Curis Inc (CRIS) 2024 Q2 法說會逐字稿

Good morning, ladies and gentlemen. And welcome to the Curis provide second-quarter 2024 Business Update Conference Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. (Operator Instructions)

早安，女士們先生們。歡迎參加 Curis 提供的 2024 年第二季業務更新電話會議。此時，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。（操作員說明）

This call is being recorded on Thursday, August 1, 2024. I would now like to turn the conference over to Diantha Duvall. Please go ahead.

此電話錄音於 2024 年 8 月 1 日星期四進行。我現在想把會議交給黛安莎·杜瓦爾。請繼續。

Thank you and welcome to Curis second quarter 2024 business update call. Before we begin, I would like to encourage everyone to go to the Investor section of our website at www.curis.com to find our second quarter 2024 business update press release and related financial tables.

感謝您並歡迎參加 Curis 2024 年第二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 2024 年第二季業務更新新聞稿和相關財務表格。

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 the call. I'd now like to turn the call over to 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。我們還將在通話結束時提供問答時間。我現在想把電話轉給吉姆。

Thank you, Diantha. Good morning, everyone, and welcome to Curis second quarter business update call. Let's start with our TakeAim Lymphoma study, which is evaluating emavusertib in combination with ibrutinib in relapsed/refractory PCNSL patients that have failed after treatment with a BTK inhibitor. These patients have generally seen methotrexate chemo and radiation in the front-line setting, followed by ibrutinib in the second line.

謝謝你，黛安莎。大家早上好，歡迎致電 Curis 第二季業務更新。讓我們從 TakeAim 淋巴瘤的研究開始，該研究正在評估 emavusertib 與 ibrutinib 聯合用於治療 BTK 抑制劑治療失敗的複發/難治性 PCNSL 患者。這些患者通常在一線接受甲胺蝶呤化療和放療，然後在二線接受依魯替尼治療。

As patients progress on ibrutinib, they're eligible to enroll into our study where we add emavusertib to their ibrutinib regimen. The scientific thesis for this combination is that blocking both of the pathways driving NHL, the TLR pathway with emavusertib and the BCR pathway with ibrutinib, can enable patients to achieve an objective response even after they have progressed on ibrutinib in monotherapy.

隨著患者在依魯替尼治療中取得進展，他們就有資格參加我們的研究，我們將 emavusertib 加入他們的依魯替尼治療方案中。這種組合的科學論點是，阻斷驅動 NHL 的兩條途徑，即用 emavusertib 阻斷 TLR 途徑和用 ibrutinib 阻斷 BCR 途徑，可以使患者即使在接受 ibrutinib 單一療法取得進展後也能獲得客觀緩解。

We presented data for the first five patients in this study at the ASH conference last December, where we reported an objective response rate over 50%. These data were early but very encouraging, especially given the high unmet need in this population.

我們在去年 12 月的 ASH 會議上展示了本研究中前 5 名患者的數據，當時我們報告了超過 50% 的客觀緩解率。這些數據雖為早期數據，但非常令人鼓舞，特別是考慮到該族群的需求未得到滿足。

We've continued to enroll patients in this study, and as we noted in our press release this morning, have recently initiated discussions with regulatory authorities to gain alignment on the registrational path for emavusertib in combination with ibrutinib in primary CNSL.

我們繼續招募患者參與這項研究，正如我們在今天早上的新聞稿中指出的那樣，我們最近開始與監管機構進行討論，以就 emavusertib 與 ibrutinib 聯合用於原發性 CNSL 的註冊路徑達成一致。

It goes without saying that defining the registrational path is a critical next step in emavusertib's development, and I'm pleased with our most recent engagement with FDA. I look forward to communicating the outcome of these discussions at the appropriate time.

不用說，定義註冊路徑是 emavusertib 開發的關鍵下一步，我對我們最近與 FDA 的合作感到高興。我期待在適當的時候傳達這些討論的結果。

Discussions are also progressing in Europe, where we're pleased to report that emavusertib has been granted orphan drug designation for primary CNS lymphoma by the European Commission. This designation provides several benefits, including 10 years of market exclusivity, reduced fees for protocol and scientific assistance, as well as marketing authorization applications, and a central application process for marketing authorization with the European Medicines Agency.

歐洲的討論也正在取得進展，我們很高興地報告，emavusertib 已被歐盟委員會授予治療原發性中樞神經系統淋巴瘤的孤兒藥資格。此頭銜具有多項優勢，包括 10 年市場獨佔權、降低方案和科學援助費用、行銷授權申請以及歐洲藥品管理局行銷授權的中央申請流程。

While these regulatory discussions are ongoing, we continue to make excellent progress on the operational front as well, and expect to reach our target number of 30 clinical sites in the US and Europe, and have initial data for 15 to 20 patients by year end.

