Curis Inc (CRIS) 2023 Q4 法說會逐字稿

Morning, and welcome to Curis' fourth-quarter 2023 business update call. (Operator Instructions) After the company's prepared remarks call participants will have an opportunity to ask questions. (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，歡迎參加 Curis 2023 年第四季業務更新電話會議。（操作員說明）在公司準備好講話後，電話參與者將有機會提問。（操作員說明）請注意此事件正在被記錄。我現在想將會議交給 Curis 財務長 Diantha Duvall。黛安莎，請繼續。

Thank you, and welcome to Curis' fourth-quarter 2023 business update call. Before we begin, I would like to encourage everyone to go to our Investor section of our website at www.curis.com to find our fourth-quarter 2023 business update release and related financial tables. 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.

謝謝，歡迎參加 Curis 2023 年第四季業務更新電話會議。在開始之前，我想鼓勵大家造訪我們網站 www.curis.com 的投資者部分，尋找我們的 2023 年第四季業務更新版本和相關財務表格。我還想提醒大家，在電話會議期間，我們將根據我們當前的期望和信念做出前瞻性聲明。這些陳述存在一定的風險和不確定性，實際結果可能有重大差異。有關更多詳細信息，請參閱我們向 SEC 提交的文件。

Joining me on today's call are Jim Dentzer, President and Chief Executive Officer; and Jonathan Zung, Chief Development Officer. We will also be available for a question-and-answer period at the end of our call. I'd now like to turn the call over to Jim. Jim?

與我一起參加今天電話會議的還有總裁兼執行長 Jim Dentzer；和首席開發長 J​​onathan Zung。我們也會在通話結束時進行問答環節。我現在想把電話轉給吉姆。吉姆？

Thank you, Diantha. Good morning, everyone, and welcome to Curis' fourth-quarter business update call. I'd like to start today's call with a look back over the past 12 months. Entering 2023, the whole biotech industry was struggling in the headwinds of a growing financial market. Curis faced all of that and the daunting challenge of seeing our Leukemia study stalled on partial clinical hold with the FDA. In the face of that adversity, the Curis team rose to the challenge. We worked tirelessly in answering questions posed by the FDA. This included enrolling additional patients at 200 milligrams BID and performing additional analysis. As a result, we were able to confirm the safety profile of emavusertib gain alignment on the optimal dosing regimen for monotherapy and secure the removal of the partial clinical hold, a full quarter earlier than expected.

謝謝你，黛安莎。大家早上好，歡迎參加 Curis 第四季業務更新電話會議。我想在今天的電話會議開始時回顧一下過去 12 個月的情況。進入2023年，整個生技產業在不斷成長的金融市場的逆風中苦苦掙扎。Curis 面臨著所有這些，以及看到我們的白血病研究因 FDA 的部分臨床擱置而陷入停滯的艱鉅挑戰。面對逆境，庫里斯團隊迎難而上。我們孜孜不倦地回答 FDA 提出的問題。這包括以 200 毫克 BID 招募更多患者並進行額外分析。因此，我們能夠確認 emavusertib 的安全性與單一療法的最佳劑量方案一致，並確保取消部分臨床保留，比預期提前了整整一個季​​度。

We then redirected our energy to reopening clinical sites and enrolling new patients. In our monotherapy study, we are targeting a genetically-defined population of relapsed refractory AML patients with a FLT3 or spliceosome mutation. Enrollment is going quite well and we expect to have a data update by midyear. While that study advances, we have initiated a front-line study of emavusertib in combination with azacitidine and venetoclax for all AML patients regardless of their mutation status. This study is being conducted at sites in Spain, Germany and Italy, and we expect preliminary data from this study in the second half of this year. All in all, a terrific year of progress in leukemia.

然後，我們將精力轉向重新開放臨床中心並招募新患者。在我們的單一療法研究中，我們的目標是具有 FLT3 或剪接體突變的遺傳定義的複發難治性 AML 患者群體。報名進展順利，我們預計在年中之前更新數據。在該研究取得進展的同時，我們已經針對所有 AML 患者啟動了一項 emavusertib 聯合阿扎胞苷和維奈托克的一線研究，無論其突變狀態如何。這項研究正在西班牙、德國和義大利進行，我們預計今年下半年將獲得這項研究的初步數據。總而言之，這是白血病治療取得巨大進展的一年。

Now let's turn to our lymphoma program, which is generating an equally high level of interest. After reviewing initial data collected across multiple NHL subtypes, we focused our efforts on the ultra-orphan indication of primary CNS lymphoma or PCNSL, where we are evaluating emavusertib in combination with ibrutinib. We identified key sites, initiated enrollment.

現在讓我們談談我們的淋巴瘤項目，該項目引起了同樣高的興趣。在審查了多種 NHL 亞型收集的初始數據後，我們將工作重點放在原發性 CNS 淋巴瘤或 PCNSL 的超孤兒適應症上，我們正​​在評估 emavusertib 與 ibrutinib 的聯合治療。我們確定了關鍵地點，啟動了註冊。

And in December, we released new clinical data in relapsed refractory PCNSL at the ASH conference in San Diego. The meetings we had with physicians at ASH were terrific, and we were especially pleased to have Dr. Greg Nowakowski and Dr. Han Tun from the Mayo Clinic present the data. As a reminder, frontline treatment in PCNSL is high-dose methotrexate and chemo. When that no longer works, there is no approved second-line treatment. In our study, three of five patients were able to achieve complete remission of their disease.

12 月，我們在聖地牙哥舉行的 ASH 會議上發布了復發難治性 PCNSL 的新臨床數據。我們與 ASH 醫生舉行的會議非常精彩，我們特別高興梅奧診所的 Greg Nowakowski 博士和 Han Tun 博士介紹了這些數據。提醒一下，PCNSL 的第一線治療是大劑量甲胺蝶呤和化療。當這種方法不再有效時，就沒有經過批准的二線治療。在我們的研究中，五名患者中的三名能夠實現疾病的完全緩解。

It is admittedly a small number of patients. However, the response and interest from the clinical community was very encouraging. In the eight weeks since ASH our team has been fielding calls from clinical sites across the US and Europe wanting to participate in our trials. In fact, by the end of Q1, we expect to have doubled the number of clinical sites versus where we were a year ago.

誠然，這只是少數患者。然而，臨床界的反應和興趣卻非常令人鼓舞。自 ASH 召開以來的八週內，我們的團隊一直在接到來自美國和歐洲臨床中心的電話，希望參與我們的試驗。事實上，到第一季末，我們預計臨床站點數量將比一年前增加一倍。

Obviously, this is a reflection of the excitement about emavusertib, but it is also a reflection of the indefatigable efforts of the Curis team. I couldn't be more proud of them. Finally, in December, we announced that we entered into an agreement for an investigator-initiated trial to study the combination of emavusertib and pembrolizumab in patients with metastatic melanoma.

顯然，這是對emavusertib興奮的體現，但同時也是Curis團隊不懈努力的體現。我為他們感到無比驕傲。最後，在 12 月，我們宣布簽署了一項由研究者發起的試驗協議，以研究 emavusertib 和 pembrolizumab 聯合治療轉移性黑色素瘤患者。

We're excited that this study presents an opportunity to expand upon the research done in academic centers and the NCI to explore the potential of emavusertib in solid tumors. In short, we had an incredibly productive 2023, and we look forward to continuing that momentum in 2024.

