Syros Pharmaceuticals Inc (SYRS) 2024 Q2 法說會逐字稿

Good morning, and welcome to Syros Pharmaceuticals Second Quarter 2024 financial results conference call. At this time, all participants are in listen only mode. This call is being webcast live on the Investors and Media section of Syros website at www.syros.com. Please be advised that today's call is being recorded. At this time, I would like to turn the call over to Karen Hunady, Director of Investor Relations and Corporate Communications at Syros.

早安，歡迎參加 Syros Pharmaceuticals 2024 年第二季財務業績電話會議。此時，所有參與者都處於僅聽模式。本次電話會議正在 Syros 網站 www.syros.com 的投資者和媒體部分進行網路直播。請注意，今天的通話正在錄音。現在，我想將電話轉給 Syros 投資者關係和企業傳播總監 Karen Hunady。

Please go ahead.

請繼續。

Thank you

謝謝

This morning, we issued a press release announcing our second quarter 2024 financial results. The full release is available on in the (technical difficulty) section of Syros' website at www.syros.com. We will begin the call with prepared remarks by Conley Chee, our Chief Executive Officer; Dr. David Roth, our Chief Medical Officer; and Jason Haas, our Chief Financial Officer, will then open the call for questions.

今天上午，我們發布新聞稿，宣布 2024 年第二季財務業績。完整版本可在 Syros 網站 www.syros.com 的（技術難度）部分取得。我們將以我們的執行長 Conley Chee 準備好的演講開始電話會議； David Roth 博士，我們的首席醫療官；然後我們的財務長 Jason Haas 將開始提問。

Kristin Stephens, our Chief Development Officer is also here on the call with us and will be available for Q&A.

我們的首席開發官克里斯汀史蒂芬斯 (Kristin Stephens) 也將與我們通話並接受問答。

Before we begin, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our Quarterly Report on Form 10-Q that we filed this morning, our annual report on Form 10-K that we filed earlier in the year and any other filings that we may make with the SEC in the future. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

在開始之前，我想提醒大家，我們在本次電話會議上發表的聲明將包括前瞻性聲明。由於各種風險、不確定性和其他因素，包括我們在10-Q 表季度報告的風險因素部分中列出的因素，實際事件或結果可能與任何前瞻性陳述中明示或暗示的事件或結果存在重大差異。任何前瞻性陳述僅代表我們截至今天的觀點，不應被視為代表我們在任何後續日期的觀點。我們特別聲明不承擔更新或修改任何前瞻性陳述的義務。

I would now like to turn the call over to Conley. Conley?

我現在想把電話轉給康利。康利？

Thanks, Karen, and thank you, everyone, for joining us this morning.

謝謝凱倫，也謝謝大家今天早上加入我們。

At Syros, our mission is to develop new standards of care for the frontline treatment of patients with hematologic malignancies. Throughout the first half of 2024, we have laid a solid foundation in preparation for our upcoming data readouts for tamibarotene in AML and higher-risk MDS patients with RARA gene overexpression in the third and fourth quarters, respectively.

在 Syros，我們的使命是為血液惡性腫瘤患者的第一線治療制定新的護理標準。在整個 2024 年上半年，我們已經為即將在第三季和第四季分別讀取 AML 和 RARA 基因過度表現的高風險 MDS 患者的他米巴羅汀資料讀數奠定了堅實的基礎。

As we approach these readouts, we're working diligently to prepare for our first NDA filing and launch. So that upon approval, we are positioned to deliver tamibarotene to the thousands of higher-risk MDS patients in need of better care. I am pleased with our continued progress in advancing our launch readiness activities and commercialization plans. As we've previously mentioned, we plan to deliver tamibarotene to patients in the U.S. through our own commercial efforts following approval.