雖然這些監管討論仍在進行中，但我們在營運方面也繼續取得了巨大進展，預計將在美國和歐洲達到 30 個臨床中心的目標數量，並在年底前獲得 15 至 20 名患者的初步數據。

Now let's move to our TakeAim Leukemia study, which is evaluating emavusertib in monotherapy in patients with relapsed/refractory AML. At ASCO and EHA earlier this year, we provided updated data for two patient populations in this study, patients with a splicing factor mutation and patients with a FLT3 mutation.

現在讓我們進入 TakeAim 白血病研究，該研究正在評估 emavusertib 單藥治療復發/難治性 AML 患者的效果。今年早些時候，我們在 ASCO 和 EHA 上提供了本研究中兩個患者群體的最新數據，即具有剪接因子突變的患者和具有 FLT3 突變的患者。

In the splicing factor mutation, 4 of 18 evaluable patients achieved an objective response, including one complete remission or CR, two CRs with partial hematologic recovery, or CRh, and one morphologic leukemia-free state or MLFS. In the FLT3 population, 6 of 11 evaluable patients achieved an objective response, including three CRs, one CRh, and two MLFSs.

在剪接因子突變方面，18 名可評估患者中有 4 名獲得了客觀緩解，包括 1 名完全緩解或 CR，2 名 CR 且部分血液學恢復或 CRh，以及 1 名形態學無白血病狀態或 MLFS。在 FLT3 族群中，11 名可評估患者中有 6 名獲得客觀緩解，包括 3 名 CR、1 名 CRh 和 2 名 MLFS。

Also of note, three of the patients were naïve to treatment with a FLT3 inhibitor. All three of these patients achieved objective responses, and three of the remaining eight patients, those who had failed prior treatment with a FLT3 inhibitor, were able to achieve an objective response with emavusertib. We believe these data support emavusertib's novel mechanism and its potential as a treatment for patients with relapsed/refractory AML.

另外值得注意的是，其中三名患者從未接受過 FLT3 抑制劑治療。所有三名患者均獲得了客觀緩解，其餘 8 名患者中的 3 名（先前使用 FLT3 抑制劑治療失敗的患者）能夠透過 emavusertib 獲得客觀緩解。我們相信這些數據支持 emavusertib 的新穎機制及其作為治療復發/難治性 AML 患者的潛力。

In the frontline setting, you may remember that preclinical data demonstrate a synergistic effect when emavusertib is combined with azacitidine and venetoclax, the standard-of-care in frontline AML. We recently initiated a study of this triple combination, that is emavusertib in combination with azacitidine and venetoclax in frontline AML. We expect to have initial safety data from this study later this year.

在一線環境中，您可能還記得，臨床前數據表明，當 emavusertib 與阿扎胞苷和維奈托克（一線 AML 的護理標準）聯合使用時會產生協同效應。我們最近啟動了一項關於這種三重療法的研究，即 emavusertib 與阿扎胞苷和維奈托克聯合用於一線 AML。我們預計今年稍後將獲得這項研究的初步安全數據。

Overall, I'm very pleased with the progress in both our TakeAim Leukemia and TakeAim Lymphoma studies, and I look forward to providing additional updates as the year progresses.

總的來說，我對 TakeAim 白血病和 TakeAim 淋巴瘤研究的進展感到非常滿意，我期待著隨著時間的推移提供更多更新。

With that, I'll turn the call over to Diantha for the financial update.

這樣，我會將電話轉給 Diantha，以了解最新的財務狀況。

Thank you, Jim. Curis reported a net loss of $11.8 million or $2.03 per share, as compared to a net loss of $12 million or $2.47 per share, for the same period in 2023. Curis reported a net loss of $23.7 million or $4.08 per share for the six-month ended June 30, 2024, as compared to a net loss of $23.5 million or $4.87 per share for the same in 2023.

謝謝你，吉姆。Curis 報告淨虧損 1,180 萬美元，即每股 2.03 美元，而 2023 年同期淨虧損為 1,200 萬美元，即每股 2.47 美元。Curis 報告稱，截至 2024 年 6 月 30 日的六個月淨虧損為 2,370 萬美元，即每股 4.08 美元，而 2023 年同期淨虧損為 2,350 萬美元，即每股 4.87 美元。

Research and development expenses were $10.3 million for the second quarter of 2024, as compared to $10 million for the same period in 2023. Research and development expenses were $19.9 million for the six-month ended June 30, 2024, as compared to $19.2 million for the same period in 2023.

2024 年第二季的研發費用為 1,030 萬美元，而 2023 年同期為 1,000 萬美元。截至2024年6月30日的六個月，研發費用為1,990萬美元，而2023年同期為1,920萬美元。

General and administrative expenses were $4.8 million for the second quarter of 2024, as compared to $4.2 million for the same period in 2023. General and administrative expenses were $9.7 million for the six-month ended June 30, 2024, as compared to $9 million for the same period in 2023. The increases in both research and development and general and administrative expenses are primarily attributable to higher employee-related costs.

