Curis Inc (CRIS) 2022 Q4 法說會逐字稿

Good morning, and welcome to the Curis Fourth Quarter 2022 Business Update Call. (Operator Instructions) Please note, this event is being recorded. I would now like to turn the conference over to Diantha Duvall, Curis' Chief Financial Officer. Diantha, please go ahead.

早上好，歡迎來到 Curis 2022 年第四季度業務更新電話會議。 （操作員說明）請注意，正在記錄此事件。我現在想將會議轉交給 Curis 的首席財務官 Diantha Duvall。黛安莎，請繼續。

Thank you, and welcome to the Curis Fourth Quarter 2022 Business Update Call. Before we begin, I would like to encourage everyone to go to the Investors section of our website at www.curis.com to find our fourth quarter 2022 business update release and related financial tables.

謝謝，歡迎參加 Curis 2022 年第四季度業務更新電話會議。在我們開始之前，我想鼓勵大家訪問我們網站 www.curis.com 的投資者部分，找到我們 2022 年第四季度業務更新發布和相關財務表格。

I would also like to remind everyone that during the call, we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and actual results may differ materially. For additional details, please see our SEC filings.

我還想提醒大家，在電話會議期間，我們將根據我們目前的預期和信念做出前瞻性陳述。這些陳述受某些風險和不確定因素的影響，實際結果可能存在重大差異。有關更多詳細信息，請參閱我們向美國證券交易委員會提交的文件。

Joining me on today's call are Jim Dentzer, President and Chief Executive Officer; and Bob Martell, Head of R&D. We will also be available for a question-and-answer period at the end of the call.

與我一起參加今天電話會議的還有總裁兼首席執行官 Jim Dentzer；和研發主管 Bob Martell。我們還將在通話結束時提供問答環節。

I'd like now to turn the call over to Jim.

我現在想把電話轉給吉姆。

Thank you, Diantha. Good morning, everyone, and welcome to Curis' Fourth Quarter Business Update Call.

謝謝你，黛安莎。大家早上好，歡迎來到 Curis 的第四季度業務更新電話會議。

This past quarter, we made important progress with our lead clinical candidate, emavusertib, which is currently being evaluated in 2 clinical studies. The TakeAim Leukemia study, a Phase I/II study with both monotherapy and combination arms for patients with relapsed or refractory acute myeloid leukemia or AML and high-risk myelodysplastic syndromes or MDS. And the TakeAim Lymphoma study, a Phase I/II combination study with ibrutinib for patients with relapsed or refractory NHL and other hematologic malignancies.

上個季度，我們的主要臨床候選藥物 emavusertib 取得了重要進展，目前正在兩項臨床研究中對其進行評估。 TakeAim 白血病研究是一項 I/II 期研究，針對複發或難治性急性髓性白血病或 AML 和高危骨髓增生異常綜合徵或 MDS 患者進行單藥治療和聯合治療。 TakeAim 淋巴瘤研究是一項 I/II 期聯合依魯替尼治療復發或難治性 NHL 和其他血液惡性腫瘤患者的研究。

We were especially pleased to present an update of clinical data from the TakeAim Leukemia study, in which AML patients with a FLT3 mutation had a CR rate of 29%. AML patients with a spliceosome mutation had a CR/CRh rate of 22% and MDS patients with a spliceosome mutation had an overall response rate of 45%, with all 5 responses achieving a marrow complete remission. This update doubled the size of our earlier data set and reaffirmed emavusertib's potential to be an important therapeutic alternative for patients with AML or MDS.

我們特別高興地介紹了 TakeAim 白血病研究的最新臨床數據，其中具有 FLT3 突變的 AML 患者的 CR 率為 29%。帶有剪接體突變的 AML 患者的 CR/CRh 率為 22%，帶有剪接體突變的 MDS 患者的總緩解率為 45%，所有 5 種緩解均達到骨髓完全緩解。這次更新使我們早期數據集的大小翻了一番，並重申了 emavusertib 有潛力成為 AML 或 MDS 患者的重要治療選擇。

We've also made important progress in our work to resolve the partial clinical hold on our leukemia study. In last quarter's call, we announced that the FDA had approved the reopening of our clinical sites so that we could enroll 9 additional patients at the 200-milligram dose level to facilitate discussions with FDA on the recommended Phase II dose or RP2D and the resolution of the partial clinical hold. We're pleased to announce today that we have completed the reopening of our sites, and have also completed the enrollment of the 9 additional patients requested by FDA. This is ahead of schedule, and we believe reflects the excitement surrounding this novel therapeutic and the critical unmet need in this sorely underserved patient population. We expect to collect data for these patients in Q2 and meet with FDA in Q3 to review those data.