我們很高興這項研究提供了一個機會，可以擴展學術中心和 NCI 所做的研究，以探索 emavusertib 在實體瘤中的潛力。簡而言之，我們在 2023 年取得了令人難以置信的成果，我們期待在 2024 年繼續保持這一勢頭。

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

接下來，我會將電話轉回給 Diantha，以審查我們本季的財務表現。黛安莎？

Thank you, Jim. For the fourth quarter of 2023 Curis reported a net loss of $11.7 million or $2.03 per share as compared to a net loss of $11.3 million or $2.35 per share for the same period in 2022. Curis reported a net loss of $47.4 million or $8.96 per share for the 12 months ended December 31, 2023, as compared to a net loss of $56.7 million or $12.14 per share for the same period in 2022.

謝謝你，吉姆。Curis 報告 2023 年第四季淨虧損 1,170 萬美元，即每股 2.03 美元，而 2022 年同期淨虧損為 1,130 萬美元，即每股 2.35 美元。Curis 報告稱，截至 2023 年 12 月 31 日的 12 個月淨虧損為 4,740 萬美元，即每股 8.96 美元，而 2022 年同期淨虧損為 5,670 萬美元，即每股 12.14 美元。

Revenues net for the fourth quarter of 2023 were $2.7 million compared to $2.9 million for the same period in 2022. Revenues net for the 12 months ended December 31, 2023, were $10 million compared to $10.2 million in 2022. Research and development expenses were $10 million for the fourth quarter of 2023 compared to $8.7 million in 2022. The increase in R&D was driven by higher clinical development costs. R&D was $39.5 million for the 12 months ended December 31, 2023, compared to $43 million in 2022.

2023 年第四季的淨收入為 270 萬美元，而 2022 年同期為 290 萬美元。截至 2023 年 12 月 31 日的 12 個月淨收入為 1,000 萬美元，而 2022 年為 1,020 萬美元。2023 年第四季的研發費用為 1,000 萬美元，而 2022 年第四季的研發費用為 870 萬美元。研發的增加是由較高的臨床開發成本所推動的。截至 2023 年 12 月 31 日的 12 個月，研發費用為 3,950 萬美元，而 2022 年為 4,300 萬美元。

General and administrative expenses were $4.9 million for the fourth quarter of 2023 compared to $4.3 million in 2022. The increase in G&A was driven primarily by higher professional legal and consulting services. G&A was $18.6 million for the 12 months ended December 31, 2023, compared to $19.6 million in 2022. Other income net was $0.5 million for the fourth quarter of 2023 compared to other expense net of $1.1 million in 2022. Other income net was $0.9 million for the 12 months ended December 31, 2023, compared to other expense net of $3.7 million in 2022.

2023 年第四季的一般及管理費用為 490 萬美元，而 2022 年第四季為 430 萬美元。一般行政費用的成長主要是由更專業的法律和諮詢服務所推動的。截至 2023 年 12 月 31 日的 12 個月，一般管理費用為 1,860 萬美元，而 2022 年為 1,960 萬美元。2023 年第四季的其他收入淨額為 50 萬美元，而 2022 年第四季的其他支出淨額為 110 萬美元。截至 2023 年 12 月 31 日的 12 個月，其他收入淨額為 90 萬美元，而 2022 年其他支出淨額為 370 萬美元。

Other income expense net consists of interest income and non-cash expense related to the sale of future royalties. As of December 31, 2023, Curis' cash, cash equivalents and investments totaled $56.3 million, and there were approximately 5.9 million shares of common stock outstanding. We continue to be in a solid cash position and expect that our existing cash, cash equivalents and investments will enable our planned operations into 2025. With that I'd like to open the call for questions. Operator?

其他收入支出淨額包括利息收入和與出售未來特許權使用費相關的非現金支出。截至2023年12月31日，Curis的現金、現金等價物及投資總額為5,630萬美元，已發行普通股約590萬股。我們繼續保持穩健的現金狀況，並預期我們現有的現金、現金等價物和投資將使我們的計畫營運持續到 2025 年。我想開始提問。操作員？

We will now begin the question-and-answer session. (Operator Instructions) Ed White, H.C. Wainwright.

我們現在開始問答環節。（操作員說明）Ed White, H.C.溫賴特。

Good morning. Thanks for taking my questions. Jim, you mentioned that in the primary CNS lymphoma trial, you have doubled the clinical sites open versus flat this time last year. I'm just wondering if you can let us know how many sites that is and how many sites you plan to open?

早安.感謝您回答我的問題。吉姆，您提到在原發性中樞神經系統淋巴瘤試驗中，去年這個時候，您將開放的臨床部位比平舖的臨床部位增加了一倍。我只是想知道您是否可以讓我們知道有多少網站以及您計劃開設多少網站？

Yeah. We try to get out of the details of the of the number of sites that we have in any given time, because, of course, we're always increasing them. But I think the reason why we mentioned that this call is because it's a reflection of the conference we had. Obviously, we were very encouraged by the data ourselves. And if you were at ASH, you saw that our booth was incredibly busy, but that's been followed up by being able to get these new sites up and running and online. And we've got, as I said, not the expectation to double by the end of Q1, but enthusiasm more broadly across the world, not just in the US. So it's really exciting from our perspective, and I'm hopeful that we can keep that momentum going forward.

是的。我們試圖擺脫在任何給定時間內我們擁有的站點數量的詳細信息，因為當然，我們總是在增加它們。但我認為我們之所以提到這次電話會議是因為它反映了我們所召開的會議。顯然，我們自己對這些數據感到非常鼓舞。如果您在 ASH，您會看到我們的攤位非常繁忙，但隨後我們能夠讓這些新網站上線並運行。正如我所說，我們並沒有期望在第一季末實現翻倍，而是全世界範圍內更廣泛的熱情，而不僅僅是在美國。因此，從我們的角度來看，這確實令人興奮，我希望我們能夠繼續保持這種勢頭。

Thanks. Could you give us your thoughts on the size of that primary CNS lymphoma market?

謝謝。您能否告訴我們您對原發性中樞神經系統淋巴瘤市場規模的看法？

Sure. It's an ultra-orphan market. It's one of the reasons why we selected it. So if you think across the landscape of non-Hodgkin's lymphoma and everywhere, where BTK gets used, of course, we have been targeting broadly. Anytime you use BTK, you're down regulating NF-kappa B from one pathway. There are a lot of BTK inhibitors targeting that path. We're the only one that targets the other path.

當然。這是一個超級孤兒市場。這也是我們選擇它的原因之一。因此，如果您考慮非何杰金氏淋巴瘤以及使用 BTK 的所有地方，當然，我們的目標範圍很廣。每當您使用 BTK 時，您都會從一條途徑下調 NF-kappa B。有許多 BTK 抑制劑針對該途徑。我們是唯一一個瞄準另一條路的人。

When we look across the landscape of non-Hodgkin's lymphoma, we've focused in on primary CNS first because it's so small incidence of 5 per million. That yields a lot of very attractive benefits from a development perspective, and especially in conversations with regulatory authorities. But also within primary CNS lymphoma, it's a fairly aggressive lymphoma where we believe we can address the disease quickly.

當我們審視非何杰金氏淋巴瘤的情況時，我們首先關注原發性中樞神經系統疾病，因為它的發生率非常低，只有百萬分之五。從發展的角度來看，這會產生許多非常有吸引力的好處，特別是在與監管機構的對話中。但在原發性中樞神經系統淋巴瘤中，它是一種相當侵襲性的淋巴瘤，我們相信我們可以快速解決這種疾病。

As you saw in the data, the three or five complete responses, we got a few of that in the first three months of treatment. So that's very helpful. And of course, there are no effective treatments. There are no approved drugs for relapsed-refractory PCNSL. So if we can go after a disease that is ultra-orphan, where there are no approved treatments, and we can see this kind of response from the drug, it's really encouraging.

