Curis Inc (CRIS) 2024 Q3 法說會逐字稿

Good morning, ladies and gentlemen and welcome to the Curis third quarter, 2024 business update call at this time. All lines are in a listen-only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call, you require immediate assistance. Please press star zero for the operator. This call is being recorded on Thursday, November 14, 2024. I would now like to turn the conference over to Diantha Duvall. Curis Chief Financial Officer. Please go ahead.

早安，女士們、先生們，歡迎此時參加 Curis 2024 年第三季業務更新電話會議。所有線路均處於僅監聽模式。演講結束後，我們將進行問答環節。如果在通話期間的任何時間您需要立即協助。請為操作員按星零。此電話錄音於 2024 年 11 月 14 日星期四進行。我現在想把會議交給黛安莎·杜瓦爾。庫里斯首席財務長。請繼續。

Thank you and welcome to Curis third quarter 2024 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 third quarter, 2024 business update, press 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 upon 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.

感謝您並歡迎參加 Curis 2024 年第三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 2024 年第三季的業務更新、新聞稿和相關財務表格。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。如需了解更多詳情。請參閱我們向 SEC 提交的文件。

Joining me on today's call are James 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 the call, I'd now like to turn the call over to James.

與我一起參加今天電話會議的有總裁兼執行長 James Dentzer 和首席開發長 J​​onathan Zung。我們還將在通話結束時進行問答環節，我現在想將通話轉給詹姆斯。

Thank you, Diantha. Good morning, everyone and welcome to Curis third quarter business update call.

謝謝你，黛安莎。大家早上好，歡迎致電 Curis 第三季業務更新。

Let's start with our take a Lymphoma study which is evaluating Emert in combination with Ibrutinib in relapsed refractory PCNSL patients that have failed after treatment with the BTK inhibitor.

讓我們從一項淋巴瘤研究開始，該研究正在評估 Emert 與依魯替尼聯合用於治療 BTK 抑制劑治療失敗的複發難治性 PCNSL 患者。

These patients are generally treated with a methotrexate based regimen which includes chemo or radiation in the frontline setting followed by a BTK inhibitor. When a patient's disease progresses, it's when this treatment fails in the salvage line setting, that patients become eligible to enroll in our study and receive m of user in combination.

這些患者通常接受基於甲氨蝶呤的治療方案，其中包括在前線進行化療或放療，然後使用 BTK 抑制劑。當患者的疾病進展時，當這種治療在挽救線設置中失敗時，患者就有資格參加我們的研究並接受 m 名用戶的聯合治療。

The thesis for this combination, which is supported by both preclinical data and our early clinical data is that blocking both of the pathways driving NHL, blocking the TLR pathway with [M OFER] and blocking the BCR pathway with Ibrutinib can enable patients to achieve an objective response. Even after they've progressed on Ibrutinib in September. At the third annual Ibrutinib four symposium in cancer.

這種組合的論點得到了臨床前數據和我們的早期臨床數據的支持，即阻斷驅動NHL 的兩條途徑，用[M OFER] 阻斷TLR 途徑，用依魯替尼阻斷BCR 途徑可以使患者實現客觀回應。即使他們在 9 月使用依魯替尼（Ibrutinib）取得了進展。在第三屆依魯替尼癌症四年研討會上。

We released an update of our PCNSL data with 10 evaluable patients.

我們發布了包含 10 名可評估患者的 PCNSL 數據的更新。

These data showed three complete responses. CRS, one unconfirmed, complete response. CRU and two partial responses were PRS the duration of response for three of the four patients with a CRS or CRS was greater than six months.

這些數據顯示了三個完整的回應。CRS，一種未經確認的完整回覆。CRU 和兩個部分緩解是 PRS，四名 CRS 患者中的三名或 CRS 患者的緩解持續時間超過六個月。

These data are very early but also encouraging, especially given the high unmet need in this population.

這些數據非常早期，但也令人鼓舞，特別是考慮到該族群的需求未被滿足。

We continue to enroll patients in this study and are actively engaging with regulatory authorities to gain alignment on the registrational path.

我們將繼續招募患者參與這項研究，並積極與監管機構合作，以在註冊路徑上取得一致。

As a reminder, this study is being run in the US Europe and Israel.

提醒一下，這項研究正在美國、歐洲和以色列進行。

It goes without saying that defining the registrational path to approval is a critical next step in Emavusertib development. And I'm pleased with the progress we're making.