當我們接近這些讀數時，我們正在努力準備我們的首次 NDA 申請和發布。因此，一旦獲得批准，我們就可以向數千名需要更好照護的高風險 MDS 患者提供他米巴羅汀。我對我們在推進發射準備活動和商業化計劃方面不斷取得的進展感到高興。正如我們之前提到的，我們計劃在獲得批准後透過我們自己的商業努力向美國患者提供他米巴羅汀。

And we are well positioned to execute on this opportunity, given the concentrated call points in hematology and our team's successful track record in bringing new medicines to patients in need. We believe the market opportunity for tamibarotene is significant. Both higher-risk MDS and unfit AML are challenging diseases to treat. There are very few potential frontline therapies in late-stage development, and there remains a significant unmet need in these two closely related diseases.

鑑於血液學領域的集中呼叫點以及我們團隊在為有需要的患者提供新藥物方面的成功記錄，我們處於有利的位置來執行這個機會。我們相信他米巴羅汀的市場機會很大。高風險 MDS 和不適合的 AML 都是難以治療的疾病。處於後期開發階段的潛在一線療法非常少，這兩種密切相關的疾病仍然存在顯著的未滿足的需求。

This creates a meaningful opportunity for our differentiated and biologically targeted approach with tamibarotene to potentially alter the current treatment paradigm and provide profound benefit to patients in need of new options. Syros is currently evaluating tamibarotene in genomically defined subsets of higher-risk MDS and AML patients whose disease is characterized by the overexpression of the RARA gene. This represents a significant portion of the patient population, as we believe approximately 50% of MDS and 30% of AML patients are positive for RARA overexpression.

這為我們使用他米巴羅汀的差異化和生物靶向方法創造了一個有意義的機會，有可能改變當前的治療模式，並為需要新選擇的患者提供深遠的益處。Syros 目前正在評估他米巴羅汀在基因組定義的高風險 MDS 和 AML 患者亞群中的作用，這些患者的疾病特徵是 RARA 基因過度表達。這代表了患者群體的很大一部分，因為我們相信大約 50% 的 MDS 和 30% 的 AML 患者的 RARA 過度表現呈陽性。

We believe both of these indications represent substantial market opportunities, which provides a potential for tamibarotene to address a significant unmet need. We look forward to an exciting second half of the year with additional Phase II AML data in September and pivotal Phase III MDS data by mid Q4 as we work to deliver better options for patients.

我們相信這兩個適應症都代表著巨大的市場機會，這為他米巴羅汀提供了解決重大未滿足需求的潛力。我們期待著令人興奮的下半年到來，我們將在9 月獲得更多的AML 2 期數據，並在第4 季中期獲得關鍵的III 期MDS 數據，因為我們致力於為患者提供更好的選擇。

With that, let me turn the call over to David to review our programs and our upcoming milestones in more detail. David?

接下來，讓我將電話轉給 David，以更詳細地審查我們的計劃和即將到來的里程碑。大衛？

Thank you, Conley. We were very encouraged by the advancement of tamibarotene, our oral selective RAR alpha agonist as a potential new standard of care for higher-risk MDS and AML patients. Across multiple trials to date, tamibarotene has demonstrated high complete response rates, rapid time to response, and a favorable tolerability profile. We believe tamibarotene offers competitive differentiation due to its biologically targeted approach and the ability to combine with other therapies used in the treatment of MDS and AML as hypomethylating agents like azacitidine and even venetoclax with no additional myelosuppression.

謝謝你，康利。我們對他米巴羅汀（我們的口服選擇性 RAR α 激動劑）作為高風險 MDS 和 AML 患者的潛在新護理標準的進展感到非常鼓舞。在迄今為止的多項試驗中，他米巴羅汀已表現出較高的完全緩解率、快速的緩解時間和良好的耐受性。我們相信，他米巴羅汀因其生物靶向方法以及與用於治療MDS 和AML 的其他療法（如阿扎胞苷甚至維奈托克）聯合使用的能力而具有競爭優勢，且無需額外的骨髓抑制。

We know that hematologists and oncologists are looking for novel, targeted, convenient and easy to administer medicines that can offer differentiated benefits to patients, and this is exactly what we believe we have with tamibarotene.