我們在解決白血病研究的部分臨床問題方面也取得了重要進展。在上個季度的電話會議中，我們宣布 FDA 已批准重新開放我們的臨床站點，以便我們可以在 200 毫克劑量水平上招募 9 名額外患者，以促進與 FDA 就推薦的 II 期劑量或 RP2D 進行討論，並解決部分臨床持有。我們今天很高興地宣布，我們已經完成了站點的重新開放，並且還完成了 FDA 要求的另外 9 名患者的註冊。這比計劃提前了，我們相信這反映了圍繞這種新療法的興奮以及在這個服務嚴重不足的患者群體中未滿足的關鍵需求。我們希望在第二季度收集這些患者的數據，並在第三季度與 FDA 會面以審查這些數據。

We also continue to enroll in our TakeAim Lymphoma study in which we are focusing on primary CNS lymphoma and treating patients with the combination of emavusertib and ibrutinib. In short, we had a very productive end of 2022 and that momentum is carried forward into 2023. We look forward to working with the FDA in the months ahead to gain alignment on RP2D in our TakeAim Leukemia study and resolution of the partial clinical hold.

我們還繼續參加我們的 TakeAim 淋巴瘤研究，在該研究中我們專注於原發性 CNS 淋巴瘤，並使用 emavusertib 和 ibrutinib 聯合治療患者。簡而言之，我們在 2022 年結束時非常富有成效，這種勢頭將延續到 2023 年。我們期待在未來幾個月與 FDA 合作，在我們的 TakeAim 白血病研究中與 RP2D 取得一致，並解決部分臨床暫停。

With that, I'll turn the call back over to Diantha to review our financial results for the quarter. Diantha?

有了這個，我會把電話轉回 Diantha 來審查我們本季度的財務業績。石竹？

Thank you, Jim. For the fourth quarter of 2022, Curis reported a net loss of $11.3 million or $0.12 per share as compared to a net loss of $13.6 million or $0.15 per share for the same period in 2021. Curis reported a net loss of $56.7 million or $0.61 per share for the 12 months ended December 31, 2022, as compared to a net loss of $45.4 million or $0.50 per share for the same period in 2021.

謝謝你，吉姆。 2022 年第四季度，Curis 報告淨虧損 1130 萬美元或每股 0.12 美元，而 2021 年同期為淨虧損 1360 萬美元或每股 0.15 美元。Curis 報告淨虧損 5670 萬美元或每股 0.61 美元截至 2022 年 12 月 31 日止 12 個月的股價，而 2021 年同期為淨虧損 4540 萬美元或每股 0.50 美元。

Revenues for the fourth quarter of 2022 and 2021 were $2.9 million and $3.1 million, respectively. Revenues for the 12 months ended December 31, 2022, and December 31, 2021, were $10.2 million and $10.6 million, respectively. Operating expenses for the fourth quarter of 2022 were $13.1 million as compared to $15.7 million for the same period in 2021. Operating expenses for the 12 months ended December 31, 2022, were $63.2 million as compared to $52.7 million for the same period in 2021. And consisted of the following: royalty revenues, which comprised amounts due to third-party university patent licensors in connection with the Genentech and Roche's Erivedge net sales were $0.1 million for the fourth quarter of 2022 as compared to $0.2 million for the same period in 2021. Cost of royalty revenues for the 12 months ended December 31, 2022, were $0.3 million as compared to $0.5 million for the same period in 2021.