2024 年第二季的一般及管理費用為 480 萬美元，而 2023 年同期為 420 萬美元。截至 2024 年 6 月 30 日的六個月，一般及行政費用為 970 萬美元，而 2023 年同期為 900 萬美元。研究與發展以及一般和管理費用的增加主要歸因於員工相關成本的增加。

Curis cash, cash equivalents and investments totaled $28.4 million, and there were approximately 5.9 million shares of common stock outstanding. We expect that our existing cash, cash equivalents and investments should enable us to maintain our planned operations into the first quarter of 2025.

Curis 現金、現金等價物和投資總額為 2,840 萬美元，已發行普通股約 590 萬股。我們預計，我們現有的現金、現金等價物和投資應該能夠使我們將計劃營運維持到 2025 年第一季。

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

至此，我想開始提問。操作員？

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions)

謝謝。女士們、先生們，我們現在開始問答環節。（操作員說明）

Yale Jen, Laidlaw.

耶魯詹，萊德勞。

Good morning and thanks for taking the question and congrats on all the progress. I've got two here. The first one is that in terms of the PCNSL readout toward the end of the year, what do you consider to be the bar for advancing the program forward? In other words, what would be the guidepost that you were looking for? Then I have a follow-up.

早安，感謝您提出問題並祝賀所有進展。我這裡有兩個。第一個是，就年底的 PCNSL 數據而言，您認為推進該計劃的標準是什麼？換句話說，您正在尋找的路標是什麼？然後我有一個後續行動。

So just as a reminder, Yale. Thank you, by the way, for calling in for the question. As a reminder, we're looking to treat patients who have failed the BTK inhibitor. So let's put this into perspective. They failed first-line treatment. They failed the BTK inhibitor.

謹此提醒一下，耶魯大學。順便說一句，謝謝您打電話提問。提醒一下，我們正在尋求治療 BTK 抑制劑失敗的患者。因此，讓我們正確看待這一點。他們的一線治療失敗了。他們的 BTK 抑制劑失敗了。

If we retreated them with the BTK inhibitor, which is really that same choice over again, of course, they wouldn't respond. What we're looking to see is if we can get objective responses, period.

如果我們用 BTK 抑制劑撤退它們，這實際上是同樣的選擇，當然，它們不會做出反應。我們希望看到的是我們是否能夠得到客觀的回應，就這樣。

Now, I realize the data have been a lot better than that so far, but I think the bar for patients is, can we show that the thesis holds, that even if you've failed on a BTK inhibitor, adding emavusertib to it fundamentally changes the efficacy of that regimen. That's what we're really looking for.

現在，我意識到數據比到目前為止要好得多，但我認為患者的標準是，我們能否證明論文成立，即使您在 BTK 抑製劑上失敗了，從根本上添加 emavusertib改變該方案的功效。這就是我們真正在尋找的。

Okay. And (multiple speakers) --

好的。和（多位發言者）——

And of course, in a larger number of patients, right? Of course.

當然，在更多的患者中，對嗎？當然。

Absolutely. And you anticipate about maybe at least 15 patients roughly at a time when you report the data?

絕對地。當您報告數據時，您預計一次大約至少有 15 名患者？

That's right.

這是正確的。

Okay. And maybe the follow-up question here is that in terms of the leukemia, congrats on all the data that the positive data reported earlier. And I believe you mentioned there's different options you can pursue going forward, obviously, depending on the data to be reported in the near future. Some of the options in terms of plus three, you could have either for the naïve patient or extremely experienced patients, or as well as for the [FFM], you would obviously have experienced the patients on that only. How would you consider different optionality or maybe you want to take it all heading to 2025?

好的。也許這裡的後續問題是，就白血病而言，祝賀先前報告的陽性數據的所有數據。我相信你提到過，顯然，你可以採取不同的選擇，這取決於不久的將來報告的數據。在加三方面的一些選項，您可以為新手患者或非常有經驗的患者提供，或者對於[FFM]，您顯然只會在這方面經歷過患者。您會如何考慮不同的選擇，或者也許您想在 2025 年之前全部採用？

Sure. So, as you know, in leukemia, there's more optionality and that's a fortunate consequence of the design of the molecule, right? Because the molecule hits IRAK4, which is expressed in nearly every --

當然。所以，如你所知，在白血病中，有更多的選擇，這是分子設計的幸運結果，對嗎？因為該分子會擊中 IRAK4，而 IRAK4 幾乎在所有細胞中都有表現。--

Hello? Hello.

你好？你好。

Ladies and gentlemen, I would like to inform you that the speaker has been disconnected. Please wait a while. Thank you.

女士們、先生們，我想通知你們，揚聲器已斷開。請稍等。謝謝。

Operator, this is Jonathan Zung from Curis. Jim is trying to dial back in.