正如您在數據中看到的，三到五個完整的反應，我們在治療的前三個月得到了其中的一些。這非常有幫助。當然，沒有有效的治療方法。目前還沒有批准用於治療復發難治性 PCNSL 的藥物。因此，如果我們能夠研究一種沒有經過批准的治療方法的超級孤兒疾病，並且我們可以看到藥物的這種反應，這真的很令人鼓舞。

Yes, thanks, Jim. And now perhaps if I could just ask it a big picture question. I wanted to get your thoughts on the potential in solid tumors. You had mentioned the IST beginning with the combination with Keytruda in metastatic melanoma. I just wanted to get your thoughts on that market in large in solid tumors overall.

是的，謝謝，吉姆。現在也許我可以問它一個大問題。我想了解您對實體瘤潛力的看法。您曾提到 IST 與 Keytruda 合併治療轉移性黑色素瘤。我只是想了解您對整個實體瘤市場的看法。

Yeah. So solid tumors is really exciting. We have been, of course, from the very beginning in identifying this target one of the things that was so exciting was that the role of IRAK4 in oncology more broadly was something that Curis had discovered and no one else knew about. So when we were designing the molecule originally, we had the Pharmacyclics template in mind, how do you go after a blockbuster indication or an indication with multi-billion-dollar revenue potential when no one else knows about it yet, and we designed that molecule. So that it would be effective in lymphoma, but also would confer some competitive advantage in leukemia and in solid tumors.

是的。所以實體瘤確實令人興奮。當然，從一開始我們就確定了這個靶點，其中一件令人興奮的事情是，IRAK4 在腫瘤學中更廣泛的作用是 Curis 發現的，而其他人不知道。因此，當我們最初設計該分子時，我們考慮了藥環學模板，當其他人還不知道它時，如何追求重磅炸彈適應症或具有數十億美元收入潛力的適應症，我們設計了該分子。因此它不僅對淋巴瘤有效，而且在白血病和實體瘤方面也具有一定的競爭優勢。

And as you know, our first studies started in lymphoma and that's, of course, where our most recent data are as well and that's really compelling. The data in lymphoma in the targeted population that we would expect to hit in the IRAK4 or spliceosome population and the FLT3 population, those data look really compelling. We've just started the front-line study. And then to your point in melanoma, this is the first time we've gone into solid tumors now there's been a lot of work done by the NCI and by academic centers in the studying emavusertib in various types of solid tumors.

如您所知，我們的第一項研究始於淋巴瘤，當然，我們最新的數據也是如此，這確實令人信服。我們預計在 IRAK4 或剪接體群體和 FLT3 群體中發生的目標群體中淋巴瘤的數據，這些數據看起來非常引人注目。我們剛開始一線研究。然後，關於黑色素瘤，這是我們第一次進入實體瘤領域，現在 NCI 和學術中心正在研究 emavusertib 在各種類型實體瘤中所做的大量工作。

So we know there's a lot of interesting work going on for example, in bladder cancer, in gastroesophageal cancer, in ovarian, in lung, in pancreatic. There are a number of different solid tumors where it looks like IRAK4 plays a significant role and where our drug might be able to confer benefit. This is the first time we're going into that. I think it's a little premature to talk about how large all of those markets are. But the idea is that we have a drug that looks as though it could provide incremental benefit that no other drug does in these very targeted markets individually. And of course, at a high level across the world of human solid tumors is really quite exciting.

所以我們知道有很多有趣的工作正在進行，例如在膀胱癌、胃食道癌、卵巢癌、肺癌、胰臟癌方面。IRAK4 在許多不同的實體腫瘤中發揮重要作用，而我們的藥物可能能夠帶來益處。這是我們第一次討論這個問題。我認為現在談論所有這些市場有多大還為時過早。但我們的想法是，我們有一種藥物看起來可以在這些非常有針對性的市場中提供其他藥物無法提供的增量益處。當然，人類實體瘤在世界範圍內的高水平確實非常令人興奮。

Thanks Jim. And last question, if I could. I just wanted to get your thoughts on partnering the product in solid tumors. Is that something that you'd be looking at or is this something as you expand into solid tumors that you think you could fund on your own going down the road?

謝謝吉姆。最後一個問題，如果可以的話。我只是想了解您對該產品在實體瘤中的應用的想法。這是您會關注的事情，還是當您擴展到實體瘤時您認為可以自己資助的事情？

Sure. So I mean, take the melanoma study as the case in point. Obviously, that's a study we would rather not pay for. There are a lot of trials may be 1,000. There are a lot of clinical trials going on right now of a company's drug in combination with pembro, Merck's PD-1, which is most people consider it deleting PD-1. But the way most of those work is, they beg Merck to give them free drug and then they run the study. We have the opposite. We're going to get data from this study and we are the one providing free drug. Merck's the one picking up the tab for the study.

當然。所以我的意思是，以黑色素瘤研究為例。顯然，這是一項我們寧願不花錢的研究。有很多試驗可能有1000次。現在正在進行許多臨床試驗，有一家公司的藥物與pembro聯合使用，默克公司的PD-1，大多數人認為它刪除了PD-1。但大多數工作的方式是，他們請求默克公司為他們提供免費藥物，然後他們進行研究。我們有相反的情況。我們將從這項研究中獲取數據，並且我們是提供免費藥物的人。默克公司為這項研究買單。

Obviously, what most companies would hope for is just getting free drug. Ideally, if we're going to expand the number of clinical studies that we can run, whether it's in lymphoma or in leukemia or now in solid tumors. At the minimum, we'd like to get 50-50 study. I think it's overly optimistic that we're going to be able to find all of our future studies are 100% funded by the partner without giving up any rights. But at this point in time, obviously, we're really excited that we're going to have the opportunity to get data across lymphoma, leukemia and now solid tumors. And we can afford to do it. So as long as we can afford to keep our rights and generate the data that show that this drug has such significant potential, I think that's our plan.

顯然，大多數公司所希望的只是獲得免費藥品。理想情況下，如果我們要擴大我們可以進行的臨床研究的數量，無論是淋巴瘤、白血病還是現在的實體瘤。至少，我們希望進行 50-50 次研究。我認為我們未來所有的研究都是 100% 由合作夥伴資助而不放棄任何權利，這太樂觀了。但顯然，此時此刻，我們真的很興奮，因為我們將有機會獲得淋巴瘤、白血病和實體瘤的數據。我們有能力做到這一點。因此，只要我們有能力保留我們的權利並產生表明這種藥物具有巨大潛力的數據，我認為這就是我們的計劃。

Okay, great. Thanks for taking my questions.

好的，太好了。感謝您回答我的問題。

You bet.

你打賭。

Soumit Roy, JonesTrading.

蘇米特·羅伊，瓊斯交易公司。

Good morning, everyone, and congratulations on all the progress on multiple fronts. One question on the frontline, the triple combo with emavusertib, HMA and venetoclax. We are starting -- you mentioned three different countries including Europe. Are you planning on initiating some US trial sites also? The second was --.

大家早安，恭喜在多個方面取得的所有進展。前線的一個問題是emavusertib、HMA 和venetoclax 的三重組合。我們正在開始——您提到了包括歐洲在內的三個不同國家。您是否也計劃在美國啟動一些試驗站點？第二個是--.

Go ahead.

前進。

Keeping this trial, is that in combination of ibrutinib, or still you are planning to do monotherapy emavusertib patients?