2022 年和 2021 年第四季度的收入分別為 290 萬美元和 310 萬美元。截至2022年12月31日和2021年12月31日止12個月的收入分別為1020萬美元和1060萬美元。 2022 年第四季度的運營費用為 1310 萬美元，而 2021 年同期為 1570 萬美元。截至 2022 年 12 月 31 日止 12 個月的運營費用為 6320 萬美元，而 2021 年同期為 5270 萬美元。包括以下內容：2022 年第四季度的特許權使用費收入為 10 萬美元，而 2021 年同期為 20 萬美元，其中包括與基因泰克和羅氏的 Erivedge 淨銷售額相關的第三方大學專利許可人應得的款項. 截至 2022 年 12 月 31 日止 12 個月的特許權使用費收入成本為 30 萬美元，而 2021 年同期為 50 萬美元。

Research and development expenses were $8.7 million for the fourth quarter of 2022 as compared to $10.8 million for the same period in 2021. The decrease in research and development expense for the quarter is primarily attributable to decreased personnel, manufacturing and clinical development costs. Research and development expenses were $43.3 million for the 12 months ended December 31, 2022, as compared to $34.9 million for the same period in '21.

2022 年第四季度的研發費用為 870 萬美元，而 2021 年同期為 1080 萬美元。本季度研發費用的減少主要是由於人員、製造和臨床開發成本的減少。截至 2022 年 12 月 31 日止的 12 個月，研發費用為 4330 萬美元，而 2021 年同期為 3490 萬美元。

General and administrative expenses were $4.3 million for the fourth quarter ended December 31, 2022, as compared to $4.8 million for the same period in 2021. The decrease in general and administrative expenses was driven primarily by a decrease in personnel costs. General and administrative expenses were $19.6 million for the 12 months ended December 31, 2022 as compared to $17.3 million for the same period in '21. For the fourth quarters of '22 and '21, total other expense was $1.1 million, respectively. Other expense was $3.7 million for the 12 months ended December 31, 2022, as compared to $3.4 million for the same period in 2021. Other expense net for the year ended December 31, 2022, primarily consisted of expense related to future royalty payments, partially offset by interest income.

截至 2022 年 12 月 31 日的第四季度，一般和行政費用為 430 萬美元，而 2021 年同期為 480 萬美元。一般和行政費用的減少主要是由於人事成本的減少。截至 2022 年 12 月 31 日止的 12 個月，一般和行政費用為 1,960 萬美元，而 2021 年同期為 1,730 萬美元。 22 年和 21 年第四季度，其他總費用分別為 110 萬美元。截至 2022 年 12 月 31 日止的 12 個月，其他費用為 370 萬美元，而 2021 年同期為 340 萬美元。截至 2022 年 12 月 31 日止年度的其他費用淨額，主要包括與未來特許權使用費相關的費用，部分抵消利息收入。

Other expense net for the year ended December 31, 2021, primarily consisted of imputed interest expense related to future royalty payments, partially offset by a gain recognized upon the forgiveness of a PPP loan.

截至 2021 年 12 月 31 日止年度的其他費用淨額，主要包括與未來特許權使用費相關的估算利息費用，部分被 PPP 貸款免除後確認的收益所抵消。

As of December 31, 2022, Curis' cash, cash equivalents and investments totaled $85.6 million, and there were approximately 96.6 million shares of common stock outstanding. We continue to have a strong cash position and expect our existing cash, cash equivalents and investments should enable us to maintain our planned operations into 2025.

截至2022年12月31日，Curis的現金、現金等價物和投資總額為8560萬美元，流通在外的普通股約為9660萬股。我們繼續擁有強勁的現金狀況，並預計我們現有的現金、現金等價物和投資將使我們能夠將計劃的運營維持到 2025 年。

With that, I'd like to open up the call for questions. Operator?

有了這個，我想打開問題的電話。操作員？

(Operator Instructions) And our first question will come from Ed White of H.C. Wainwright.

（操作員說明）我們的第一個問題將來自 H.C. 的 Ed White。溫賴特。

Jim, previously, you had said that TakeAim Lymphoma, you had expected data in 2023. Now that we're in 2023, can you give us a little bit of guidance as to when we should expect to see that data in this year?

吉姆，之前，你曾說過 TakeAim 淋巴瘤，你預計 2023 年會有數據。現在我們已經到了 2023 年，你能給我們一些指導，告訴我們今年應該什麼時候看到這些數據嗎？

Thanks, Ed. Yes, I think our expectation remains the same. We're hoping to provide an update by year-end. If things change between now and then, of course, we'll let you know. But we're very pleased with where we stand on both studies.