接線員，我是 Curis 的 Jonathan Zung。吉姆正在嘗試撥回電話。

We're back in, Jonathan.

我們回來了，喬納森。

Okay.

好的。

Thank you very much.

非常感謝。

Not sure what happened. We got disconnected from the call. So I was answering Yale Jen's question. Yale, perhaps, you can help me with where I got cut off?

不知道發生了什麼事。我們的通話被掛斷了。所以我正在回答耶魯詹的問題。耶魯，也許你能幫我解決我被切斷的地方？

Sure. Not a problem. The second question is that for the leukemia, you have different options to contemplate in terms of whether for FLT3, you will treat targeting either the naïve treatment -- naïve or treatment-experienced, as well as for the FFM that you would treat, obviously, only the treatment-experienced. So among the three options -- I guess whether you want to, one, two or all?

當然。不是問題。第二個問題是，對於白血病，您有不同的選擇來考慮，對於 FLT3，您是否將針對初次治療（初次治療或有治療經驗）以及您選擇的 FFM 進行治療。經驗的人。那麼在這三個選項中——我猜你是否想要一個、兩個還是全部？

Yes. So a couple of thoughts. So let's first talk about frontline therapy, which would be combination and then separately monotherapy with FLT3, and then within FLT3, of course, breaking it out into the separate groups for naïve and for experienced.

是的。所以有幾個想法。因此，我們首先討論第一線治療，即聯合使用 FLT3，然後單獨進行單一治療，然後在 FLT3 內，當然，將其分為針對新手和有經驗的組別。

So as you know, one of the things that makes the molecule more attractive in the leukemia setting is that it hits IRAK4 and FLT3, IRAK4 being expressed in nearly all patients with AML, and then also FLT3, where the FLT3 mutation we know is present in roughly a third of the population.

如您所知，使該分子在白血病治療中更具吸引力的原因之一是它能夠靶向 IRAK4 和 FLT3，IRAK4 幾乎在所有 AML 患者中表達，然後還有 FLT3，我們知道其中存在 FLT3 突變大約三分之一的人口。

So because it has that unique targeting, we think it could have a monotherapy application in leukemia, as opposed to frontline, where we think it will be available to all comers in combination with azacitidine and venetoclax, and of course in non-Hodgkin's lymphoma when it combines with ibrutinib.

因此，由於它具有獨特的標靶性，我們認為它可以在白血病中作為單一療法應用，而不是一線治療，我們認為所有患者都可以將其與阿扎胞苷和維奈托克聯合使用，當然也可以用於非何杰金氏淋巴瘤，當它與依魯替尼結合。

In the FLT3 subpopulation, as we look at monotherapy, you're exactly right. It could be appropriate for both naïve patients and experienced patients. It would be ideal, of course, with infinite resources to chase after all of those populations.

在 FLT3 亞群中，當我們考慮單一療法時，您是完全正確的。它可能適合新手患者和有經驗的患者。當然，如果有無限的資源來追捕所有這些人口，那就太理想了。

I think one of the discussions we're going to have at year-end, as we report a more full reading of the data set at ASH, is of course, which of these populations are we going to prioritize for moving forward most aggressively. So, I would say stay tuned for that discussion, but all of those opportunities are in front of us.

我認為，當我們報告對 ASH 數據集進行更全面的解讀時，我們將在年底進行的討論之一當然是，我們將優先考慮哪些人群最積極地向前推進。因此，我想說，請繼續關注該討論，但所有這些機會都在我們面前。

Okay. Great. That's very helpful. And maybe just quickly make it one more, which is in terms of IRAK4 composing, what might be the highlight for the upcoming one in effect? Thanks.

好的。偉大的。這非常有幫助。也許很快就再做一首，就IRAK4的作曲而言，下一首實際上的亮點可能是什麼？謝謝。

Yes. I think the IRAK4 symposium, we're very pleased to be doing that again this year. As you know, the level of interest in IRAK4 as a whole has gone up in the academic community every year since we first started publishing about IRAK4's utility on oncology.

是的。我認為，我們很高興今年再次舉辦 IRAK4 研討會。如你所知，自從我們首次開始發表有關 IRAK4 在腫瘤學方面的實用性的文章以來，學術界對 IRAK4 整體的興趣逐年上升。

We've got, I think, a really great cross-section of people involved this year, looking at leukemia experts, lymphoma experts, and also highlighting work in solid tumors. So the clinical data that Curis has been focused on today, and in our public forums, is really in leukemia and lymphoma, because that's where our clinical data are.

我認為，今年我們有來自各個領域的人員參與其中，包括白血病專家、淋巴瘤專家，並且還重點介紹了實體瘤方面的工作。因此，Curis 今天以及在我們的公共論壇上關注的臨床數據實際上是白血病和淋巴瘤的臨床數據，因為這是我們的臨床數據。

But we've also got five ISTs ongoing in solid tumors, and there is a wealth of really interesting preclinical data, and several of them are initiating studies now into patients as well. So I expect in the months, quarters, and years to come, that's going to become an increasingly important and interesting part of the story.