繼續這個試驗，是合併依魯替尼，還是仍計劃對emavusertib單藥治療的患者進行治療？

Okay.

好的。

So the first one first. So the initial study for the triplet, we're really targeting some sites where we think we can get data relatively quickly. Because we want to -- in these early stages, the most important thing is to generate the data as quickly as we can and prove that the triplet works. We've got a lot of preclinical data that suggests that IRAK4 is the primary driver of disease in half of all AML patients.

所以先說第一個。因此，對於三元組的初步研究，我們實際上針對的是一些我們認為可以相對快速地取得資料的網站。因為我們想要——在這些早期階段，最重要的是盡快產生數據並證明三元組是有效的。我們有大量臨床前數據表明，IRAK4 是半數 AML 患者疾病的主要驅動因素。

There's a published article, as you know, the Smith's Chaudhary article that was published in Nature in 2019, pointed that out. Half of all patients, this is the number one driver of disease. In the other half of patients, it's not the number one driver of disease, but it's a secondary or tertiary driver. So really this should provide incremental benefit from a new mechanism that no other drug does.

如你所知，有一篇發表的文章指出了這一點，即 2019 年發表在《自然》雜誌上的史密斯·喬杜里 (Smith's Chaudhary) 文章。在一半的患者中，這是疾病的第一大驅動因素。在另一半患者中，它不是疾病的第一大驅動因素，而是第二或第三驅動因素。因此，實際上，這應該可以從其他藥物無法做到的新機制中提供增量益處。

So the long-term to capture as many patients as we can is to, of course, go front-line in combination with standard of care that's azacitidine and venetoclax. So our hope would be that we can recapitulate in humans, what we've found in the lab and that is whether you add emavusertib to aza or to ven or the aza-ven combo. This significantly increases the efficacy of that standard of care treatment. So that's what we found in the lab. And again, that's what we want to try and identify very quickly, if possible in the clinic. And of course, we always want to check for safety.

因此，從長遠來看，我們要捕獲盡可能多的患者，當然就是結合阿扎胞苷和維奈托克的標準護理前往前線。因此，我們希望能夠在人類身上重現我們在實驗室中發現的情況，即是否將 emavusertib 添加到 aza、ven 或 aza-ven 組合中。這顯著提高了此標準護理治療的功效。這就是我們在實驗室中發現的。再說一遍，如果可能的話，我們希望在診所快速嘗試並識別出這一點。當然，我們總是想檢查安全性。

Aza and ven, as you know, are pretty tough regimen to tolerate. They're effective, but they're pretty tough to tolerate. Anecdotally half of all patients that go on that aza-ven doublet and have to discontinue treatment. So we're going to be doing in the early days is putting patients on and confirming that there is no safety overlap as we expect.

如你所知，Aza 和 ven 是非常難以忍受的養生法。它們很有效，但很難忍受。有趣的是，所有接受阿札維雙聯治療的患者中有一半不得不停止治療。因此，我們早期要做的就是讓患者配戴並確認不存在我們預期的安全重疊。

And then second, of course, we're going to be looking for that efficacy signal. And if you want to do that kind of exploration quickly, it really helps to identify the sites that you can focus on in a very concentrated way and those are the sites we've chosen to initiate that study. Your second question, could you remind me?

其次，當然，我們將尋找功效訊號。如果您想快速進行這種探索，那麼確定您可以以非常集中的方式關注的網站確實很有幫助，而這些網站就是我們選擇啟動研究的網站。你的第二個問題，可以提醒我一下嗎？

Yeah. That's fully understand. So on the PCNSL trial, so are you expecting to get front-line patients? If you want to get to that you want to combine with emavusertib or ibrutinib? What's the plan here?

是的。這樣就完全明白了。那麼在 PCNSL 試驗中，您期望獲得第一線患者嗎？如果您想達到這一目標，您想與 emavusertib 或 ibrutinib 結合使用嗎？這裡有什麼計劃？

Thank you. Thank you for that. So right now, the combination is emavusertib and ibrutinib and it's in relapsed refractory patients and that's the initial starting point. And again, the rationale for first the combination of ema and ibrutinib, that one's clear. In the case of lymphoma, the problem driving disease for patients with NHL is NF-kappa B overactivity. So when NF-kappa B is overactive, what happens is it disrupt the apoptotic process of the malignant cells.

謝謝。謝謝你。所以現在，emavusertib 和 ibrutinib 的組合用於復發難治性患者，這是最初的起點。再說一次，首先將 ema 和依魯替尼聯合使用的理由很清楚。就淋巴瘤而言，導致 NHL 患者患病的問題是 NF-κ B 過度活躍。因此，當 NF-κ B 過度活躍時，會破壞惡性細胞的凋亡過程。

So if you're on a BTK inhibitor today, the reason you're on that BTK inhibitor is that it blocks the BCR pathway, which is one of two pathways driving NF-kappa B overactivity. We now know that that's effective and you get a pretty high response rate on BTK inhibitors. And in fact, as you know, it's a $10 billion to $15 billion market today, ibrutinib itself is $10 billion of that, the AbbVie and J&J drug.

因此，如果您現在正在服用 BTK 抑制劑，那麼您服用 BTK 抑制劑的原因是它會阻斷 BCR 途徑，而 BCR 途徑是導致 NF-kappa B 過度活躍的兩條途徑之一。我們現在知道這是有效的，並且 BTK 抑制劑的反應率相當高。事實上，如您所知，如今這是一個 100 億至 150 億美元的市場，艾伯維 (AbbVie) 和強生 (J&J) 的藥物依魯替尼 (ibrutinib) 本身就是其中的 100 億美元。

What we are looking to do in lymphoma is hit NF-kappa B as hard as we can. There are now five big pharma companies that are chasing after BTK inhibitors of various flavors, covalent or non-covalent, all of them working effectively the same way, all of them blocking that BCR pathway driving NF-kappa B. The second pathway, the toll-like receptor pathway is currently unaddressed.

對於淋巴瘤，我們希望盡最大努力打擊 NF-kappa B。現在有五家大型製藥公司正在追逐各種口味（共價或非共價）的BTK 抑制劑，所有這些抑制劑都以相同的方式有效發揮作用，所有這些抑制劑都阻斷驅動NF-kappa B的 BCR 途徑。Toll樣受體途徑目前尚未解決。

Curis is the only company that has a drug that blocks that path that's emavusertib. It binds to MYD88 Myddosome and without that binding in the absence of IRAK4 Myddosome and the toll-like receptor path more broadly shutdown. So it stands to reason when you step back, if you have lymphoma that's effectively treated by BTK, you'll always want to block the NF-kappa B or down-regulate NF-kappa B as strongly as you can.

Curis 是唯一一家擁有能夠阻斷這一途徑的藥物（emavusertib）的公司。它與 MYD88 Myddosome 結合，並且在沒有 IRAK4 Myddosome 的情況下沒有這種結合，並且 Toll 樣受體路徑更廣泛地關閉。因此，退一步講，如果您患有 BTK 能有效治療的淋巴瘤，您總是希望盡可能強烈地阻斷 NF-kappa B 或下調 NF-kappa B。

So hit the BCR path with BTK, hit the toll-like receptor path with IRAK4. The combination not monotherapy, the combination should always be better than either one alone. And that's what we found in the lab and of course, that's what we're finding so far in the clinic. So that's the logic for the combination with emavusertib.