謝謝，埃德。是的，我認為我們的期望保持不變。我們希望在年底前提供更新。如果事情不時發生變化，當然，我們會通知您。但我們對我們在這兩項研究中的立場感到非常滿意。

Great. And you didn't mention the VISTA program at all. I know it's been halted. I just wanted to get your thoughts on -- is anything changing there? Is there any thoughts being given to restarting this program in 2023? Or is that perhaps more out there further?

偉大的。而且您根本沒有提到 VISTA 程序。我知道它已經停止了。我只是想听聽你的想法——那裡有什麼變化嗎？是否有關於在 2023 年重啟該計劃的想法？還是那可能更遠？

Well, yes, I think it's premature for us to think about restarting it just yet. Remember, the reason we paused it had nothing to do with our excitement about the program. It's a terrific target. It's a terrific program. We were making really nice progress I thought. I think it was more about given the financial climate, we needed to cut back our cash burn in order to ensure that cash went to 2025. And until we get to a point where we're confident that the market is different or that we've got the ability to access cash that doesn't put any compromising impact on to IRAK4. We need to go all in on IRAK4.

嗯，是的，我認為我們現在考慮重新啟動它還為時過早。請記住，我們暫停它的原因與我們對該程序的興奮無關。這是一個了不起的目標。這是一個了不起的程序。我認為我們取得了非常好的進展。我認為更多的是考慮到金融環境，我們需要減少現金消耗以確保現金到 2025 年。直到我們確信市場有所不同或者我們“我們能夠獲得不會對 IRAK4 產生任何不利影響的現金。我們需要全力投入 IRAK4。

So as I said, we're really excited for where we are right now. I think we're in a great position to add value to the IRAK4 program this year. And we'll be keeping our eye on the financial markets more broadly as we go through the course of 2023.

所以正如我所說，我們對我們現在所處的位置感到非常興奮。我認為我們今年處於為 IRAK4 計劃增加價值的有利位置。到 2023 年，我們將更廣泛地關注金融市場。

Okay. Since you brought up financials, maybe a question for Diantha, just regarding the -- your thoughts on R&D expense throughout the year as the development of (inaudible) gets back on track. How should we be thinking about the ramp or perhaps just not a ramp or flattening of the R&D expense.

好的。既然你提出了財務問題，也許是 Diantha 的一個問題，只是關於 - 隨著（聽不清）的發展重回正軌，你對全年研發費用的想法。我們應該如何考慮研發費用的上升，或者可能只是不上升或趨於平穩。

So Ed, if you recall, we announced our reprioritization in November. And I think Q4, as we said, the costs are coming down. So I think sort of where we sit in Q4 will likely sort of be the sort of ongoing run rate, although I will say it could come down a little bit further just by virtue of the fact we did not avail ourselves of the full quarter post reprioritization.

所以 Ed，如果你還記得的話，我們在 11 月宣布了重新確定優先級。正如我們所說，我認為第四季度的成本正在下降。因此，我認為我們在第四季度所處的位置可能是一種持續的運行率，儘管我會說它可能會進一步下降一點，因為我們沒有利用整個季度發布的事實重新排序。

The next question comes from Soumit Roy of JonesTrading.

下一個問題來自 JonesTrading 的 Soumit Roy。

Congrats on all the progress. The 9 patients, you mentioned, the additional new patients got enrolled. Are these all AML patients or they are AML and MDS if you can give us some idea. And also, do you think if you can provide any color on if they are very late line patients as you have seen prior to the whole enrollment hold today, you are getting more late-line patients?

祝賀所有的進步。你提到的 9 名患者，額外的新患者入組了。如果您能給我們一些想法，這些都是 AML 患者還是 AML 和 MDS。而且，你是否認為如果你能提供任何顏色，如果他們是非常晚排隊的患者，就像你在今天整個登記暫停之前看到的那樣，你會得到更多的晚排隊患者嗎？

Soumit. This is Bob Martell. Yes, we're currently really trying to address the FDA's question around the dosing in particular, at the lower dose of 200 milligrams. And so we've enrolled these 9 patients as part of the regular Phase I protocol, which is open to both AML and MDS. We noticed that patients -- many of the patients that we've enrolled on the study have had lots of prior lines of therapy. And that's obviously a challenging population to treat. So while we're not restricting per se, we always seek patients who perhaps a little bit earlier in their lines of therapy. But for these 9 patients, we haven't made specific guidelines.

