are early in the course of treatment, having initiated dosing in the past two to six weeks, we do expect these responses to mature over time.

在 31 名可評估患者中，有 15 名可評估患者的整體緩解率為 48%。 81%（即 31 名可評估患者中的 25 名）之前曾經歷過 VEN 失敗。在 VEN 失敗族群中觀察到 44% 的整體緩解率。 FLT3 突變族群的整體緩解率為 60%，FLT3 未突變族群的整體緩解率為 43%。正如我所提到的，大多數患者處於治療過程的早期，在過去兩到六週內開始給藥，我們確實預計這些反應會隨著時間的推移而成熟。

Our experience with the TUS/VEN doublet will inform how best to carry out the triple combination with the TUS/HMA/venetoclax in the frontline setting. In the near term, we continue to collect data to demonstrate that the doublet is active in patients who have prior venetoclax exposure, both with and without the FLT3 mutation, and to meet and share with potential partners, how we might be able to position tuspetinib for frontline triplet therapy and maintenance therapy, and move tuspetinib and Aptose onto a clear path for success.

我們在 TUS/VEN 雙聯劑方面的經驗將告訴我們如何在前線環境中最好地與 TUS/HMA/venetoclax 進行三重組合。在短期內，我們將繼續收集數據，以證明雙聯體在既往接受過 Venetoclax 治療的患者中具有活性，無論是否有 FLT3 突變，並與潛在合作夥伴會面並分享我們如何定位 tuspetinib用於一線三聯療法和維持治療，並使tuspetinib 和Aptose 走上一條清晰的成功之路。

Indeed, tuspetinib with its proven breadth of activity and safety profile may address the most sizable markets in AML, and we are developing it as such. The interest in tuspetinib from potential partners continues to grow. And we are engaged in multiple productive discussions, because tuspetinib looks like large biotech or big pharma drug. Therefore, we endeavor to design our patient grows to meet the needs of Aptose, meet the needs of regulatory agencies, and to meet the desires of potential partners.

事實上，tuspetinib 以其經過驗證的廣泛活性和安全性可能會滿足 AML 中最大的市場，我們正在開發它。潛在合作夥伴對 tuspetinib 的興趣持續增長。我們正在進行多次富有成效的討論，因為 tuspetinib 看起來像大型生物技術或大型製藥藥物。因此，我們努力設計我們的患者生長以滿足 Aptose 的需求，滿足監管機構的需求，並滿足潛在合作夥伴的願望。

We look forward to sharing more at the upcoming ASH conference, and we're very pleased that TUS clinical data was recognized and selected for an oral presentation by Dr. Daver. We will also plan on releasing our next set of updated data at the time.

我們期待在即將舉行的 ASH 會議上分享更多信息，我們很高興 TUS 臨床數據得到認可並被 Daver 博士選擇進行口頭報告。我們也計劃屆時發布下一組更新資料。

As Dr. David described in the question-and-answer session after our clinical update call at ESH, the safety and efficacy data that we're seeing with the tuspetinib/venetoclax combination is very encouraging, and suggests that TUS may effectively treat the growing number of VEN failures that we're seeing in relapse/refractory AML.

正如 David 博士在 ESH 臨床更新電話會議後的問答環節中所描述的那樣，我們看到的 tuspetinib/venetoclax 組合的安全性和有效性數據非常令人鼓舞，並表明 TUS 可以有效治療生長中的癌症。我們在復發/難治性AML 中看到的VEN 失敗數。

We're now looking forward to moving TUS forward into a tuspetinib/venetoclax/azacitidine triplet for the treatment of frontline newly diagnosed AML patients. Tuspetinib safety profile is key here. We believe that it has the potential to be the ideal drug for combination therapy in AML, both in the frontline and in the relapse/refractory settings.

我們現在期待將 TUS 發展為 tuspetinib/venetoclax/azacitidine 三聯療法，用於治療一線新診斷的 AML 患者。 Tuspetinib 的安全性是關鍵。我們相信，它有潛力成為 AML 聯合治療的理想藥物，無論是在一線治療還是在復發/難治性治療中。

So to sum up our timelines and milestones. We (technical difficulty) trial, we will report data when available at appropriate forums. As we discussed in our last call, we plan to present an extended (technical difficulty) TUS/VEN doublet arm at ASH in December. Also, during the fourth quarter this year, we expect to provide additional color around our registrational plans of tuspetinib. Also, the (technical difficulty) conferences and earnings calls. So we have much to consider and deliberate as we go forward.