我們知道，血液學家和腫瘤學家正在尋找新穎、有針對性、方便且易於給藥的藥物，為患者提供差異化的益處，而這正是我們認為他米巴羅汀所具有的優勢。

First, I'll start with our study of tamibarotene in MDS, which we are evaluating in an ongoing Phase III SELECT-MDS-1 trial in newly diagnosed higher-risk MDS patients with RARA overexpression. SELECT-MDS-1 is a global, randomized, double-blind, placebo-controlled trial evaluating the combination of tamibarotene and azacitidine compared to placebo and azacitidine. The trial's primary efficacy endpoint is complete response in the first 190 enrolled patients, which, together with supporting durability data can potentially serve as the basis for accelerated approval or full approval.

首先，我將從他米巴羅汀治療 MDS 的研究開始，我們正在一項正在進行的 III 期 SELECT-MDS-1 試驗中對新診斷的 RARA 過度表達的高風險 MDS 患者進行評估。SELECT-MDS-1 是一項全球、隨機、雙盲、安慰劑對照試驗，評估他米巴羅汀和阿扎胞苷的組合與安慰劑和阿扎胞苷的比較。該試驗的主要療效終點是前 190 名入組患者的完全緩解，這與支持耐久性數據一起可以作為加速批准或完全批准的基礎。

CR is an important and clinically meaningful efficacy endpoint due to its association with overall survival. Hematologic improvement, which is included in the CR endpoint criteria is also associated with clinical benefit because MDS patients often have low peripheral blood counts. Therefore, hematologic improvement is expected to resolve MDS symptoms associated with low counts such as infections, bleeding and fatigue.

CR 是一個重要且具有臨床意義的療效終點，因為它與總存活期有關。CR 終點標準中包含的血液學改善也與臨床效益相關，因為 MDS 患者的周邊血球計數通常較低。因此，血液學的改善有望解決與低計數相關的 MDS 症狀，如感染、出血和疲勞。

Taken together, the short- and long-term clinical benefits associated with achieving a CR are clinically compelling and reinforce our confidence in the potential of our SELECT-MDS-1 clinical trial, including our plan to continue enrolling patients to support the key secondary endpoint of overall survival.

總而言之，與實現 CR 相關的短期和長期臨床益處在臨床上引人注目，增強了我們對 SELECT-MDS-1 臨床試驗潛力的信心，包括我們計劃繼續招募患者以支持關鍵的次要終點總體生存率。

In June, we hosted a webinar event with 3 distinguished medical experts in the field to discuss SELECT-MDS-1 and the opportunity for tamibarotene to transform the standard of care for newly diagnosed higher-risk MDS patients with RARA overexpression. In these discussions, the physicians, all with significant experience in treating higher-risk MDS patients emphasized the need for new and safe therapies that provide better outcomes for these patients.

6 月，我們與該領域的 3 位傑出醫學專家舉辦了一次網路研討會，討論 SELECT-MDS-1 以及他米巴羅汀改變新診斷的 RARA 過度表達高風險 MDS 患者護理標準的機會。在這些討論中，在治療高風險 MDS 患者方面擁有豐富經驗的醫生都強調需要新的安全療法，為這些患者提供更好的結果。

They also noted the importance of using endpoints to accelerate the development and approval of novel agents, and they highlighted CR as the measure correlated to long-term benefit and overall survival.

他們還指出了使用終點加速新藥開發和批准的重要性，並強調 CR 是與長期獲益和整體生存相關的衡量標準。

We look forward to reporting pivotal CR data from the first 190 patients in SELECT-MDS-1 later this year, which we are optimistic will build on the clinical observations we have seen to date in both higher-risk MDS and AML.