但我們還有五個針對實體瘤的 IST 正在進行中，並且有大量非常有趣的臨床前數據，其中一些現在也正在啟動針對患者的研究。因此，我預計在未來的幾個月、幾個季度和幾年裡，這將成為故事中越來越重要和有趣的部分。

Okay. Great. That's very helpful and congrats on the progress. I look forward to ASH for more details.

好的。偉大的。這非常有幫助，祝賀取得的進展。我期待 ASH 了解更多詳細資訊。

Thank you very much.

非常感謝。

Ed White, H.C. Wainwright.

懷特，H.C.溫賴特。

Good morning. Thanks for taking my question. Jim, you mentioned when you were discussing TakeAim Lymphoma that you recently met with the FDA to discuss those registrational paths. Just wanted to know your thoughts on what your ideal regulatory path would be? Thanks.

早安.感謝您提出我的問題。Jim，您在討論 TakeAim 淋巴瘤時提到，您最近與 FDA 會面討論了這些註冊路徑。只是想知道您對理想的監管路徑的想法是什麼？謝謝。

Well, I think we would like to move as expeditiously as we can, of course. The typical path in drug development is to conclude your Phase I, II study and have an end-of-phase meeting, and then talk about with the FDA how do you design the pivotal study.

嗯，我想我們當然希望盡快採取行動。藥物開發的典型路徑是結束 I、II 期研究並召開階段結束會議，然後與 FDA 討論如何設計關鍵研究。

I think in this case, because the unmet need is so clear, obviously the data that we put out last December looked very compelling, and I think, we thought it was appropriate to initiate these discussions a little ahead of schedule, and we are grateful that the regulatory authorities were amenable to having those discussions.

我認為在這種情況下，因為未滿足的需求是如此明確，顯然我們去年 12 月發布的數據看起來非常引人注目，而且我認為，我們認為提前一點啟動這些討論是合適的，我們很感激監管機構願意進行這些討論。

So we're in the middle of them now, and of course I can't comment on ongoing discussions, but we would look forward to working with both FDA and EMA on the most expeditious path to get this drug available to patients who sorely need it.

所以我們現在正處於其中，當然我不能對正在進行的討論發表評論，但我們期待與 FDA 和 EMA 合作，以最快捷的方式將這種藥物提供給迫切需要的患者它。

Okay, Jim. Thanks for taking my questions.

好吧，吉姆。感謝您回答我的問題。

You bet. Thank you. Operator?

你打賭。謝謝。操作員？

Soumit Roy.

蘇米特·羅伊.

Hi. Good morning, Jim and everyone. Sorry, I was a little delayed and missed the first few minutes of your prepared remarks. Is the -- are you still pursuing the relapsed/refractory path for FLT3 or spliceosome with ema monotherapy going forward? Is that the FDA conversation about?

你好。早安，吉姆和大家。抱歉，我有點遲到了，錯過了您準備好的演講的前幾分鐘。您是否仍在繼續探索 FLT3 或剪接體與 ema 單一療法的復發/難治性治療路徑？這是 FDA 的談話嗎？

Yes. So there was a similar question from Yale, from Yale Jen of Laidlaw about that. Thank you, Soumit. So as you know, we've got opportunities in leukemia in both monotherapy and combination, and of course, the combination opportunity in NHL.

是的。耶魯大學雷德勞分校的耶魯‧詹 (Yale Jen) 也對此提出了類似的問題。謝謝你，蘇米特。如你所知，我們在白血病方面有單一療法和聯合療法的機會，當然還有 NHL 聯合療法的機會。

The NHL1 is probably in the foremost of people's minds because that appears to be the one that's farthest along. As I say, we're already in discussions with regulatory authorities on what that registrational design ought to be.

NHL1 可能是人們最先想到的，因為它似乎是歷史最悠久的。正如我所說，我們已經在與監管機構討論註冊設計的內容。

I think with EMA, FLT3 and spliceosome as monotherapy, those data look really interesting. We're going to have a readout of that data set of roughly 20 patients in each group by year end. And then, of course, the combination, which we would expect, if it does mirror what we saw in the lab, we would expect this could be a really interesting add to frontline, to current standard of care in that setting.

我認為將 EMA、FLT3 和剪接體作為單一療法，這些數據看起來非常有趣。到年底，我們將讀出每組約 20 名患者的資料集。然後，當然，我們期望的組合，如果它確實反映了我們在實驗室中看到的情況，我們期望這可能是對前線、對該環境中當前護理標準的一個非常有趣的補充。

I think for FLT3 and spliceosome, as we see those mature data, we'll have that conversation at that time when it comes out. And of course, the initial readout, even though it's just a safety readout, there are a lot of people interested in that as well. We're going to have a high fast headache in front of ourselves to prioritize which of these studies we focus on first and fastest, but hold that thought.