不言而喻，定義核准的註冊路徑是 Emavusertib 開發的關鍵下一步。我對我們所取得的進展感到滿意。

Now, let's move on to our take a leukemia study which is evaluating Emert as monotherapy in patients with relapsed refractory AML at ASCO and EHA earlier this year, we provided updated data for patients with a flip three mutation.

現在，讓我們繼續進行一項白血病研究，該研究正在今年稍早在 ASCO 和 EHA 評估 Emert 作為復發難治性 AML 患者的單一療法，我們為具有翻轉三突變的患者提供了最新數據。

These data showed six of 11 evaluable patients achieved an objective response including three CRS one CRh and two MLFS.

這些數據顯示，11 名可評估患者中有 6 名獲得了客觀緩解，其中包括 3 例 CRS、1 例 CRh 和 2 例 MLFS。

Also of note, three of the 11 patients were naive to treatment with a fly three inhibitor. All three of these patients achieved an objective response and three of the remaining eight patients, those who had failed prior treatment with a fleet three inhibitor achieved an objective response at the ash meeting next month, an expanded data set of 19 responsive valuable patients will be presented by Derek by Dr,.Eric S. Winer from Dana Farber. In an oral presentation on Monday, December 9th, we will also be providing updated data for our study in patients with high risk MDs in a poster by lead author Dr.Guillermo Garcia-Manero from MD Anderson being presented on Sunday, December 8th overall. I'm very pleased with the progress in both our, take a leukemia and take a lymphoma studies.

另外值得注意的是，11 名患者中有 3 名未曾接受過果蠅 3 抑制劑治療。所有三名患者均取得了客觀緩解，其餘8 名患者中的3 名（之前使用三類抑製劑治療失敗的患者）在下個月的灰燼會議上取得了客觀緩解，將有19 名有反應的有價值患者的擴展資料集由Derek、Eric 博士介紹來自 Dana Farber 的 S.Winer。在12 月9 日星期一的口頭報告中，我們還將在12 月8 日星期日發布的海報中提供我們對高風險MD 患者的研究的最新數據，該海報由來自MD 安德森的主要作者Guillermo Garcia- Manero 博士提供。我對我們的白血病和淋巴瘤研究的進展感到非常高興。

And I look forward to providing additional updates as the year progresses with that, I'll turn the call over to Diantha for the financial update. Diantha.

我期待著隨著時間的推移提供更多更新，我將把電話轉給 Diantha 以獲取財務更新。石竹。

Thank you, James Curis reported a net loss of 10.1 million or a dollar 70 per share for the third quarter of 2024. Compared to a net loss of 12.2 million or $2.13 per share for the same period in 2023 pure supported a net loss of 33.8 million or $5.77 per share for the nine months ended September 30th, 2024 compared to a net loss of $35.7 million or $6.96 per share for the same period. In 2023 research and development expenses were 9.7 million for the third quarter of 2024. Compared to 10.4 million. For the same period. In 2023 the decrease was primarily attributable to lower consulting and employee related costs.

謝謝，James Curis 報告 2024 年第三季淨虧損 1,010 萬美元，即每股 70 美元。與2023 年同期的淨虧損1,220 萬美元或每股2.13 美元相比，截至2024 年9 月30 日的九個月，Pure 支持的淨虧損為3,380 萬美元或每股5.77 美元，而淨虧損為3,570萬美元或每股6.96 美元同期份額。2023年研發費用為2024年第三季970萬。相比之下，有 1040 萬。同一時期。2023 年下降的主要原因是諮詢和員工相關成本降低。

R&D expenses were 29.6 million for the nine months ended September 30th, 2024 compared to 29.5 million for the same period in 2023.

截至2024年9月30日的九個月，研發費用為2,960萬美元，而2023年同期為2,950萬美元。

General and administrative expenses were 38 were 3.8 million for the third quarter of 2024. Compared to 4.8 million for the same period. In 2023 the decrease was primarily attributable to lower legal and employee related costs.

2024年第三季一般及管理費用為380萬。同期為 480 萬。2023 年下降的主要原因是法律和員工相關成本降低。

DNA expenses were 13.4 million for the nine months ended September 30th, 2024 compared to 13.8 million for the same period. In 2023 in October, we completed a registered direct offering and concurrent private placement of unregistered warrants with net proceeds of approximately 10.8 million including the impact of the October 2024 offerings, Curis cash and cash equivalents totaled 31.6 million and the company had approximately 8.5 million shares of common stock outstanding.