因此，用 BTK 擊中 BCR 路徑，用 IRAK4 擊中 toll 樣受體路徑。聯合療法不是單一療法，聯合療法應該總是比單獨使用任何一種療法更好。這就是我們在實驗室中發現的，當然，這也是我們迄今為止在診所中發現的。這就是與 emavusertib 結合的邏輯。

In terms of going to frontline, eventually, of course, we would like to suggest that the long-term possibility that we're going to explore is, is this an opportunity to have a companion front-line standard of care with BTK across non-Hodgkin's lymphoma? Now it's a little premature for that. We've chosen primary CNS lymphoma as our proof-of-concept indication to prove it out. And we've been able to show that we can generate data pretty quickly.

當然，就前往前線而言，最終我們想建議的是，我們要探索的長期可能性是，這是否是一個機會，可以在非非醫療領域與 BTK 建立配套的前線護理標準？-霍奇金淋巴瘤？現在說這個還為時過早。我們選擇原發性中樞神經系統淋巴瘤作為我們的概念驗證適應症來證明這一點。我們已經證明我們可以非常快速地產生數據。

But long-term, I think, of course, we're going to want to go frontline in combination with BTK inhibitors. For now having an ultra-orphan indication where we can go into the relapsed refractory setting where there are no drugs approved, that should offer a pretty compelling regulatory opportunity. So that's why we're going down that path. Pretty long answer, I hope that was helpful.

但從長遠來看，我認為我們當然會希望與 BTK 抑制劑聯合走在前線。目前，我們有一個超級孤兒適應症，可以進入沒有批准藥物的復發難治性環境，這應該提供一個非常引人注目的監管機會。這就是我們走這條路的原因。答案很長，希望對您有幫助。

No, we got it. And speaking of companion, since you're moving into the solid tumor, I'm curious if you are going to push forward the companion diagnostic for IRAK4 mutation assay, and if that would be helpful in carving the market both for inside the solid tumor space and also eventually in the leukemia setting?

不，我們明白了。說到伴隨診斷，既然你正在進入實體瘤領域，我很好奇你是否會推動 IRAK4 突變檢測的伴隨診斷，以及這是否有助於開拓實體瘤內部的市場太空以及最終在白血病環境中？

Yeah. So the short answer is yes, the long answer is it's a little more complicated. So that in the short answer, are we pursuing the identification and the regulatory path for a companion diagnostic for IRAK4 expression? And the answer is yes, absolutely. The more complicated answer is we don't want that to slow down our path to development and making this drug available for patients. So the way we're ensuring that fastest path is in monotherapy and leukemia side, where we're looking to go into patients that have either a FLT3 mutation or IRAK4 over expression.

是的。所以簡短的答案是肯定的，長期的答案是有點複雜。簡而言之，我們是否正在尋求 IRAK4 表達伴隨診斷的識別和監管路徑？答案是肯定的，絕對的。更複雜的答案是我們不希望這減慢我們的開發進程並使這種藥物可供患者使用。因此，我們確保最快路徑的方法是在單一療法和白血病方面，我們希望進入具有 FLT3 突變或 IRAK4 過度表達的患者。

We're going to focus the IRAK4 population using spliceosome mutations. Now spliceosome mutations are a subset of patients that overexpress IRAK4. And the reason why you'd go after spliceosome mutations is those mutations are already identified in existing gene panels.

我們將使用剪接體突變來關注 IRAK4 群體。現在，剪接體突變是過度表達 IRAK4 的患者的子集。你之所以要尋找剪接體突變，是因為這些突變已經在現有的基因組中被辨識出來。

So a companion diagnostic is much easier. We don't need to have a new assay identifying IRAK4. We can just lean into the existing panels the Illumina panel, the FoundationOne panel, places like MD Anderson that have a proprietary gene panels. These panels are already run on their existing patients. And we can lean into that and say, if you have one of these specific mutations by definition, you have IRAK4 expression, and use that as our mechanism. But longer term, of course, we're going to want a diagnostic. It's the logic for going frontline in combination. We're going to go all comers where we won't need a companion diagnostic.

因此伴隨診斷就容易得多。我們不需要新的檢測方法來識別 IRAK4。我們可以依靠現有的面板，例如 Illumina 面板、FoundationOne 面板，以及 MD 安德森等擁有專有基因面板的地方。這些面板已經在現有患者身上運行。我們可以根據這一點說，如果根據定義你有這些特定突變之一，你就有 IRAK4 表達，並將其用作我們的機制。但從長遠來看，當然，我們需要診斷。這就是組合上前線的邏輯。我們將去所有不需要伴隨診斷的地方。

Thank you again, for taking all the questions and congrats on the progress.

再次感謝您提出所有問題並祝賀我們的進展。

Sure. Thank you.

當然。謝謝。

Li Watsek, Cantor Fitzgerald.

李‧沃塞克，坎托‧費茲傑拉。

Hey, good morning. Thanks for taking my questions. Jim, I guess for the data that you're going to present from the Leukemia study around midyear, maybe just set the expectations for us a little bit with data set that we are going to see, what the bar is for the three as well as for spliceosome mutations? And then for the combo data that's going to come second half of this year, maybe tell us a little bit about the bar here. Because each event as we know the bar is fairly high, pretty effective. And also, as you alluded to earlier about toxicities and do you expect any overlapping talks with this regimen?

嗨，早安。感謝您回答我的問題。吉姆，我想對於你將在年中左右提供的白血病研究數據，也許只是用我們將要看到的數據集為我們設定一點期望，這三個人的標準是什麼至於剪接體突變？然後，對於今年下半年將發布的組合數據，也許可以告訴我們一些關於這裡的酒吧的資訊。因為據我們所知，每個活動的門檻都相當高，而且非常有效。而且，正如您之前提到的有關毒性的問題，您是否期望與該方案有任何重疊的討論？

Yeah. Thank you, Li. Appreciate you dialing in. So on those questions, first, in terms of the number of patients, we've consistently said what we'd like to have is a dataset of 10 to 20 patients. We now have a dataset of three patients, in spliceosome three patients in FLT3 at our target dose and five patients, of course, in primary CNS. We'd like to increase that dataset equals 20 to 50, somewhere in that range.

是的。謝謝你，李。感謝您撥入。因此，對於這些問題，首先，就患者數量而言，我們一直表示我們希望擁有 10 到 20 名患者的資料集。我們現在擁有三名患者的數據集，在剪接體中，三名患者處於我們目標劑量的 FLT3 中，當然還有五名患者處於原發性中樞神經系統中。我們希望將該資料集增加到 20 到 50（在該範圍內的某個位置）。

I hope that we're going to be in a position, where we've got data collected. Of course, you enroll the patients and treat them, follow them for a period of time and then assess the responses. My hope is that we would have to be in a position to have that level of and that level of data in leukemia, spliceosome, and FLT3 by midyear and in lymphoma by year-end.

我希望我們能夠收集到數據。當然，你會招募患者並治療他們，追蹤他們一段時間，然後評估反應。我的希望是，我們必須能夠在年中之前獲得白血病、剪接體和 FLT3 方面的數據，並在年底前獲得淋巴瘤的數據。

In terms of the benchmark, what we think we need to do to be effective in the monotherapy side is, we're targeting a CR/CRh of 20% lower bound in the low-teens, 12%, 13% kind of lower bound. But at a 20% CR/CRh rate in salvage line therapy for either FLT3 or spliceosome in leukemia, we think is very compelling. Of course, our first three patients look better than that, but let's not get ahead of ourselves. It's only three patients as we get to 10 to 20 patients, what we'd really hope is that we can clear that CR/CRh rate of 20% and [Vietnam].