我認為對於 FLT3 和剪接體，當我們看到那些成熟的數據時，我們會在它出來的時候進行對話。當然，最初的讀數，儘管這只是一個安全讀數，但也有很多人對此感興趣。我們將會非常頭痛，要優先考慮哪些研究是我們首先關注的，也是最快的，但要堅持這個想法。

Okay. So is it fair to expect these FDA meetings would be held post-ASH, maybe first quarter of '25?

好的。那麼，預期這些 FDA 會議將在 ASH 之後舉行（也許是 25 年第一季）是否公平？

For NHL, the discussions are already in process. For FLT3, we would wait to see what the data looked like before we would reach out to FDA. I think in AML, the landscape is more crowded. In primary CNS lymphoma, as you know, there are no drugs approved. In the third-line setting, I realize our data are early, but it's showing the kind of results that there isn't a comparable result in that setting for these patients.

對於 NHL，討論已經在進行中。對於 FLT3，我們會先看看數據是什麼樣子，然後再聯絡 FDA。我認為在反洗錢領域，情況更加擁擠。如您所知，對於原發性中樞神經系統淋巴瘤，尚無核准的藥物。在三線環境中，我意識到我們的數據還處於早期階段，但它顯示的結果表明這些患者在該環境中沒有可比較的結果。

So I think given the clear unmet need and given the data that we've seen to-date, we think there's an opportunity to get a treatment to patients that appears to be in these early days, very promising. So we want to move on that as aggressively as we can. And as I said, we're grateful that the regulatory authorities agreed to pick up that discussion earlier than we would normally do it.

因此，我認為，鑑於明顯的未滿足需求以及我們迄今為止所看到的數據，我們認為有機會為早期的患者提供非常有希望的治療。因此，我們希望盡可能積極地推動這項進程。正如我所說，我們很高興監管機構同意比我們通常進行的討論更早進行討論。

Got it. By NHL, you mean the PCNS?

知道了。NHL 是指 PCNS 嗎？

Yes.

是的。

Okay.

好的。

Yes.

是的。

And are you seeing any specific, when you're approaching the physicians for the enrollment, are you seeing any specific comments, like are they reluctant or there is no other options for these patients, so it's an easy pitch to use ema in this setting?

當您聯繫醫生進行登記時，您是否看到任何特定的評論，例如他們是否不願意或這些患者沒有其他選擇，因此在這種情況下使用 ema 很容易？

No. Unfortunately for the patients, but fortunately for the study, I think the unmet need in this population is, well, frankly, it's horrible for those patients. There are no drugs approved. Frontline, as you know, it's really high-dose methotrexate, chemo, and whole brain radiation.

不。對患者來說不幸的是，但對於這項研究來說幸運的是，我認為這個人群中未得到滿足的需求，坦白說，這對這些患者來說是可怕的。尚無藥物核准。如您所知，前線實際上是高劑量甲氨蝶呤、化療和全腦放療。

Once they progress on that, they typically go on ibrutinib, and then after that, there really is nothing. We hope to be part of a solution for these patients that in bringing this new treatment, it looks as though early days, early data, but it has the potential to be very promising.

一旦他們在這方面取得進展，他們通常會繼續服用依魯替尼，然後就真的什麼都沒有了。我們希望成為這些患者解決方案的一部分，這種新療法看起來還處於早期階段，早期數據，但它有潛力非常有前途。

And so as I say, we continue to enroll. We have a lot of enthusiasm among the community. I know when you went to the conference, you were able to catch up with several of the investigators yourself. Enthusiasm is really quite high. Early days, we know. I always want to be careful to mention that.

正如我所說，我們繼續招生。我們在社區中有很大的熱情。我知道當您參加會議時，您親自採訪了幾位調查人員。熱情確實相當高。早期，我們知道。我總是想小心地提及這一點。

But I have to say we're very excited by what we're seeing. Our physicians are very excited. And we're glad that the regulatory authorities were interested in entertaining the discussions a little ahead of schedule, which was, of course, very encouraging for us.

但我不得不說，我們對所看到的感到非常興奮。我們的醫生非常興奮。我們很高興監管機構有興趣提前一點討論，這當然對我們來說非常令人鼓舞。

Right. As we saw with Gilead's CAR-T also in PCNSL, it's a fairly high ICANS event. So small molecule on your safety profile certainly allows it. Another question, maybe a little bit aside from the blood cancer, in the solid tumor, do we have any visibility if the bladder cancer trial, when it will start recruiting, I don't know if this is an investigator-run trial with [KEYTRUDA] and emavusertib. Any thoughts would be appreciated.