蘇米特。這是鮑勃·馬爹利。是的，我們目前確實在嘗試解決 FDA 關於劑量的問題，特別是在 200 毫克的較低劑量下。因此，我們將這 9 名患者納入常規 I 期方案，該方案對 AML 和 MDS 均開放。我們注意到患者——我們在研究中登記的許多患者之前接受過很多治療。這顯然是一個難以治療的人群。因此，雖然我們本身並沒有限制，但我們總是尋找可能更早接受治療的患者。但是對於這9位患者，我們還沒有做出具體的指導方針。

Totally understandable. That's really helpful. And one last question is you previously had 4 patients on emavusertib and venetoclax combination with 50% response rate. Can you confirm if these patients are still being treated?

完全可以理解。這真的很有幫助。最後一個問題是您之前有 4 名患者接受了 emavusertib 和維奈托克聯合治療，緩解率為 50%。您能否確認這些患者是否仍在接受治療？

Yes. We haven't really given any updates on -- since the ASH presentation. We're not prepared on this call to provide any further detail other than the fact that the data that we saw was quite impressive where we had deep responses in the patient's AML, MDS, Three out of the 4 patients who had responses -- assessments available had pretty dramatic reductions in their blast counts. And as you mentioned, 2 of them with getting their blast count back to normal. So as you know, just to talk a little bit to the mechanism, venetoclax hits BCL2, well, the other major anti-apoptotic factor in these patients, that's preventing the cancer from undergoing apoptosis is MCL1. And in fact, hitting IRAK4 reduces MCL1. So we think this is a great potential combination from a mechanistic standpoint, and we're really excited, ultimately to get more data on that combination.

是的。自從 ASH 演示以來，我們還沒有真正提供任何更新。我們不准備在這次電話會議上提供任何進一步的細節，除了我們看到的數據非常令人印象深刻，我們對患者的 AML、MDS 有深入反應，4 名患者中有 3 名有反應——評估可用的爆炸計數顯著減少。正如您提到的，其中 2 人的爆炸計數恢復正常。因此，如您所知，只需談談機制，venetoclax 擊中 BCL2，好吧，這些患者的另一個主要抗細胞凋亡因子，即防止癌症發生細胞凋亡的是 MCL1。事實上，擊中 IRAK4 會降低 MCL1。所以我們認為從機械的角度來看這是一個很有潛力的組合，我們真的很興奮，最終能得到更多關於這種組合的數據。

The next question comes from Yale Jen of Laidlaw & Co.

下一個問題來自 Laidlaw & Co. 的 Yale Jen。

Just for the 9 patients you recently completed, are they have any sort of difference compared to the prior patients? Or they are very much similar to the ones you have enrolled before?

就您最近完成的9個患者而言，與之前的患者相比，他們有什麼不同嗎？或者它們與您之前註冊的非常相似？

Yes, Yale Jen. I would say there's basically similar for all intents and purposes to the prior patients under Phase I. In general, we're enrolling patients, essentially last line patients who've had all available therapies. And so again, these patients are in a very difficult situation. And like we've said before, the fact that we've been seeing efficacy, such striking efficacy in the earlier patients is pretty amazing, honestly. So we're just continuing to enroll that same population. Eventually, once we identify a recommended Phase II dose, we'll be, as we've mentioned, selecting targeted patients who are much more likely to respond. So patients with the 2 splicing factor mutations, SF3B1 and U2AF1 will be selecting only those patients going forward once we get to our recommended dose.