就基準而言，我們認為要在單一療法方面發揮作用，我們的目標是 CR/CRh 的下限為 20%，下限為 12%、13% 。但在白血病中，FLT3 或剪接體的挽救線療法的 CR/CRh 率為 20%，我們認為這是非常引人注目的。當然，我們的前三位患者看起來比這要好，但我們不要操之過急。現在只有 3 名患者，而我們有 10 到 20 名患者，我們真正希望的是我們能夠清除 20% 的 CR/CRh 率，[越南]。

On the lymphoma side, because there are no existing treatments. And that bar is probably lower. What we do know is that the largest data set available for BTK as a monotherapy in primary CNS lymphoma was a study of 52 patients, the CR rate was 19, you'd expect one out of five patients or were again, roughly a 20% CR rate in that population. And that's in BTKi-naïve patients. Once they've failed BTK, you'd expect that re-challenging them with BTK yet again, probably wouldn't work at all. You might expect zero out of five. That we are getting three out of five so far is obviously highly encouraging.

在淋巴瘤方面，因為沒有現有的治療方法。而且這個門檻可能更低。我們所知道的是，BTK 作為原發性 CNS 淋巴瘤單一療法的最大數據集是一項針對 52 名患者的研究，CR 率為 19，您預計五分之一的患者或再次大約是 20%該人群的CR 率。這是在未使用過 BTKi 的患者中。一旦他們在 BTK 上失敗了，你會認為再次用 BTK 挑戰他們可能根本行不通。您可能期望五分之零。到目前為止，我們已經得到了五分之三，這顯然非常令人鼓舞。

I don't think we need to maintain quite that rate. But if we can maintain in BTK experience patients a 20% or higher CR rate in lymphoma, I think that we've got a very compelling data set, have a discussion with FDA. So 10 to 20 patients in all indications, is what we're hoping for. We look to be in a position to have data in that range for leukemia by midyear and for lymphoma by year-end. Was that helpful?

我認為我們不需要保持這個速度。但如果我們能夠在 BTK 經驗患者中維持 20% 或更高的淋巴瘤 CR 率，我認為我們已經獲得了非常令人信服的數據集，可以與 FDA 進行討論。所以我們希望有 10 到 20 位所有適應症的患者。我們希望能夠在年中之前獲得該範圍內的白血病數據，並在年底之前獲得淋巴瘤的數據。這樣有幫助嗎？

And overlapping toxicities with [aza-ven]?

和重疊的毒性[阿札文]？

Yes. So that's the number one thing to look for in the triplet. Of course, it makes sense that if you looked at our preclinical data and we've got a really nice outline of the preclinical data in our corporate deck, it's very clear that from an efficacy perspective, in the lab, we were able to add efficacy to aza to aza-ven. And it looks like it's the consistency that we saw from mechanism to lab to clinic works the same way in the leukemia triplet, that it's worked everywhere else we've tested.

是的。所以這是在三元組中要尋找的第一件事。當然，這是有道理的，如果您查看我們的臨床前數據，並且我們在公司平台中獲得了非常好的臨床前數據概述，那麼很明顯，從功效的角度來看，在實驗室中，我們能夠添加aza 至 aza-ven 的功效。看起來我們看到從機製到實驗室再到診所的一致性在白血病三聯體中以同樣的方式起作用，並且它在我們測試過的其他地方都有效。

We would expect to see that the part that I'd say really merits some exploration is making sure knowing that the toxic is high in aza-ven, that we don't add to it. We don't have any reason to believe that adding emavusertib would make it less tolerable based on what we know. There is no overlapping safety profile.

我們希望看到我想說的真正值得探索的部分是確保知道氮雜文中的毒性很高，我們不會添加到其中。根據我們所知，我們沒有任何理由相信添加 emavusertib 會使其變得更難以容忍。不存在重疊的安全配置。

However, as we said, half of all patients that go on to aza-ven have difficulty tolerating it. First thing we're going to look for as we add our drugs to aza-ven is to make sure we're not exacerbating those toxicities. And of course, efficacy, you always look for but first things first, let's make sure that we've got a drug that's tolerable in combination.

然而，正如我們所說，所有接受 aza-ven 治療的患者中有一半難以耐受。當我們將藥物添加到 aza-ven 中時，我們要做的第一件事是確保我們不會加劇這些毒性。當然，你總是在尋找療效，但首先，讓我們確保我們擁有一種可以耐受合併用藥的藥物。

And what are your thoughts on the maintenance setting in AML? Are you collecting any data points that could potentially maybe support off-label use?

您對 AML 中的維護設定有何看法？您是否正在收集任何可能支援標籤外使用的資料點？

Well, obviously, off-label use is something that happens, but companies don't target that. What we do look for is do we have a drug that first and foremost is safe. Second has a compelling and unique efficacy profile, so that we can provide a measure of efficacy that you can't get from other drugs.

嗯，顯然，標籤外使用是會發生的事情，但公司並沒有瞄準這一點。我們首先要尋找的是安全的藥物。Second 具有令人信服且獨特的療效特徵，因此我們可以提供其他藥物無法獲得的療效衡量標準。

And then third to your point, you want to make sure you've got a drug that can be taken chronically for long periods of time. Some of the indications we're going after like AML are fairly aggressive, but others like Waldenström's are quite indolent. And we have a patient that's been on drug for I believe over four years now. So we've got a great track record. These are still early days of drug development from emavusertib, but I think so far, we've been able to check all three boxes.

第三，你要確保你有一種可以長期長期服用的藥物。我們正在尋找的一些適應症（例如 AML）相當具有侵略性，但其他適應症（例如華登斯特羅姆氏症）則相當惰性。我們有一位患者，我相信已經服藥四年多了。所以我們有很好的記錄。目前仍處於 emavusertib 藥物開發的早期階段，但我認為到目前為止，我們已經能夠檢查所有三個框架。

The drug looks in almost 200 patients tested to have a really good safety profile. And it looks as though it does provide in humans, the same kind of clinical efficacy that we were seeing in the lab. And it looks as though you can take this drug over a long period of time in a maintenance setting. And that's, of course, that's the trifecta that you hope for as a drug developer.

該藥物在近 200 名患者的測試中顯示出非常好的安全性。看起來它確實為人類提供了與我們在實驗室中看到的相同的臨床功效。看起來你可以在維持環境中長期服用這種藥物。當然，這就是您作為藥物開發商所希望的三連勝。

Thank you.

謝謝。

Yale Jen, Laidlaw & Company.

耶魯‧詹 (Yale Jen)，萊德勞公司。

Good morning and thanks for taking the question. Jim, you have talked about that you would be interested to move to MDS, high-risk MDS, the second line but you're waiting for the VERONA study readout. Just to your best knowledge, when do you think that might happen and what -- and if that take place sometime in the future? And what's your plan at this point?

早上好，感謝您提出問題。Jim，您曾說過您有興趣轉向 MDS、高風險 MDS、第二線，但您正在等待 VERONA 研究結果。據您所知，您認為這種情況何時會發生以及會發生什麼——如果這種情況發生在未來某個時候？此時你的計劃是什麼？

Yeah. Thank you, Yale. I appreciate the question. So you're exactly right. And the opportunity in MDS looks terrific. The clinical data that we've put out so far looks as though in MDS, just as it did in AML and just as it has in lymphoma, it appears as though this drug has a single agent is active. It provides unique and compelling anticancer activity. We would really like to do in MDS what we're doing in leukemia, which is go frontline in combination with standard of care and see whether or not we can provide benefits.