我們期待在今年稍後報告SELECT-MDS-1 首批190 名患者的關鍵CR 數據，我們樂觀地認為這些數據將建立在我們迄今為止在高風險MDS 和AML 中看到的臨床觀察結果的基礎上。

Now let's turn to our SELECT-AML-1 Phase II trial, which is evaluating tamibarotene in newly diagnosed unfit AML patients with RARA overexpression. As a reminder, the objective of this study is to evaluate the safety and efficacy of the triplet regimen of tamibarotene in combination with venetoclax and azacitidine compared to venetoclax and azacitidine alone in approximately 80 patients randomized 1:1.

現在讓我們來看看我們的 SELECT-AML-1 II 期試驗，該試驗正在評估他米巴羅汀對新診斷的不健康 RARA 過度表達 AML 患者的作用。提醒一下，本研究的目的是在約80 名按1:1 隨機分組的患者中，評估他米巴羅汀合併維奈托克和阿扎胞苷三聯療法與單獨使用維奈托克和阿扎胞苷的安全性和有效性。

In December of last year, we reported data on our initial prespecified analysis, which included 23 patients, 19 of whom were response evaluable. The data showed a 100% CR/CRi rate and a 78% CR rate in patients treated with the triplet combination of tamibarotene, venetoclax and azacitidine as compared to a 70% CR/CRi rate and a 30% CR rate in the patients treated with venetoclax and azacitidine alone. The time to response was rapid with all patients in the triplet arm responding by the end of cycle 1 compared with 60% in the doublet arm.

去年 12 月，我們報告了初步預設分析的數據，其中包括 23 名患者，其中 19 名患者的反應可評估。數據顯示，接受他米巴羅汀、維奈托克和阿扎胞苷三合療法治療的患者的CR/CRi 率為100%，CR 率為78%，而接受他米巴羅汀、維奈托克和阿扎胞苷三重療法治療的患者的CR/CRi 率為70%，CR 率為30%。三聯組中的所有患者在第 1 週期結束時均出現反應，而雙聯組中只有 60% 的患者出現反應時間很快。

Consistent with prior observations, tamibarotene in combination with ven/aza was well tolerated and no new safety signals or additive toxicities were identified. Importantly, there was no evidence of increased myelosuppression in the triplet arm compared to the doublet, which further underscores tamibarotene's potential in combination with standard of care.

與先前的觀察結果一致，他米巴羅汀與 ven/aza 聯合使用具有良好的耐受性，並且沒有發現新的安全訊號或附加毒性。重要的是，沒有證據表明三聯組與雙聯組相比骨髓抑制增加，這進一步強調了他米巴羅汀與標準護理相結合的潛力。

We're excited to report the additional SELECT-AML-1 data in September at the SOHO 2024 Annual Meeting. The data are expected to include clinical activity and tolerability data from a prespecified analysis of more than 40 unfit AML patients with RARA overexpression, and we look forward to sharing this update with you.

我們很高興在 9 月的 SOHO 2024 年會上報告額外的 SELECT-AML-1 數據。這些數據預計將包括對 40 多名患有 RARA 過度表達的不健康 AML 患者進行預先指定分析的臨床活動和耐受性數據，我們期待與您分享這項更新。

I would now like to turn the call over to Jason, our Chief Financial Officer, to review our second quarter financial results. Jason?

我現在想將電話轉給我們的財務長傑森，以審查我們第二季的財務業績。傑森？

Thank you, David. Now turning to our second quarter financial results. We did not recognize revenue in the second quarter of 2024 as compared to recognizing revenue of $2.8 million in the second quarter of 23. The decrease reflects last year's termination of Syros' collaboration agreement with Pfizer. R&D expenses were $22 million in the second quarter of 2024 as compared to $29.6 million in the second quarter of 2023. The decrease was primarily due to the reduction in external R&D consulting, contract manufacturing and a reduction in headcount and related expenses.