截至 2024 年 9 月 30 日的九個月，DNA 費用為 1,340 萬美元，而同期為 1,380 萬美元。2023 年10 月，我們完成了註冊直接發行和未註冊認股權證同步私募，淨收益約為1080 萬股（包括2024 年10 月發行的影響），Curis 現金和現金等價物總計3160 萬股，公司擁有約850 萬股股票已發行普通股。

Harris expects its existing cash and cash equivalents will enable its planned operations into mid 25.

Harris 預計，現有現金和現金等價物將使其計劃營運持續到 25 年中期。

With that. I'd like to turn the call over for questions, operator.

就這樣。接線員，我想轉接電話詢問問題。

Thank you, ladies and gentlemen, we will now begin the question answer session. Should you have a question? Please press star followed by number one on your touchtone phone. You'll hear a prompt that your hand has been raised. Should you wish to decline from the holding process? Please press star followed by number two. If you are using a speaker phone, please leave the handset before pressing any keys.

謝謝各位，女士們、先生們，我們現在開始問答環節。你應該有一個問題嗎？請在您的按鍵式電話上按星號，然後按數字一。您會聽到提示音，表示您已舉手。您是否希望拒絕保留流程？請按星號，然後按數字二。如果您使用免持電話，請在按任何按鍵之前離開聽筒。

Once again to ask a question, please press star followed by number one on your Touchstone phone you will hear a prompt that your hand has been raised one moment, please. For your first question, your first question comes from the line of Edward White from H.C. Wainwrigh. Your line is now open. Please ask your question.

再次提問，請在 Touchstone 手機上按星號，然後按數字 1，您將聽到提示，請您舉手一會兒。對於你的第一個問題，你的第一個問題來自 H.C. 的愛德華懷特 (Edward White)。溫萊特。您的線路現已開通。請提出你的問題。

Good morning. Thanks for taking my questions.

早安.感謝您回答我的問題。

Good morning, James. So you had mentioned that you're working to gain alignment with the FDA and PCNSL. So that, you know, sort of implies that you're out of alignment. So what needs to be done right now to get into alignment? And what is the ideal pathway to approval in your mind?

早安，詹姆斯。您提到您正在努力與 FDA 和 PCNSL 保持一致。所以，你知道，這有點暗示你不協調。那麼現在需要做什麼才能保持一致呢？您心目中獲得認可的理想途徑是什麼？

Sure. So I wouldn't say we're out of alignment by any stretch. No, I just say we're engaging in the discussions. I think what, what we see and we've said this in the past on calls in the early days earlier this year, as we started to get the first data in on these patients, we saw that we were seeing results in salvage line therapy that we were frankly better than we expected and better than second line. And even though it was a small number of patients, we wanted to reach out directly to the FDA to see if we couldn't have an accelerated path for this drug. You know, the normal path of approval is you complete a phase 12 study, you run all the reports, you have an end of phase meeting with FDA.

當然。所以我不會說我們在任何方面都不一致。不，我只是說我們正在參與討論。我想，我們所看到的，我們在今年早些時候的電話會議上說過，當我們開始獲得這些患者的第一份數據時，我們看到我們看到了挽救線治療的結果坦率地說，我們比我們預期的要好，比第二線好。儘管患者數量很少，我們還是想直接與 FDA 聯繫，看看我們是否無法為這種藥物提供加速路徑。您知道，批准的正常途徑是您完成 12 期研究，運行所有報告，並與 FDA 舉行階段結束會議。

And then talk with the FDA about the what the registrational design looks like. We thought that given there's such a critical unmet need, no drugs are approved for this. And the salvage line data that we're getting look frankly terrific that, that we might have a faster path. So that's the discussion we're having right now of, can we have an accelerated approval path? And if so what does that look like? My hope is that, you know, what those discussions are, are in my view, hopefully going to be in a position where we'll have some clarity in Q1. But we will remain to be seen. I think at this point, we're just excited by the data and we're pleased that the FDA is engaged with us on identifying an accelerated or at least a faster path.