總結一下我們的時間表和里程碑。我們（技術難度）試驗，我們將在適當的論壇上報告可用的數據。正如我們在上次電話會議中討論的那樣，我們計劃在 12 月的 ASH 上展示擴展的（技術難度）TUS/VEN 雙臂。此外，在今年第四季度，我們預計將圍繞我們的 tuspetinib 註冊計劃提供更多資訊。此外，還有（技術難度）會議和收益電話會議。因此，在前進的過程中，我們有很多事情需要考慮和深思熟慮。

Now I'd like to turn the call over to our CFO, Fletcher Payne for an update on our financial status. Fletcher?

現在我想將電話轉給我們的財務長 Fletcher Payne，以了解我們財務狀況的最新情況。弗萊徹？

(technical difficulty)

（技術難度）

Hello, everyone, for some reason we are unable to hear Fletcher. So I am going to jump in at this point, and I apologize.

大家好，由於某些原因我們聽不到弗萊徹的聲音。所以我現在要插話，並表示歉意。

I'd like to start by noting that in addition to our comments on this call, additional information may be found in today's press release and the 10-Q filed with the SEC. As discussed in our financial statements, the company plans to raise additional funds to fund business operations. During the 2023, we used the 2022 ATM facility, the 2023 committed equity facility, and the Hanmi subscription agreement to raise capital. We continue to use these methods to raise capital, and we are also actively evaluating other options to raise capital, including debt, equity issuance, and corporate collaborations.

首先我想指出，除了我們對本次電話會議的評論之外，還可以在今天的新聞稿和向 SEC 提交的 10-Q 中找到更多資訊。正如我們的財務報表中所討論的，該公司計劃籌集額外資金來為業務運營提供資金。在2023年期間，我們使用2022年ATM融資、2023年承諾股權融資和Hanmi認購協議來籌集資金。我們將繼續使用這些方法來籌集資金，同時我們也積極評估其他籌集資金的選擇，包括債務、股票發行和企業合作。

Lastly, we continue to evaluate ways to reduce operational expenses. Based on current operations, the company expects that cash on hand plus available capital from Hanmi subscription agreements, committed equity facility, and the ATM facility provide the company with sufficient resources to fund planned company operations, including research and development through March of 2024. I will direct you to also review the company's risk factors and the discussion in the going concern footnote in our 10-Q.

最後，我們繼續評估減少營運費用的方法。根據目前的營運情況，公司預計手頭現金加上來自 Hanmi 認購協議、承諾股權融資和 ATM 融資的可用資本，將為公司提供足夠的資源來資助公司計劃運營，包括截至 2024 年 3 月的研發。將引導您查看公司的風險因素以及我們10-Q 中持續經營腳註中的討論。

Now let's review the third quarter of 2023 financials. We continue our disciplined financial management of our operations and prioritization of our investments in the tuspetinib clinical program. We ended the third quarter of 2023 with approximately $17.7 million in cash, cash equivalents, and investments, a decrease of approximately $5.6 million as compared to June 30, 2022. The $5.6 million decrease in cash and investments as a result of the use of funds for the APTIVATE study and operating expenses, which was offset by an increase in cash from financing activities.

現在讓我們回顧一下 2023 年第三季的財務狀況。我們繼續對我們的營運進行嚴格的財務管理，並優先考慮對 tuspetinib 臨床項目的投資。截至 2023 年第三季末，我們的現金、現金等價物和投資約為 1,770 萬美元，比 2022 年 6 月 30 日減少約 560 萬美元。由於資金使用，現金和投資減少了 560 萬美元用於APTIVATE研究和營運費用，該費用被融資活動現金的增加所抵消。

On a cumulative basis through September 30, 2023, the company has raised a total of $6.1 million, $3 million from the Hanmi subscription agreement, $1.9 million gross proceeds from the 2022 ATM facility, and $1.2 million gross proceeds from the 2023 committed equity facility.

截至2023 年9 月30 日，該公司已累計籌集610 萬美元，其中300 萬美元來自Hanmi 認購協議，來自2022 年ATM 融資的總收益為190 萬美元，來自2023 年承諾股權融資的總收益為120萬美元。

During the quarter, the net loss was approximately $11.4 million, translating into approximately $1.76 per share, first loss per share compared to $9.8 million or $1.59, $1.59 loss per share from the same period in 2022. As of November 9, 2023, Aptose has 7,806,923 common shares outstanding. All the references to loss per share and shares outstanding have been presented to reflect the 1 for 15 reverse stock split completed on June 6, 2023.