正確的。正如我們在 PCNSL 中看到吉利德的 CAR-T 一樣，這是一個相當高的 ICANS 事件。因此，在安全性方面小分子肯定允許這樣做。另一個問題，也許除了血癌之外，在實體瘤中，如果膀胱癌試驗何時開始招募，我們是否有任何可見性，我不知道這是否是一項由研究者進行的試驗[ KEYTRUDA] 和emavusertib 。任何想法將不勝感激。

Sure. So as you know, we've got five investigator-sponsored trials going on right now in solid tumors. We've been focusing on the NHL study, and of course, the leukemia study, because those are the ones that are company-sponsored and those are the ones where we've got clinical data. But we've got studies going on in pancreatic and gastroesophageal, melanoma, urothelial bladder cancer and colorectal as well.

當然。如您所知，我們目前正在進行五項由研究者資助的實體腫瘤試驗。我們一直關注 NHL 研究，當然還有白血病研究，因為這些研究是公司贊助的，我們有臨床數據。但我們也正在胰臟癌、胃食道癌、黑色素瘤、膀胱尿路上皮癌和大腸癌進行研究。

All of those studies have really nice preclinical data that have been published at various conferences over the last 12 months to 24 months. And we're now at the point where they're moving into the clinic, which is really exciting. I hope we'll be in a position to see results from some of these studies in 2025.

所有這些研究都有非常好的臨床前數據，這些數據已在過去 12 個月到 24 個月的各種會議上發表。我們現在正處於他們進入診所的階段，這真的很令人興奮。我希望我們能夠在 2025 年看到其中一些研究的結果。

But again, these are ISTs. They're investigator-sponsored trials. They're not company-sponsored. So, of course, we don't actually have control over either the enrollment or the reporting of data from those studies. But we're watching them with great interest, and of course, very appreciative of the collaboration with each of these study sponsors.

但同樣，這些都是 IST。它們是研究者資助的試驗。他們不是公司贊助的。因此，當然，我們實際上無法控制這些研究的招募或數據報告。但我們非常感興趣地關注著他們，當然，非常感謝與每個研究贊助商的合作。

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。

Thank you very much.

非常感謝。

Li Watsek, Cantor.

李·瓦塞克，康托爾。

Good morning, guys. Sorry if I missed it earlier, but Jim, maybe just a digital question in terms of how you view the opportunity in lymphoma versus AML. It sounds like the unmet need there in lymphoma is a little bit higher and maybe less competitive. So, how are you thinking about maybe prioritize lymphoma versus AML? Are you waiting for some maybe regulatory input to make a decision?

早安，夥計們。抱歉，如果我之前錯過了，但 Jim，也許只是一個數字問題，關於您如何看待淋巴瘤與 AML 的機會。聽起來淋巴瘤方面未滿足的需求有點高，而且競爭力可能較低。那麼，您如何考慮優先考慮淋巴瘤與 AML 呢？您是否正在等待一些可能的監管意見來做出決定？

Yes. Thank you, Li. Thanks for calling in. Thanks for the question. So, in NHL versus AML, there are a couple of ways to answer that question. Of course, I think the interest in NHL is partially because that's the most recent data and that's the one where we're in discussions, of course, with regulatory agencies.

是的。謝謝你，李。感謝您的來電。謝謝你的提問。因此，在 NHL 與 AML 中，有幾種方法可以回答這個問題。當然，我認為對 NHL 的興趣部分是因為這是最新的數據，也是我們正在與監管機構討論的數據。

Across the landscape of NHL, it's obviously a much larger market as well. So, BTK inhibitors in 2023 had revenue of $11 billion. It's a massive space that hasn't had any novel drugs enter into it, excuse me, in recent years.

縱觀 NHL 的格局，這顯然也是一個更大的市場。因此，2023 年 BTK 抑制劑的收入為 110 億美元。這是一個巨大的領域，近年來還沒有任何新藥進入。

And if our recent data hold, we, of course, would look to move very aggressively in primary CNS lymphoma. And then with those data in hand and those processes underway, we would go across NHL to all of those other indications. I think that's really building the excitement from investors and why we focus on that more.

如果我們最近的數據成立，我們當然會在原發性中樞神經系統淋巴瘤方面採取非常積極的行動。然後，有了這些數據和正在進行的流程，我們將跨越 NHL 來了解所有其他適應症。我認為這確實讓投資人感到興奮，也是我們更關注這一點的原因。

In leukemia, I think the excitement is, while it is a more competitive space, as you note, the molecule really seems to be fortuitously designed for an AML setting. I mean, it was obviously deliberately designed as an IRAK4 inhibitor, and as you know, we deliberately designed key oncology targets of interest. But because it hits IRAK4 and FIT3, it really has the ability to offer an unusual benefit, a unique and independent targeted benefit for patients in that setting.