然後與 FDA 討論註冊設計的情況。我們認為，鑑於存在如此重要的未滿足需求，因此沒有藥物被批准用於此目的。我們得到的打撈線數據坦率地說看起來很棒，我們可能有一條更快的路徑。這就是我們現在正在討論的，我們能否有一個加速的批准路徑？如果是的話，那是什麼樣子的？我希望，你知道，在我看來，這些討論是什麼，希望我們能夠在第一季得到一些澄清。但我們還有待觀察。我認為在這一點上，我們只是對這些數據感到興奮，我們很高興 FDA 與我們合作確定一條加速或至少更快的路徑。

Great. Thanks Tim and the answer, maybe a question for you. You know, GA general administrative costs were down about a million dollars quarter over quarter and R&D was down about a half a million. As, you know, you continue to advance in the clinic. How should we be thinking of expenses going forward? You know, not only for the fourth quarter, but how should we be thinking of the cadence of expenses in 2025? I know it might be difficult as you're waiting for FDA guidance, but just wanted to get your initial thoughts on it.

偉大的。謝謝蒂姆和答案，也許是你的問題。您知道，GA 一般管理成本季減了約 100 萬美元，研發成本下降了約 50 萬美元。如您所知，您在診所中不斷進步。我們該如何考慮未來的開支？你知道，不僅是第四季度，我們該如何考慮 2025 年的支出節奏？我知道這可能很困難，因為您正在等待 FDA 的指導，但只是想了解您對此的初步想法。

Yes, thanks. Ed for the question. So, you know, our historical burn has really been in the call it $10million to $12 million range. We did some cost modulation earlier in the year that has brought that burn down. But I would expect that the normal burn for Curis in 2025 should probably stay around that $10 million that 10 million mark. It will, it will vary due to some timing of manufacturing. But for the most part, I would sort of assume that sort of $10 million number.

是的，謝謝。埃德的問題。所以，你知道，我們的歷史燒錢實際上是在 1000 萬至 1200 萬美元的範圍內。我們在今年早些時候進行了一些成本調整，從而減少了這種消耗。但我預計 2025 年 Curis 的正常消耗可能會維持在 1000 萬美元左右。會的，會因某些製造時間而有所不同。但在大多數情況下，我會假設這個數字是 1000 萬美元。

Okay, great. Thanks for taking my questions.

好的，太好了。感謝您回答我的問題。

Thanks, Ed.

謝謝，艾德。

Your next question comes from the line of [Bill Jahangiri from Priest Sec Securities]. Your line is now open. Please ask your question.

你的下一個問題來自於[Priest Sec Securities 的 Bill Jahangiri]。您的線路現已開通。請提出你的問題。

Good morning.

早安.

We had a question about Emma's potential in HR MDS given the abstract that was posted at ash. There's impressive responses and spices of mutants which isn't surprising at this point given the data you all have shown, but I, what we want to know what the broader potential is Given the specific impacts on gene signatures that you've seen. Like how representative are mutations in the MDS patient population? Is it 10% 15% or more? And given that Verona hasn't read out is pursuing a doublet without V and Hr MDs makes sense. Our HMA and MMOA or additive enough for that.

鑑於 ash 上發布的摘要，我們對 Emma 在 HR MDS 方面的潛力有疑問。考慮到你們所展示的數據，突變體的反應和香料令人印象深刻，這並不奇怪，但考慮到你們所看到的對基因特徵的具體影響，我們想知道更廣泛的潛力是什麼。例如 MDS 患者群體中的突變有多大代表性？是10%、15%還是更多？鑑於維羅納還沒有宣布追求沒有 V 和 Hr MD 的雙打是有道理的。我們的 HMA 和 MMOA 或添加劑足以滿足此要求。

Yeah. Hi. Bill. Thanks for calling in. Great question. So first, yeah, MPS is one of these things that not enough people are paying attention to. It's really exciting. And we're really looking forward to it as, you know, it's a challenging population. And until Verona reads out as a is standard of care, but, you know, once, once patients go through that, there's really nothing for those patients. So the opportunity is really terrific. So as you know, we've seen a lot of, we've seen a lot of responses more marrow CRS than CRS. We're seeing activity in patients with foot three mutation, patients with splicing mutations. And at this point, we're exploring the possibilities of different dosing regimens and also perhaps combining m of assertive with other agents. As you say, the, the Verona readouts going to matter, a lot of what that combination looks like. But I would say this is an evolving discussion. We're really looking forward to the data update that Doctor Garcia Manros going to provide at ash. And and hopefully it should be a really exciting discussion going into 2025. But yeah, thank you for paying attention to MDS. Not as many people see that as we do.