本季淨虧損約1,140 萬美元，相當於每股約1.76 美元，首次每股虧損，而2022 年同期為980 萬美元或1.59 美元，每股虧損1.59 美元。截至2023 年11 月9 日，Aptose已7,806,923 股已發行普通股。所有提及每股虧損和已發行股票的內容均已列出，以反映 2023 年 6 月 6 日完成的 15 股反向股票分割。

As seen in the income statement, we had no revenue during the first nine months of 2023. Research and development expenses were approximately $8.3 million for the quarter, compared to $6.6 million during the same quarter of 2022. Program cost for tuspetinib were $5.8 million for the three months ended September 30, 2023, compared to $3 million for the three months ended September 30, 2022. Our program for tuspetinib in the current period represents the enrollment of patients in our APTIVATE clinical trial, clinical materials to healthy volunteer trial that we've completed, and other expenses.

從損益表中可以看出，我們在2023 年前9 個月沒有收入。該季度的研發費用約為830 萬美元，而2022 年同一季度的研發費用為660 萬美元。tuspetinib 的專案成本為580 萬美元。截至2023 年9 月30 日的三個月，而截至2022 年9 月30 日的三個月為300 萬美元。我們本期的tuspetinib 計劃代表了我們APTIVATE 臨床試驗的患者入組、健康志願者試驗的臨床材料，已完成，及其他費用。

Program costs luxeptinib were $648,000 for the three months ended September 30, 2023, and decreased by approximately $742,000 compared to $1.4 million for the three months ended September 30, 2022, primarily due to lower clinical trial cost and lower manufacturing costs as a result of the current G3 formulation, which required less API, our active pharmaceutical ingredient than the prior formulation.

截至2023年9月30日止三個月，luxeptinib的專案成本為648,000美元，與截至2022年9月30日止三個月的140萬美元相比，減少約742,000美元，主要是由於臨床試驗成本和製造成本降低，目前的 G3 配方，與先前的配方相比，需要更少的 API（我們的活性藥物成分）。

G&A expenses were $3.4 million for the quarter, compared to $3.5 million from the same quarter of 2020. The decrease is primarily due to lower stock-based compensation, partially offset by increased salary expenses and higher professional fees.

本季的一般管理費用為 340 萬美元，而 2020 年同季為 350 萬美元。減少的主要原因是股票薪酬減少，但部分被工資費用增加和專業費用增加所抵消。

We now would like to open the call for questions. And please do feel free to pose questions to any of us. So operator, if you could please introduce the questions.

我們現在要開始提問。請隨時向我們任何人提出問題。接線員，如果可以的話請介紹一下問題。

(Operator Instructions)

（操作員說明）

John Newman, Canaccord Genuity.

約翰紐曼，Canaccord Genuity。

Hi, guys. Thanks for taking my question. Sorry, there is some noise in the background.

嗨，大家好。感謝您提出我的問題。抱歉，背景中有一些噪音。

No problem.

沒問題。

I am just curious here, I know that earlier in the study, there were a lot of patients that were doing very well on tuspetinib and those patients were able to go to transplant. And I'm curious if the mechanism by which that can occur is the same. So are physicians still able to sort of make whatever call that they believe is in the patient's best interest, and say this patient should go to transplant? Or is there anything different about the study at this point in time, especially for the doublet? Thanks.

我只是很好奇，我知道在研究的早期，有很多患者在 tuspetinib 上表現良好，並且這些患者能夠接受移植。我很好奇發生這種情況的機制是否相同。那麼，醫生是否仍然能夠做出他們認為符合患者最大利益的任何決定，並說該患者應該接受移植？或者說目前的研究有什麼不同，特別是對於雙峰？謝謝。

Okay. So, John, the earlier patients you were talking about were on the single agent tuspetinib, and now we're primarily talking about the TUS/VEN doublet. And I'm going to ask Dr. Bejar to address that, please.

好的。所以，約翰，您所說的早期患者使用單藥 tuspetinib，現在我們主要談論 TUS/VEN 雙藥。我將請 Bejar 博士解決這個問題。

Sure. Yeah, so I think I understand the question. So you're correct that we had several patients go to transplant in the single agent portion of the study. And the rules haven't changed. The physicians can continue to do whatever is in the best interest of the patient. We would encourage them to take the patients to transplant if it is an option.