是的。謝謝你，耶魯。我很欣賞這個問題。所以你是完全正確的。MDS 的機會看起來非常好。到目前為止，我們公佈的臨床數據看起來就像在 MDS 中一樣，就像在 AML 中一樣，就像在淋巴瘤中一樣，似乎這種藥物只有一種藥物是有效的。它提供獨特且引人注目的抗癌活性。我們真的很想在骨髓增生異常綜合徵方面做我們在白血病方面所做的事情，即與標準護理相結合，走在前線，看看我們是否可以提供好處。

Can this really add to the effectiveness of standard of care? Well in AML we know what the standard of care is. It's aza-ven. I think MDS development has just gone a little slower with aza-ven and a lot of people were expecting it might have read out this past to ASH.

這真的能提高護理標準的有效性嗎？在 AML 中，我們知道護理標準是什麼。這是阿札文。我認為 aza-ven 的 MDS 開發速度稍微慢了一些，很多人都期待它可能已經向 ASH 讀出了這段過去。

Now people are looking for ASCO to be frank. We don't know any more than you do of when those are going to readout, but we do expect it's imminent. And the answer is standard of care in MDS is going to be either aza or the aza-ven doublet. If VERONA read outs positively it's aza-ven; if it reads out negatively it's aza.

坦白說，現在人們正在尋找 ASCO。我們和你們一樣不知道這些數據何時會被讀出，但我們確實預期它即將到來。答案是 MDS 的護理標準將是 aza 或 aza-ven doublet。如果 VERONA 讀數為正，則為 aza-ven；如果讀數為負，則為 aza。

And what we want to know is which of those two wins, if you like, so that we can then initiate a combo, whether it's a doublet or a triplet to see whether we can add benefit to that population in the front-line setting. So we are eagerly anticipating it as you are, and as soon as we have those results, we'll be looking to initiate a front-line study in combination in MDS as well.

如果你願意的話，我們想知道的是這兩個中的哪一個獲勝，以便我們可以啟動一個組合，無論是雙人組合還是三組合，看看我們是否可以為前線環境中的人群增加福利。因此，我們和您一樣熱切地期待著它，一旦我們得到這些結果，我們也將尋求啟動一項 MDS 聯合一線研究。

Okay. Great. That's very helpful. And my second question here is that earlier we thought --we were sort of expecting that you guys may conduct a meeting with FDA to talk about the next stage of development after the AML data. Do you anticipate this meeting could happen much later this year or you anticipate this potentially be a 2025 event?

好的。偉大的。這非常有幫助。我的第二個問題是，早些時候我們認為——我們有點期待你們可以與 FDA 舉行會議，討論 AML 數據後的下一階段的開發。您預計這次會議可能會在今年稍後舉行，還是預計可能會在 2025 年舉行？

So I really can't speak on behalf of the FDA, how quickly we're going to have that meeting. We are, of course, very interested in having it as soon as possible. I think we have the kind of drug that the FDA should likely be as interested in as all of our investigators are. And that is, we've got a drug that has a great safety profile, that really seems to add efficacy wherever we're testing it and may be able to provide benefit in areas like second-line PCNSL, where there are no drugs approved.

所以我真的不能代表 FDA 發言，我們要多快召開這次會議。當然，我們非常有興趣盡快擁有它。我認為 FDA 應該像我們所有的研究人員一樣對我們的藥物感興趣。也就是說，我們擁有一種具有良好安全性的藥物，無論我們在哪裡測試它，它似乎都確實增加了療效，並且可能能夠在二線 PCNSL 等領域提供益處，在這些領域還沒有批准藥物。

The FDA ought to be receptive to that. So as soon as we can get a sufficient number of patients together, and it's probably in that 10 to 20 range, depending upon what kind of results we're getting. If the results are consistent moving forward to what we've seen in the past, we'd be looking to have a meeting with FDA as soon as we can.

FDA 應該對此表示接受。因此，一旦我們能夠聚集足夠數量的患者，可能會在 10 到 20 個範圍內，這取決於我們得到的結果類型。如果結果與我們過去所看到的一致，我們將盡快與 FDA 舉行會議。

And then of course, as you know, the FDA has got a lot of guidelines about when you apply and how quickly they have those meetings. But we'd be somewhat subject to the FDA's scheduling on their end. But we look really forward to being able to tell you when we've got that call on the docket, so that we can push forward these drugs as quickly as possible.

當然，如您所知，FDA 對於您何時申請以及他們召開這些會議的速度有很多指導方針。但我們在某種程度上會受到 FDA 的日程安排的影響。但我們真的很期待能夠在接到電話後通知您，以便我們能夠盡快推出這些藥物。

Okay. Great. Maybe just tackle one last housekeeping question. I know you guys do not typically give guidance in terms of the operating expenses, but could you give more directional suggestion in terms of the operating expenses this year 2024, comparing to 2023? And thanks.

好的。偉大的。也許只是解決最後一個內務問題。我知道你們通常不會在營運費用方面提供指導，但與 2023 年相比，你們能否就 2024 年的營運費用提供更多指導性建議？謝謝。

Yeah, why don't I ask Diantha to chime in on that.

是啊，我為什麼不請戴安莎插話一下呢。

Thanks, Jim. So yeah, I mean, we believe that our operating expenses are going to remain relatively consistent. As we've guided, the $56 million of cash gets us into '25. So that gives us the burn rate in kind of 10% to 12% may peak up to 13%, depending on timing of some manufacturing and other things that tend to be a little bit more chunky. But I think you should expect it to be fairly consistent year over year.

謝謝，吉姆。所以，是的，我的意思是，我們相信我們的營運費用將保持相對穩定。正如我們所指導的那樣，5600 萬美元的現金讓我們進入了 25 世紀。因此，這給了我們 10% 到 12% 的燃燒率，峰值可能高達 13%，具體取決於某些製造的時間安排和其他往往更粗的事情。但我認為你應該期望它每年都相當一致。

Okay. Great. Thanks a lot, and congrats on the development and look forward to the data readout.

好的。偉大的。非常感謝，恭喜開發，期待數據讀出。

Thank you.

謝謝。

Bill Jahangiri, Truist Securities.

比爾‧賈漢吉里 (Bill Jahangiri)，Truist 證券公司。

Hi, congratulations. Thanks for taking my questions. We were wondering if there were any -- if you could tell us anything about strategic or partnership interest at JPM from year end. And then also for the triplet study in AML for the patients you're enrolling. Could you just remind us what the bars would be for that one? Thank you.

你好，恭喜你。感謝您回答我的問題。我們想知道是否有任何 - 您能否告訴我們有關摩根大通從年底開始的戰略或合作夥伴關係的任何信息。然後還有針對您招募的患者的 AML 三聯體研究。可以提醒我們一下那個酒吧的酒吧是什麼嗎？謝謝。

Sure. Thanks, Bill. So as you can imagine the interest that we've seen on the partnering side, kind of mirrors the interest that we've got in the investigator side participating in our trials. And we of course, are always having conversations with potential partners. And at some point, I think many people would like to imagine that if we can go broadly with this drug everywhere where we think it could work. So that's across lymphoma in areas wherever BTK gets used in leukemia, AML and MDS in the frontline setting and now in solid tumors.

當然。謝謝，比爾。因此，正如您可以想像的那樣，我們在合作方看到的興趣，某種程度上反映了我們對參與我們試驗的研究者一方的興趣。當然，我們一直在與潛在合作夥伴進行對話。在某些時候，我想很多人都會想像，如果我們能夠在我們認為有效的任何地方廣泛使用這種藥物。因此，BTK 在前線治療白血病、AML 和 MDS 的領域以及現在在實體瘤中使用的領域都適用於淋巴瘤。

We just started in melanoma. But as I mentioned, there are a number of other solid tumor indications that have been studied with our drug by NCI and academic centers. And Curis can't afford -- we're too small, we can't afford to run studies in all those areas.