是的。你好。帳單。感謝您的來電。很好的問題。首先，是的，MPS 是沒有足夠多的人關注的事情之一。這真的很令人興奮。我們真的很期待它，因為你知道，這是一個充滿挑戰的人群。直到維羅納宣布這是護理標準，但是，你知道，一旦患者經歷了這種情況，這些患者就真的什麼都沒有了。所以這個機會實在是太棒了。如你所知，我們已經看到了很多，我們看到了很多關於 CRS 的反應，而不是 CRS。我們在患有足三突變、具有剪接突變的患者中看到了活性。目前，我們正在探索不同劑量方案的可能性，也可能將自信與其他藥物結合。正如你所說，維羅納的讀數很重要，很多組合看起來是什麼樣子。但我想說這是一個不斷發展的討論。我們非常期待加西亞·曼羅斯博士在灰燼中提供的數據更新。希望 2025 年這會是一次非常令人興奮的討論。但是，是的，感謝您關注 MDS。不像我們那麼多人看到這一點。

Thank you.

謝謝。

Your next question comes from the line of Li Watsek of Cantor Fitzgerald. Your line is now open. Please ask your question.

你的下一個問題來自康托·菲茨杰拉德（Cantor Fitzgerald）的李·瓦塞克（Li Watsek）。您的線路現已開通。請提出你的問題。

Hi team. This is Daniel Bronder on fully.

大家好。這是丹尼爾布朗德的完整報導。

We have a question regarding the PCNSL trial and the contribution of parts. Do you think that the FDA might raise that as a question? And also, do you have any historical data on to BTK responses that could help you answer that question?

我們對 PCNSL 試驗和零件貢獻有疑問。您認為 FDA 可能會提出這個問題嗎？另外，您是否有任何有關 BTK 回覆的歷史數據可以幫助您回答這個問題？

Sure. Thank you for the question. Thanks for the call. Yeah, I let me address the first question first and then I'll go to the second one. So the short answer is you know, discussions with FDA are evolving. So we'll have to see how they respond to that. But the design of the study is really meant to address that question implicitly.

當然。謝謝你的提問。感謝您的來電。是的，我請我先解決第一個問題，然後再討論第二個問題。所以簡短的回答是，您知道，與 FDA 的討論正在不斷發展。所以我們必須看看他們對此有何反應。但這項研究的設計其實是為了含蓄地解決這個問題。

So we're taking patients in immediately after they have progressed on BTK.

因此，在 BTK 治療取得進展後，我們會立即收治患者。

So the logic would be if you just progressed on a BTK inhibitor, retreating with that same inhibitor should have no effect, should have a zero response rate, you just progressed.

所以邏輯是，如果你剛剛在 BTK 抑制劑上取得了進展，那麼用相同的抑制劑進行撤退應該沒有效果，應該有零反應率，你剛剛取得了進展。

So by definition or by design, maybe more accurately, the benefit that you receive is much more likely to be due to the addition of M of assertive either in its monotherapy capacity or its synergistic effect, which we believe is at least the thesis suggests is powerful with the BTK inhibitor. So the first question is yes, the FDA we know is likely to have that question and we'll have that conversation with them and, and see how that play into the registrational design at the same time we're benefiting from the design of the study that's currently in progress, which, which does by definition or by design highlight the comparative effect of the two agents. And the second question or second part of the question you asked was about BTK and their efficacy. There's a lot of literature out there that the largest clinical study to date that was published was Kaan's study of Iru in PCNSL. And you may remember in that study in second line patients naive to BTK were able to get a 19%CR rate and a 52% Orr.

因此，根據定義或設計，也許更準確地說，您獲得的好處更有可能是由於添加了 M 的自信，無論是其單一治療能力還是其協同作用，我們認為至少論文表明是與BTK 抑製劑一起發揮作用。所以第一個問題是肯定的，我們知道 FDA 可能會提出這個問題，我們將與他們進行對話，看看這如何影響註冊設計，同時我們從註冊設計中受益目前正在進行的研究，根據定義或設計，確實強調了兩種藥物的比較效果。您提出的第二個問題或問題的第二部分是關於 BTK 及其功效。有許多文獻表明，迄今為止發表的最大的臨床研究是 Kaan 對 Iru 在 PCNSL 中的研究。您可能還記得，在那項研究中，未接受過 BTK 的二線患者能夠獲得 19% 的 CR 率和 52% 的 Orr。

So I said earlier, we're, we're very encouraged that our salvage line data are outperforming that and they are, it's, it's early days to be fair, but we would not have expected that in any disease, a drug being studied in the salvage line setting would outperform second line. But I would say that's why we and why our clinicians are so excited about the possibility of this regimen.