當然。是的，所以我想我理解這個問題。所以你是對的，我們有幾位患者在研究的單藥部分進行了移植。而且規則沒有改變。醫生可以繼續做任何符合病人最大利益的事情。如果可以的話，我們鼓勵他們帶病人去移植。

We are hoping that the ability to reduce their blast count and reduce their disease burden might allow more patients to go to transplant than would otherwise. But as we said in the call, it is still early. So the decisions about transplant are likely not made yet and many of these patients that have just started the study are at least a couple or two months.

我們希望，減少原始細胞計數和減輕疾病負擔的能力可能會讓更多的患者接受移植。但正如我們在電話中所說，現在還為時過早。因此，有關移植的決定可能尚未做出，許多剛開始研究的患者至少已經有幾個月或兩個月了。

John, does that answer your question? is there anything else?

約翰，這能回答你的問題嗎？還有別的事嗎？

It does, that does answer my question. Thank you.

確實如此，這確實回答了我的問題。謝謝。

All right. Thank you, John.

好的。謝謝你，約翰。

Gregory Renza, RBC Capital Markets.

格雷戈里·倫扎（Gregory Renza），加拿大皇家銀行資本市場部。

Hi, Bill and team. It's Anish on for Greg. Congrats on the quarter and thanks for taking my questions. Just firstly, on the expansion to high-risk MDS and CMML for tuspetinib, what aspects of the data to-date give confidence on this sort of this expansion opportunity? How should we be thinking about mechanistic overlap? And then, just when thinking about the sort of progression and development for tuspetinib, how should we be thinking about resource allocation and any considerations for collaborative opportunities in these ventures? Congrats on the progress and thanks again.

嗨，比爾和團隊。格雷格的安尼什上場了。恭喜本季度，感謝您提出我的問題。首先，關於 tuspetinib 向高風險 MDS 和 CMML 的擴展，迄今為止數據的哪些方面讓我們對這種擴展機會充滿信心？我們應該如何考慮機械重疊？那麼，在思考 tuspetinib 的進展和發展時，我們應該如何考慮這些企業的資源分配和合作機會？恭喜您取得的進展，並再次表示感謝。

So I'm going to talk to Bejar to address the first part of that, that fits right into his expertise in the high-risk MDS. Raf?

因此，我將與 Bejar 討論第一部分，這正好符合他在高風險 MDS 方面的專業知識。拉夫？

Yeah, thanks, for that question. So the higher-risk MDS patients, particularly those patients that have increased blasts in the bone marrow, that are just shy in that AML threshold, a very similar pathophysiological and unfortunately, very similar outcomes to patients with frank AML. In fact, the ICC, the International Classification Consortium committee recently redesignated these patients with more than 10% blasts as being MDS/AML because of the shared physiology and outcome.

是的，謝謝你提出這個問題。因此，高風險 MDS 患者，特別是那些骨髓中原始細胞增加的患者，其 AML 閾值略顯不足，與患有明顯 AML 的患者的病理生理學非常相似，不幸的是，結果也非常相似。事實上，由於共同的生理學和結果，ICC（國際分類聯盟委員會）最近將這些原始細胞超過 10% 的患者重新指定為 MDS/AML。

What we've observed in our study is that we have several FLT3 unmutated patients that have very MDS like mutation patterns, mutations and things like splicing factors, genes like ASXL1, types of mutations that we associate with AML with myelodysplasia related changes. So this is the clinical rationale for extending the treatment of tuspetinib into this very AML like MDS population.

我們在研究中觀察到，我們有幾位 FLT3 未突變患者，他們具有非常 MDS 的突變模式、突變以及剪接因子、ASXL1 等基因、我們將其與 AML 和骨髓增生異常相關變化相關的突變類型。因此，這就是將 tuspetinib 治療擴展到這個非常類似 AML 的 MDS 族群的臨床理由。

CMML also share some of these pathophysiological features, but also have a very proliferative phenotype with regard to the monocytes that give the disease its name. And we think that the particular axis of activity for tuspetinib might be particularly favorable in that patient population. We don't want to exclude them from this potential benefit till we know that there aren't that many of them out there. And we hope that we get a few in our trials, so we can at least explore the activity in this really underserved patient population.