是的，耶魯仁。我想說的是，所有意圖和目的與第一階段的先前患者基本相似。總的來說，我們正在招募患者，基本上是接受過所有可用療法的最後一線患者。因此，這些患者再次處於非常困難的境地。就像我們之前說過的，老實說，我們已經看到了療效，在早期患者中如此顯著的療效是非常驚人的。所以我們只是繼續招收同樣的人群。最終，一旦我們確定了推薦的 II 期劑量，正如我們所提到的，我們將選擇更有可能產生反應的目標患者。因此，一旦我們達到推薦劑量，具有 2 個剪接因子突變 SF3B1 和 U2AF1 的患者將僅選擇那些繼續前進的患者。

Similarly, the FLT3 mutation as well, that's another selected patient population that we'll be investigating in the future as soon as we get our recommended dose.

同樣，FLT3 突變也是如此，這是我們在獲得推薦劑量後將在未來調查的另一個選定患者群體。

Okay. Great. And maybe just to elaborate a little bit more in terms of the previous question, which is what you -- what should we see any read-through from the ASH meetings, the data is presented not too long ago.

好的。偉大的。或許只是就上一個問題進行更多闡述，這就是你——我們應該從 ASH 會議的任何通讀中看到什麼，數據是不久前提供的。

Well, I think the biggest read-through from my perspective was the fact that, as you remember, back in 2022, we had, had pretty striking data early in the year and towards the ASH of the year prior. One of the exciting things about ASH this last year was that we essentially doubled the patient population and continue to see very dramatic activity, including multiple new responses. Oftentimes, you can get a signal in the first couple of patients and then it never pans out in the end.

好吧，我認為從我的角度來看，最大的通讀是這樣一個事實，正如你記得的那樣，早在 2022 年，我們在年初和前一年的 ASH 就有了非常驚人的數據。去年關於 ASH 的一件令人興奮的事情是，我們的患者人數基本上翻了一番，並繼續看到非常引人注目的活動，包括多種新的反應。通常，您可以在前幾名患者身上得到信號，但最終卻沒有成功。

Well, in this case, it's continuing as we expand our database. And also the fact that these patients are having really durable responses when they get a response over 6 months. And almost all of the patients had, had prior HMA, which is, as you know, a very difficult patient population to treat. The median survival, as we've said before, in AML for these patients is about 2.5 months. So we've been really excited to see the data that we've gotten so far. And that was really the big read-through is that we continue to get it as, we're like essentially doubling the patient population.

好吧，在這種情況下，它會隨著我們擴展數據庫而繼續。還有一個事實是，這些患者在 6 個月以上得到緩解時，會產生真正持久的緩解。幾乎所有患者都曾有過 HMA，如您所知，這是一個非常難以治療的患者群體。正如我們之前所說，這些患者的 AML 中位生存期約為 2.5 個月。因此，我們很高興看到迄今為止獲得的數據。這真的是一個很大的通讀，我們繼續得到它，因為我們基本上將患者人數翻了一番。

[Operator Instructions] And our next question will come from Li Watsek of Cantor Fitzgerald.

[操作員說明] 我們的下一個問題將來自 Cantor Fitzgerald 的 Li Watsek。

This is Rosemary on for Li. So regarding the 9 patients and your discussion with the FDA, would you be able to tell us potentially what types of data you would be collecting and talking about with them. And when do you anticipate you might communicate the feedback with the Street after the 3Q meeting?

這是李的迷迭香。因此，關於這 9 名患者以及您與 FDA 的討論，您能否告訴我們您將收集哪些類型的數據並與他們討論？您預計什麼時候可以在第三季度會議後與華爾街溝通反饋？

Well, let me start with the data and then maybe Jim can talk about the communication. So the FDA is -- so you may be familiar with Project Optimus. So let me start from there. This is an effort that the FDA has undertaken in the last year or so to try to participate much more in the determination of the recommended Phase II dose for essentially all oncology drugs that are going through Phase I. And so they've kind of set some guidelines around this, and one of which is exploring multiple doses where there is some efficacy and safety. So in the example of emavusertib, we've had actually 3 doses that met our safety criteria, meaning that we felt that they were safe.