在白血病方面，我認為令人興奮的是，雖然這是一個更具競爭性的領域，但正如您所指出的，該分子似乎確實是為 AML 設定而偶然設計的。我的意思是，它顯然是故意設計為 IRAK4 抑制劑，正如你所知，我們故意設計了感興趣的關鍵腫瘤學靶點。但因為它擊中了 IRAK4 和 FIT3，所以它確實有能力為該環境下的患者提供不尋常的益處、獨特且獨立的目標益處。

So, yes, I think the excitement on NHL is partially because of the advanced state of the data within the context of the unmet need and the regulatory progress. But AML also very, certainly very high on our radar screen.

所以，是的，我認為 NHL 令人興奮的部分原因是在未滿足的需求和監管進展的背景下數據的先進狀態。但反洗錢在我們的雷達螢幕上也非常非常重要。

Okay. And then -- yes, I appreciate the color. And then maybe a question on the frontline AML combo strategy. Just curious if there's a plan to maybe stratify by IRAK4 long discussion and maybe have a step plan built around that, as well as for all comers?

好的。然後——是的，我很欣賞這種顏色。然後可能是關於前線反洗錢組合策略的問題。只是好奇是否有一個計劃可以透過 IRAK4 的長期討論進行分層，並且可能有一個圍繞該計劃以及針對所有參與者的步驟計劃？

Yes. So, thank you. I think we're thinking in leukemia, as you note, or certainly as you're implying, that there is a separate strategy for monotherapy versus combination. So, with FLT3 as an additional target, I think that offers the ability, given that the drug targets both IRAK4 and FLT3, offers the potential for best-in-class therapy among the FLT3 inhibitors, which is a third of the population in AML.

是的。所以，謝謝你。我認為我們正在思考白血病，正如您所指出的，或者當然正如您所暗示的那樣，單一療法與聯合療法有單獨的策略。因此，考慮到該藥物同時靶向IRAK4 和FLT3，以FLT3 作為額外靶點，我認為這提供了一種能力，為FLT3 抑製劑提供了同類最佳治療的潛力，FLT3 抑製劑佔AML 患者的三分之一。

And again, I know you know this, but for the benefit of others on the call, the research that we're pointing to originally published with the [Melgar paper] showed that the reason why patients on a FLT3 inhibitor don't do better than you might expect on a FLT3 inhibitor is the escape path is IRAK4. It's specifically toll-like receptor path signaling through IRAK4.

再說一次，我知道你知道這一點，但為了電話中其他人的利益，我們指出的最初與 [Melgar 論文] 一起發表的研究表明，服用 FLT3 抑製劑的患者效果不佳的原因與您對FLT3 抑制劑的預期不同的是，逃逸路徑是IRAK4。它是透過 IRAK4 專門發出的 Toll 樣受體路徑訊號。

So, by blocking both FLT3 and IRAK4, we're blocking both the primary driver -- primary path of the disease and its escape path. And that really, in our view, even though the data are early, it explains why the data look to be better than other FLT3 inhibitors. So, monotherapy there, I think, is a really exciting alternative.

因此，透過阻斷 FLT3 和 IRAK4，我們阻斷了主要驅動因素——疾病的主要路徑及其逃逸路徑。事實上，在我們看來，即使數據還很早，它也解釋了為什麼這些數據看起來比其他 FLT3 抑制劑更好。因此，我認為單一療法是一個非常令人興奮的替代方案。

In frontline, we just started that study, so we need to see whether or not it'll pan out, but the preclinical data are clear. IRAK4 is expressed in nearly every patient with AML, all comers. And we know azacitidine and venetoclax, which is the current standard-of-care, don't hit it.

在一線，我們剛開始這項研究，所以我們需要看看它是否會成功，但臨床前數據是明確的。IRAK4 幾乎在所有 AML 患者中都有表現。我們知道阿扎胞苷和維奈托克是目前的標準治療方法，但不要使用。

So, the preclinical data showed that when you added emavusertib to standards-of-care, when you added ema to the aza-ven doublet, there was a significant increase in efficacy. Now, we hope to see that in patients, and we've just started that study, but stay tuned. I hope that helps.

因此，臨床前數據表明，當您將 emavusertib 添加到護理標準中時，當您將 ema 添加到 aza-ven doublet 中時，療效會顯著增加。現在，我們希望在患者身上看到這一點，我們剛開始這項研究，但請繼續關注。我希望這有幫助。

Thanks.

謝謝。

(Operator Instructions) There are no further questions at this time. I'd now like to turn the call back over to Jim. Please go ahead.

（操作員說明） 目前沒有其他問題。我現在想把電話轉回給吉姆。請繼續。

Thank you, Operator. 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, the NCI, and the academic community for their ongoing collaboration and support. We look forward to updating you again soon. Operator?

謝謝你，接線生。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 團隊的辛勤工作和奉獻，感謝我們在 Aurigene、NCI 和學術界的合作夥伴持續的合作和支持。我們期待盡快再次為您提供最新消息。操作員？

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.

女士們、先生們，今天的電話會議到此結束。我們感謝您的參與，並請您斷開線路。