CMML 也具有一些病理生理學特徵，但也具有單核細胞高度增殖的表型，這也是該疾病的名稱。我們認為 tuspetinib 的特定活性軸可能對該患者群體特別有利。我們不想將它們排除在這種潛在好處之外，直到我們知道它們的數量並不多。我們希望在試驗中得到一些結果，這樣我們至少可以在這個真正服務不足的患者群體中探索這項活動。

Okay, I'll take on the next part. So regarding the MDS patients, as Dr. Bejar said, there is a need. There is also a great deal of larger pharmas, larger biotech companies who are interested in seeing data in those patients, because it can represent a large commercial opportunity. Regarding the resource allocation, currently, we are the TUS in doublet study with patients. As I said, those patients have been accruing very rapidly, and we expect to be able to tidy up that the trial of probably 1.5 to 2 quarters earlier than expected.

好的，我來接下一部分。所以對於MDS患者，正如Bejar醫師所說，是有必要的。還有很多大型製藥公司、大型生技公司有興趣查看這些患者的數據，因為它代表著巨大的商業機會。關於資源分配，目前我們正在與患者進行雙重研究中的TUS。正如我所說，這些患者的數量增長得非常快，我們預計能夠比預期提前 1.5 到 2 個季度完成試驗。

So in terms of our next top priorities for how we're going to allocate the resources, the next one is -- the next top priority is the triplet, the VEN -- the TUS/VEN/HMA triplet. It's the pilot study in, say, 20 to 40 patients. There's tremendous interest in driving this drug to the frontline newly diagnosed patients, and we'd like to get data there as quickly as possible.

因此，就我們如何分配資源的下一個首要任務而言，下一個是－下一個首要任務是三元組，VEN－TUS/VEN/HMA 三元組。這是一項針對 20 至 40 名患者的試驗研究。人們對將這種藥物推向第一線新診斷患者抱持極大興趣，我們希望盡快獲得數據。

The next priority then would be the MDS CMML patients. Again, tremendous interest from a variety of additional resources outside of our company that are interested in that patient population. Beyond that, then we would look to the registrational trials that could then start. The first would begin in the doublet patients, so that was the TUS/VEN. And the relapsed/refractory patients who have failed venetoclax previously. And then after that would be the triplet, the registration trial for the triplet and frontline newly diagnosed patients. So did that -- Anish, thanks for the question. Did that answer it?

下一個優先事項將是 MDS CMML 患者。同樣，我們公司外部對患者群體感興趣的各種其他資源也表現出了極大的興趣。除此之外，我們將考慮隨後開始的註冊試驗。第一個將從雙聯體患者開始，即 TUS/VEN。以及先前使用維奈托克失敗的復發/難治性患者。然後就是三聯體，三聯體和第一線新確診患者的註冊試驗。也是如此——Anish，謝謝你的提問。這樣回答了嗎？

Yes, great. Thanks so much for the color.

對，很好。非常感謝你的顏色。

Okay. Thanks for being here today.

好的。感謝您今天來到這裡。

(Operator Instructions) I'm currently showing no further questions. I will now turn the call back to Dr. Rice for closing remarks.

（操作員說明）我目前沒有顯示任何其他問題。現在我將把電話轉回給賴斯博士，讓其致閉幕詞。

Okay. Thank you so much, folks. Also, want to thank everyone for joining us this afternoon. As you can tell, we're really excited about the growing body of safety and efficacy data on tuspetinib and the tuspetinib/venetoclax combination in these very difficult to treat patient populations of AML. We believe tuspetinib can improve upon the standard of care for AML patients that are currently imperfectly served by the current therapies.

好的。非常感謝你們，夥伴們。另外，要感謝大家今天下午加入我們。如您所知，我們對 tuspetinib 和 tuspetinib/venetoclax 組合在這些非常難以治療的 AML 患者群體中的安全性和有效性數據不斷增長感到非常興奮。我們相信 tuspetinib 可以改善 AML 患者的照護標準，而目前的治療方法尚無法完全滿足這些患者的需求。

As always, we thank our patients, investigators, and employees for their important role in this effort. Our clinical team has been key in ramping up the enrollment in the APTIVATE trial and collecting data for our latest data cut. And I continue to recognize them for their execution. We appreciate our shareholders and analysts who continue to support us, and we look forward to keeping you updated on our progress. I want to thank all of you and have a wonderful evening. Take care, bye-bye.

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。我們的臨床團隊在增加 APTIVATE 試驗的入組人數和收集最新數據削減的數據方面發揮了關鍵作用。我繼續認可他們的執行力。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的最新進展。我要感謝大家並祝您有個美好的夜晚。保重，再見。

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。