好吧，讓我從數據開始，然後也許吉姆可以談談溝通。所以 FDA 是——所以你可能熟悉 Project Optimus。所以讓我從那裡開始。這是 FDA 在過去一年左右所做的努力，試圖更多地參與確定幾乎所有正在進行 I 期的腫瘤藥物的 II 期推薦劑量。因此他們有點設定一些關於此的指導方針，其中之一是探索具有一定療效和安全性的多劑量。所以在 emavusertib 的例子中，我們實際上有 3 劑符合我們的安全標準，這意味著我們認為它們是安全的。

They didn't have a high rate of dose-limiting toxicities but all 3 doses also had some efficacy. We had explored the 300 and the 400 dose twice daily and felt that the 300 offer comparable efficacy to the 400 when we evaluated that. Well, we had originally only evaluated 3 patients at the 200. So the FDA just wanted to explore that a little bit more, and that's the goal for the 9 patients is to get that total up to 12 patients. So that since we did have some efficacy at that dose level, they wanted to better understand that as well. And ultimately, that's the driving force around why they've asked us for this. And we don't think this is unique to Curis or emavusertib, I think that they're really doing this for all companies who are in their early Phase I development.

它們的劑量限制性毒性發生率不高，但所有 3 種劑量都有一定療效。我們每天兩次探索 300 和 400 劑量，在我們評估時認為 300 提供與 400 相當的療效。好吧，我們最初只評估了 200 名患者中的 3 名患者。因此 FDA 只是想對此進行更多探索，這就是 9 名患者的目標是使患者總數達到 12 名。因此，既然我們在那個劑量水平上確實有一些療效，他們也想更好地理解這一點。最終，這就是他們為什麼要我們這樣做的驅動力。我們不認為這是 Curis 或 emavusertib 獨有的，我認為他們確實在為所有處於早期 I 期開發的公司這樣做。

Yes. Let me add to that, Li. So first, when we talk about the different dose levels, as Bob said, we know Project Optimus is about trying to find the lowest dose that can lead to that optimal efficacy level. I think one of the things that gets us so excited is that all of the doses at 200, 300 and 400 that we tested have efficacy. That's the good news. It's also the good news if you're interested in Project Optimus because, of course, it means you want to make sure you fully explore those. The question about data that we would have by the end of the year, we're still anticipating that we're going to have data in both leukemia and lymphoma by the end of the year.

是的。讓我補充一點，李。所以首先，當我們談論不同的劑量水平時，正如 Bob 所說，我們知道 Project Optimus 是關於試圖找到可以導致最佳療效水平的最低劑量。我認為讓我們如此興奮的一件事是我們測試的所有 200、300 和 400 劑量都有效。這是個好消息。如果您對擎天柱計劃感興趣，這也是個好消息，因為當然，這意味著您要確保充分探索這些內容。關於到年底我們將獲得的數據的問題，我們仍然預計到今年年底我們將獲得白血病和淋巴瘤的數據。

My hope is that we're going to have some output from FDA as well to talk about. Whether or not we end up at 200 or 300 remains to be seen, of course. Right now, we're just doing everything that the FDA has asked, and we are thrilled that we were able to get the sites open and patients enrolled ahead of schedule. And I think, as I said in my comments, it reflects both the dire situation that these patients are in, the critical unmet need and the excitement among our investigators to get this new therapy in treating patients.

我希望我們也能從 FDA 獲得一些成果來討論。當然，我們最終會達到 200 還是 300 還有待觀察。現在，我們只是在做 FDA 要求的一切，我們很高興我們能夠提前開放站點並讓患者入組。我認為，正如我在評論中所說，這既反映了這些患者所處的可怕情況、未滿足的關鍵需求，也反映了我們的研究人員對採用這種新療法治療患者的興奮。

And Li, and just to give a little bit more detail on the specific data, one thing that the FDA really likes is what they call an efficacy response analysis. And so -- I'm sorry, exposure response analysis. So what they look at closely is the actual exposure of emavusertib in each patient. So as you know, we're doing detailed pharmacokinetic analyses on all of these patients -- so they'll look at that. They'll compare that to safety. They'll compare it to efficacy and that will help give them and us a very granular understanding of the optimal dose. And so that's really the fundamental aspect of what we're going to be looking for.

而李，只是為了提供更多關於具體數據的細節，FDA 真正喜歡的一件事是他們所謂的療效反應分析。所以 - 對不起，曝光反應分析。因此，他們仔細觀察的是每位患者 emavusertib 的實際暴露情況。因此，如您所知，我們正在對所有這些患者進行詳細的藥代動力學分析——所以他們會對此進行研究。他們會將其與安全進行比較。他們會將其與功效進行比較，這將有助於讓他們和我們對最佳劑量有一個非常細緻的了解。因此，這確實是我們要尋找的基本方面。

Got it. And sorry, maybe just one quick follow-up. If you potentially have your hold lifted in 3Q or 4Q, how quickly do you think you could restart?