所以我之前說過，我們對搶救線數據的表現感到非常鼓舞，公平地說，現在還為時過早，但我們不會期望在任何疾病中，正在研究的藥物在打撈線設置中將優於第二線。但我想說，這就是為什麼我們和我們的臨床醫生對這種療法的可能性如此興奮。

Okay. Thank you so much. And if I may ask a follow up or another question, we were just wondering how are you going to go about the prioritization between your different programs? Your PCNSL program versus the AML & MDS program moving forward?

好的。太感謝了。如果我可以問一個後續問題或其他問題，我們只是想知道您將如何確定不同計劃之間的優先順序？您的 PCNSL 計劃與 AML 和 MDS 計劃有何不同？

Yeah, that's a fantastic question. So, I if I tell you about all the high class headaches, we have a curious, I am grateful that we are in the position that the drug works really where we would expect it to in a number of therapeutic areas. As you know, we're studying it in primary CNS lymphoma. We're studying it in AML. We're studying it in MDS. We've also got five it's going on in solid tumors that are reading out over the next 12 months. You know, we, we have this embarrassment of investment opportunities and embarrassment of riches. And maybe the hardest part of the job for the management team at Curis is trying to figure out how to prioritize those I would say at this point in time, because we're in discussions with FDA on primary CNS lymphoma and, and what that registrational path looks like, I think by definition, given the clear unmet need and the data that we're seeing that's got to be a very high priority for us. Coincidentally, it's a very attractive commercial market as well. Beyond that, expanding to the other five types of NHL where BTKS get used, that's a really compelling opportunity for us. AML & MDS, the data are about to read out at ash.

是的，這是一個很棒的問題。因此，如果我告訴你所有高級頭痛的情況，我們會感到好奇，我很感激我們所處的位置，該藥物在許多治療領域確實發揮了我們所期望的作用。如您所知，我們正在研究原發性中樞神經系統淋巴瘤。我們正在 AML 中研究它。我們正在 MDS 中研究它。我們還得到了 5 個實體瘤中發生的情況，將在未來 12 個月內公佈。你知道我們我們有這個投資機會的尷尬和財富的尷尬。對於Curis 管理團隊來說，工作中最困難的部分可能是試圖弄清楚如何優先考慮我此時所說的這些內容，因為我們正在與FDA 就原發性中樞神經系統淋巴瘤進行討論，以及註冊的內容我認為根據定義，考慮到明確的未滿足需求和我們看到的數據，這條路徑看起來像我們的一個非常高的優先順序。巧合的是，這也是一個非常有吸引力的商業市場。除此之外，擴展到使用 BTKS 的其他五種 NHL，這對我們來說是一個非常有吸引力的機會。AML & MDS，資料即將在灰燼中讀出。

So I'd say with those data in hand, let's have that same discussion that we're having about NHL. What is the best path to approval and how do we engage the regulatory authorities in that discussion? And then shortly thereafter, we're going to start getting data in solid tumors It's a great question. Today, we're prioritizing primary C lymphoma, but it is absolutely a high cost headache for us. How to prioritize all of these opportunities?

所以我想說，有了這些數據，讓我們進行與 NHL 相同的討論。獲得批准的最佳途徑是什麼？此後不久，我們將開始取得實體瘤的數據，這是一個很好的問題。今天，我們優先考慮原發性 C 淋巴瘤，但這對我們來說絕對是一個高成本的頭痛問題。如何優先考慮所有這些機會？

Okay. Thank you so much for taking my question.

好的。非常感謝您回答我的問題。

Thank you.

謝謝。

Your next question comes from the line of Dane Leone of Raymond James. Your line is now open. Please ask your question.

你的下一個問題來自雷蒙德詹姆斯 (Raymond James) 的戴恩利昂 (Dane Leone)。您的線路現已開通。請提出你的問題。

Hi guys. Thanks for taking the questions a couple from me. First, can you walk us through the, your current assessment of what you'll need as far as the data package for primary CNS lymphoma in particular? What do you think will be the sufficient number of patients in the safety database at the go forward, combination with the brute nib and Emma? And how many patients have you currently treated at or above that dose of Emma? Do you think 100 patients is kind of the rough threshold kind of based on precedent? And then secondly, can you speak to some of the challenges you've seen in enrolling the triplet study? You know, whether that be disposition of the MRD positive CR AML patients or just in general issues with AA and then, and timing of the, the treatment of patients with those with those agents? Thanks.