我們剛開始研究黑色素瘤。但正如我所提到的，NCI 和學術中心已經用我們的藥物研究了許多其他實體瘤適應症。庫里斯負擔不起——我們太小了，我們無法承擔所有這些領域的研究。

At some point, it's going to make sense to turbocharge those clinical efforts with the help of a partner both with bank book and manpower. Going forward, I think it's unlikely that we're going to strike a deal as we did in melanoma where we don't have to give up any rights and we get just providing drug, we get data. But I think at some point that will make sense. And I would say, we're not giving guidance on timing for that, but I'd say stay tuned. This looks to be a really compelling drug and Curis is not the only company that's recognized that. And could you remind me, Bill, the second part of your question?

在某種程度上，在擁有銀行存款和人力的合作夥伴的幫助下，推動這些臨床工作將是有意義的。展望未來，我認為我們不太可能像在黑色素瘤方面那樣達成協議，我們不必放棄任何權利，我們只需提供藥物，我們即可獲得數據。但我認為在某些時候這是有道理的。我想說，我們不會就具體時間提供指導，但我想說，請繼續關注。這看起來是一種非常引人注目的藥物，Curis 並不是唯一一家認識到這一點的公司。比爾，你能提醒我你問題的第二部分嗎？

Yes, the triplet. So I'm not really sure what the patients look like and the eligibility criteria. So I was wondering if you could just tell us like what the bar would be for success there and some just overall benchmarks.

是的，三胞胎。所以我不太確定患者的樣子和資格標準。所以我想知道您是否可以告訴我們成功的標準是什麼以及一些總體基準。

Right. Thank you. Yes, I think as I mentioned to Li Watsek at Cantor, I think the bar really is a safety bar in the early days. We are cognizant that the doublet of aza-ven is difficult for patients to tolerate. When we look at the drugs we're combining with, whether it's aza-ven or ibrutinib for that matter, these are all drugs that they're effective. But their safety profiles are tough.

正確的。謝謝。是的，我想正如我向 Cantor 的 Li Watsek 提到的那樣，我認為這個酒吧在早期確實是一個安全酒吧。我們認識到患者很難耐受 aza-ven 的雙聯體。當我們觀察我們所合併使用的藥物時，無論是 aza-ven 還是 ibrutinib，這些藥物都是有效的。但它們的安全性非常嚴格。

And so the first order of business, if we're going to combine with those, we want to make sure that we don't take a difficult regimen to tolerate and may get worse. So first things first. There's no reason to believe we have an overlap of safety profile, but we need to test that out in patients and make sure that, that's so. It's easily the thing we're looking for first. Now of course, whenever you're looking for safety, once you pass that hurdle, you're going to be looking for signs of efficacy.

因此，首要任務是，如果我們要將這些結合起來，我們要確保我們不會採取難以忍受的治療方案，並且可能會變得更糟。所以首先要做的事情。沒有理由相信我們的安全性有重疊，但我們需要在患者身上進行測試並確保確實如此。這很容易就是我們首先要尋找的東西。當然，現在，每當您尋求安全性時，一旦您跨越了這個障礙，您就會尋找功效的跡象。

And we're going to want to be able to see that we can replicate in the clinic with the triplet what we've been able to do in all of our other studies to-date, and that is recapitulate the preclinical experience and show that adding emavusertib, that addressing this novel driver of cancer in IRAK4, that addressing that target does yield incremental efficacy above and beyond current standard of care. And if we can do that, I think that's the home run. So first things first, safety. But of course, we're going to look for efficacy as well. Hopefully, that's helpful.

我們希望能夠看到我們可以在臨床上用三聯體複製我們迄今為止在所有其他研究中所做的事情，那就是概括臨床前經驗並表明補充道，emavusertib 解決了IRAK4 中癌症的新驅動因素，解決該目標確實產生了超出目前護理標準的增量療效。如果我們能做到這一點，我認為這就是本壘打。所以首先，安全。但當然，我們也會尋找功效。希望有幫助。

That's wonderful.

那好極了。

Yes.

是的。

And I guess one last one. I just want to verify, make sure I'm not thinking about this incorrectly. It seems like you're already hitting the duration bar in CNS lymphoma, right? We just need that data set to grow.

我猜還有最後一個。我只是想驗證一下，確保我沒有錯誤地思考這個問題。看來您已經達到中樞神經系統淋巴瘤的治療期限，對吧？我們只需要該資料集增長。

Yeah. I think it's exactly right. I think the data set looks fantastic. In fact, it was quite a bit better than we would need. But it’s early days, stand up five. So as we go to 10 and then to 20 patients, as I said, I think what we need to be able to show, if you had 20 patients with primary CNS lymphoma, that you were treating that had failed high-dose methotrexate and chemo. Today they're going to go on BTK. They're going to go on ibrutinib. You'd expect 4 of those 20 patients to get a response based on the largest study that's been done on ibrutinib monotherapy, CR rate of 19.

是的。我認為這是完全正確的。我認為該數據集看起來很棒。事實上，它比我們需要的要好得多。但現在還早，五人起立。因此，正如我所說，當我們研究10 名然後是20 名患者時，我認為我們需要能夠證明，如果您有20 名原發性中樞神經系統淋巴瘤患者，那麼您正在治療的高劑量甲氨蝶呤和化療失敗了。今天他們將繼續使用 BTK。他們將繼續服用依魯替尼。根據對依魯替尼單藥療法進行的最大研究，您預計這 20 名患者中有 4 名會獲得緩解，CR 率為 19。

So let's round up a little bit, call it 20, you'd need 4 CRs out of 20 patients. In our case we're three of five. We need to add 15 more patients and get one more CR just to match the earlier line. Because remember, all of our patients who had failed ibrutinib, you'd expect 0 out of 20, if you rechallenge them with ibrutinib. So in our case, if we can match that prior line of get 4 out of 20, or one more CR out of the next 15 patients. I think we've got a really compelling discussion to have with FDA. And I think frankly, our odds are pretty good at that.

因此，讓我們四捨五入一下，稱之為 20，您需要 20 名患者中有 4 名 CR。就我們而言，我們是五人中的三人。我們需要再增加 15 名患者並再獲得 1 名 CR，以匹配先前的線路。因為請記住，我們所有依魯替尼失敗的患者，如果您用依魯替尼重新挑戰他們，您預計 20 例中的​​ 0 例。因此，在我們的例子中，如果我們能夠匹配先前的路線，即從 20 名患者中獲得 4 名患者，或從接下來的 15 名患者中再獲得 1 名 CR。我認為我們與 FDA 進行了一次非常引人注目的討論。坦白說，我認為我們的勝算很大。

Great. Thank you.

偉大的。謝謝。

You bet.

你打賭。

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, Jim Dentzer for any closing remarks.

我們的問答環節到此結束。我想將會議轉回公司總裁兼執行長 Jim Dentzer 致閉幕詞。

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

謝謝你，安德里亞。感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 Curis 團隊的辛勤工作和承諾，感謝 Aurigene 和 NCI 的合作夥伴持續提供的幫助和支持。我們期待盡快再次為您提供最新消息。操作員？

The conference has now concluded. Thank you for attending today's presentation and you may now disconnect.

會議現已結束。感謝您參加今天的演示，您現在可以斷開連接了。