知道了。抱歉，也許只是一個快速跟進。如果您可能在 3 季度或 4 季度取消持有，您認為您可以多快重啟？

Well, we're already -- the studies are actually already open and going. So it would essentially be -- once we have that agreement, the studies are already open, and we continue with that dose level. So I don't anticipate any significant delay once that happens.

好吧，我們已經——研究實際上已經開始並正在進行。所以它基本上是——一旦我們達成協議，研究就已經開始，我們將繼續使用那個劑量水平。因此，我預計一旦發生這種情況不會有任何重大延遲。

Yes, Rosemary, let me add to that. So that was when I said it kind of quickly in the comments, but -- of course, when we went on hold, you have to effectively shut your sites down. The big change that we had at the end of last year was they allowed us to resume enrollment. So we went through the process already in Q4 of getting all our sites open and then recruiting new patients. So to Bob's point, as far as the FDA is concerned, we are open. We needed to recruit those 9 patients, but that's not done. And we're now in the process of wait for the data, give it to the FDA and see which dose they prefer. Do they prefer 200 or 300? Either way, our sites are open and we're off to the races.

是的，羅斯瑪麗，讓我補充一下。所以那時我在評論中說得很快，但是 - 當然，當我們擱置時，你必須有效地關閉你的網站。我們在去年年底發生的重大變化是他們允許我們恢復招生。因此，我們已經在第四季度完成了開放所有站點然後招募新患者的過程。所以就鮑勃的觀點而言，就 FDA 而言，我們是開放的。我們需要招募這 9 名患者，但尚未完成。我們現在正在等待數據，將其提供給 FDA，看看他們更喜歡哪種劑量。他們更喜歡 200 還是 300？無論哪種方式，我們的網站都是開放的，我們要開始比賽了。

As soon as you get the dose, you can go?

一旦你得到劑量，你就可以走了？

We can continue enrollment at that dose, which ultimately, we feel like we can accumulate data there. We're interested in let's step back and think about our overall potential registrational plan. So we've mentioned that there's a couple of opportunities for very rapid registration and that would be single-arm studies in FLT3 mutated -- patients with FLT3 mutated AML; and secondly, in patients with splicing factor mutated AML. And so those are single-arm studies. As soon as we have our dose, we can start expanding that. And really at that point, having much greater clarity on what our registrational plan will be.

我們可以繼續以該劑量註冊，最終，我們覺得我們可以在那裡積累數據。我們有興趣讓我們退後一步，考慮一下我們的整體潛在註冊計劃。所以我們已經提到，有幾個非常快速註冊的機會，那就是對 FLT3 突變的單臂研究——患有 FLT3 突變的 AML 患者；其次，在剪接因子突變的 AML 患者中。所以這些都是單臂研究。一旦我們有了劑量，我們就可以開始擴大它。真的在那個時候，我們的註冊計劃將更加清晰。

This concludes our question-and-answer session. I would like to turn the conference back over to the company's President and Chief Executive Officer, James Dentzer, for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給公司總裁兼首席執行官 James Dentzer，聽取任何閉幕詞。

Thank you, operator, and thank you, everyone, for joining today's call. And as always, thank you to the patients and the families participating in our clinical trials; to our team at Curis for their hard work and commitment; and to our partners at Aurigene, ImmuNext and The NCI for their ongoing help and support. We look forward to updating you again soon. Operator?

謝謝接線員，也謝謝大家參加今天的電話會議。一如既往，感謝參與我們臨床試驗的患者和家屬；感謝我們在 Curis 的團隊，感謝他們的辛勤工作和承諾；以及我們在 Aurigene、ImmuNext 和 NCI 的合作夥伴，感謝他們一直以來的幫助和支持。我們期待很快再次為您更新。操作員？

The conference has now concluded. Thank you again for your participation, and you may now disconnect.

會議現已結束。再次感謝您的參與，您現在可以斷開連接。