嗨，大家好。感謝您回答我的幾個問題。首先，您能否向我們介紹一下您目前對原發性中樞神經系統淋巴瘤資料包所需內容的評估？您認為，與粗暴筆尖和艾瑪結合，安全資料庫中的患者數量將達到多少？您目前以或高於該劑量的艾瑪治療了多少患者？您認為 100 名患者是否是基於先例的粗略閾值？其次，您能談談您在參加三胞胎研究時遇到的一些挑戰嗎？您知道，這是否是 MRD 陽性 CR AML 患者的處置，還是只是 AA 的一般問題，然後以及使用這些藥物治療患者的時間安排？謝謝。

All right. Thank you Dane. So great questions. Let me start with the primary CNS lymphoma question and then I'll go to the, the triplet study. So the primary CNS lymphoma study. To be Honest, we, that's the whole point of the discussion we're having with FDA. As you know, the normal process for any drug going through studies is you run a phase one to do dose escalation. When you get those data back, follow the patients lock the database, produce all the reports. Go to the FDA, have an end to face meeting, talk about the registrational design and then you go into pivotal I think given the data we have we thought it it should be it was worth having a conversation with the FDA to see if they'd be interested in running a faster process. We're grateful that they agreed to take that call. We're now in discussions in primary CNS lymphoma. There's not a lot of precedent, but we do know that there, there are two studies ongoing right now with a BTK inhibitor. So Ibrutinib is the one that today is the standard of care for BTK inhibitors. But Ono pharmaceuticals has a BTK inhibitor NIB, which is approved in Japan for primary CNS lymphoma and is now in its study to get approval in the US. We know that for that study, it's second line, not salvage. Obviously, they're trying to displace a brut nib and they also have a frontline study that they're using Truab in combination with methotrexate based regimens.

好的。謝謝丹恩。這麼好的問題。讓我從原發性中樞神經系統淋巴瘤問題開始，然後我將討論三聯體研究。所以對原發性中樞神經系統淋巴瘤進行研究。老實說，這就是我們與 FDA 討論的重點。如您所知，任何藥物進行研究的正常過程都是進行第一階段以進行劑量遞增。當你取回這些數據時，追蹤患者鎖定資料庫，產生所有報告。去 FDA，舉行一次面對面的會議，討論註冊設計，然後進入關鍵階段，我認為鑑於我們擁有的數據，我們認為應該與 FDA 進行對話，看看他們是否「 d 對運行更快的進程感興趣。我們很感激他們同意接聽電話。我們現在正在討論原發性中樞神經系統淋巴瘤。雖然沒有很多先例，但我們確實知道目前正在進行兩項關於 BTK 抑制劑的研究。因此，依魯替尼是當今 BTK 抑制劑的標準治療藥物。但小野製藥有一種 BTK 抑制劑 NIB，該藥物在日本已被批准用於原發性中樞神經系統淋巴瘤，目前正在研究以在美國獲得批准。我們知道，對這項研究來說，這是二線治療，而不是挽救治療。顯然，他們正在嘗試取代原味筆尖，並且他們還進行了一項前沿研究，表明他們正在將 Truab 與基於甲氨蝶呤的治療方案結合使用。

In their study the frontline study was of 75 or is n of 75. The second line study is a of 45 presumably salvage line setting wouldn't need 45.

在他們的研究中，第一線研究為 75 人或 n 為 75 人。第二線研究是 45 個，大概搶救線設定不需要 45 個。

Now, the question there is, of course, given our data from an efficacy perspective, that might make sense. But we need to recognize that, you know, Truab has a larger safety database simply because it's already approved in Japan.

當然，現在的問題是，從功效角度考慮我們的數據，這可能是有道理的。但我們需要認識到，Truab 擁有更大的安全資料庫，只是因為它已經在日本獲得批准。

So I don't exactly know where the FDA is going to come out, but we think it's reasonable suggest that if they're okay with granting us accelerated approval, that that's a smaller study and that then we would have a larger study with perhaps a survival based endpoint in a confirmatory trial. All of that's conjecture at this point, we, we need to finish these discussions and see how the FDA feels about that. But I think given the precedent that Ono has in their study sizes, it makes sense that in this ultra rare indication, a small study would be appropriate. It's one of the reasons of course, that we chose primary C Symp Forma.

所以我不知道 FDA 會在哪裡得出結論，但我們認為這是合理的建議，如果他們同意加速批准我們，那是一項較小的研究，然後我們可能會進行一項更大規模的研究驗證性試驗中基於生存的終點。目前所有這些都只是猜測，我們需要完成這些討論，看看 FDA 對此有何看法。但我認為，鑑於小野在研究規模方面的先例，在這種極其罕見的適應症中，進行一項小型研究是合適的，這是有道理的。這當然是我們選擇初級 C Symp Forma 的原因之一。

Now, on the triplet study, you, you had asked specifically about the design. What question were you looking to have about the design?

現在，在三聯體研究中，您，您專門詢問了設計。您對設計有什麼疑問？

MRD to some of the, yeah, some, just some of the, the challenges you see in terms of enrollment and, and you know, getting patients progressed on that study, you know, whether that's just the disposition of the MRD, positive CRML patients or it's more an issue kind of getting patients who are, have, are receiving or received AB in the front line and are receiving it in the maintenance setting. Any reticence you've seen from docs in terms of adding additional agent to an event in that setting and insight on your strategy moving forward to kind of boost enrollment there.

MRD 對一些，是的，一些，只是一些，你在入組方面看到的挑戰，你知道，讓患者在這項研究中取得進展，你知道，這是否只是 MRD 的處置，積極的 CRML患者，或者更重要的是讓那些正在前線接受AB治療的患者以及在維持環境中接受AB治療的患者。您從文件中看到的關於在該設定中向活動中添加額外代理的任何沉默，以及對您的策略的洞察力，以提高那裡的註冊人數。

Yeah. No, I think you put your finger on it. It's not a reticence at all or a safety issue at all. It's just how do you find patients who are on a, even for NCR and still, I am already positive and stable enough that they can go into, you know, into our study into the triplet, you know, at this point in time, what we really want to try and do is accentuate the safety. We, the long term solution to finding all the patients is of course, go from cycle one day one to get the patients the minute they're diagnosed and go to a lot of sites.

是的。不，我想你已經把手指放在上面了。這根本不是沉默或安全問題。這只是你如何找到接受 NCR 治療的患者，而且我已經足夠積極和穩定，他們可以進入，你知道，進入我們對三胞胎的研究，你知道，在這個時間點，我們真正想要嘗試做的是強調安全性。當然，找到所有患者的長期解決方案是，我們從第一天的一個週期開始，在患者被診斷出來的那一刻就找到他們，並前往許多地點。

We're at a very small number of sites we're simply looking to, to make sure that this patient that this combination of Emma Asa and then is going to be safe and tolerable as you know, Asa and then are a little tricky, you know, no two sites dose them the same way. Anecdotally. Half of all patients who go on a even at some point have to come off for tolerability, not just efficacy. We want to make sure that, you know, the, the MAN combination is tolerable first. So that's why we're going after these patients. So it won't take long. We just need a handful of patients and we just want to follow them to make sure we understand it. Once we do, then we, then we frankly turbocharge the study, we go to cycle one day one, we expand the number of sites and at that point once it's been shown to be safe and tolerable. No, I think the you'll find the physician community is very eager to find something that will increase the potency of that a regimen.

我們只是在極少數的地點尋找，以確保這位患者使用艾瑪·阿薩（Emma Asa）和然後的這種組合將是安全和可耐受的，如你所知，阿薩（Asa）和然後是有點棘手，你知道，沒有兩個網站以相同的方式使用它們。有趣的是。一半的患者在某些時候必須停止使用甚至是為了耐受性，而不僅僅是療效。我們首先要確保 MAN 組合是可以忍受的。這就是我們要追蹤這些患者的原因。所以不會花很久。我們只需要少數患者，我們只想追蹤他們以確保我們理解它。一旦我們這樣做了，然後我們坦率地加強了研究，我們一天一開始循環，我們擴大站點的數量，然後一旦它被證明是安全和可以忍受的。不，我想你會發現醫生界非常渴望找到能增加該療法效力的東西。

Got it. Thank you.

知道了。謝謝。

Thank you. Thanks for your call.

謝謝。感謝您的來電。

We do not have further questions at this time, James Dentzer. Please continue.

詹姆斯·丹澤，我們目前沒有其他問題。請繼續。

Thank you and thank you everyone for joining us on today's call.

謝謝大家參加今天的電話會議。

And as always a special, 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, especially at origin in the NCI and the academic community for their ongoing collaboration and support. We look forward to updating you again soon.

一如既往，特別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，感謝我們的合作夥伴，特別是來自 NCI 的合作夥伴和學術界的持續合作和支持。我們期待盡快再次為您提供最新消息。

Operator.

操作員。

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。