謝謝你，大衛。現在轉向我們第二季的財務業績。與 2023 年第二季確認收入 280 萬美元相比，我們沒有在 2024 年第二季確認收入。這一下降反映了去年 Syros 與輝瑞合作協議的終止。2024 年第二季的研發費用為 2,200 萬美元，而 2023 年第二季的研發費用為 2,960 萬美元。減少的主要原因是外部研發諮詢、合約製造的減少以及員工人數和相關費用的減少。

Our R&D expenditures are now principally focused on the advancement of tamibarotene. G&A expenses were $5.5 million in the second quarter 2024 as compared to $7.2 million in the second quarter of 2023. The decrease was primarily due to a reduction in headcount and related expenses, consulting and facilities expenses. We reported a net loss for the second quarter of 2024 or $23.3 million or $0.59 per share compared to a net loss of $36.3 million or $1.30 per share for the same period in 2023. Cash, cash equivalents and marketable securities as of June 30, 2024 were $79 million as compared with $108.3 million as of March 31, 2024. We believe our current cash position will be sufficient to fund our anticipated operating expenses and capital expenditure requirements into the third quarter of 2025, bringing us beyond pivotal Phase III data from the SELECT-MD-1 trial and additional data from the randomized portion of the SELECT-AML-1 trial.

我們的研發支出現在主要集中在他米巴羅汀的進展。2024 年第二季的一般管理費用為 550 萬美元，而 2023 年第二季為 720 萬美元。減少的主要原因是員工人數和相關費用、諮詢和設施費用的減少。我們報告 2024 年第二季淨虧損 2,330 萬美元，即每股 0.59 美元，而 2023 年同期淨虧損為 3,630 萬美元，即每股 1.30 美元。截至 2024 年 6 月 30 日，現金、現金等價物及有價證券為 7,900 萬美元，而截至 2024 年 3 月 31 日，現金、現金等價物及有價證券為 1.083 億美元。我們相信，我們目前的現金狀況將足以滿足我們到 2025 年第三季的預期營運費用和資本支出需求，使我們超越 SELECT-MD-1 試驗的關鍵 III 期數據以及來自隨機部分的額外數據。 -AML-1 試驗。

With that, I will turn the call over to the operator for questions.

這樣，我會將電話轉給接線生詢問問題。

(Operator Instructions) Our first question is from Phil Nadeau from Cowen. Please go ahead.

（操作員說明）我們的第一個問題來自 Cowen 的 Phil Nadeau。請繼續。

Thanks for taking our questions. A few from us. First, in AML, when do you think you'd be in position to make a go/no-go decision on advancing tami into a pivotal study in AML? Will the 40 patients we see in September be sufficient? Or would you want to see full data from all 80 patients in the trial?

感謝您回答我們的問題。我們的一些。首先，在 AML 中，您認為什麼時候可以做出是否將 tami 推進 AML 關鍵研究的決定？我們9月看診的40名患者夠用嗎？或者您想查看試驗中所有 80 名患者的完整數據嗎？

Thanks, Phil. David here answering your question. So just to make sure, all who are listening are caught up. We are planning on providing an update on our data from a prespecified analysis of the ongoing SELECT-AML-1 trial that will take place at the upcoming SOHO that's the Society of Hematologic Oncology Annual Meeting in 2024 in September.

謝謝，菲爾。大衛在這裡回答你的問題。所以為了確保所有正在聽的人都能聽懂。我們計劃提供正在進行的 SELECT-AML-1 試驗的預先指定分析的數據更新，該試驗將在即將於 9 月舉行的 SOHO（血液腫瘤學會年會）上進行。

And the analysis is intended to, at this point, include at least 40 patients who were contributing to the prespecified analysis will likely have a slightly larger number of total patients available since the enrollment continued beyond that 40 patient milestone cut point.

此時，分析的目的是包括至少 40 名對預先指定的分析做出貢獻的患者，因為入組繼續超過 40 名患者里程碑截止點，因此可用患者總數可能會稍多一些。

In terms of knowing what the go/no-go and the timing for sharing the plan, I think we really -- we need to see the data. We haven't analyzed the comparative results across the two arms, and it's going to be very important for us to understand what they show for us to better plan, what the next steps are and communicate them out. So it's a bit premature for me to directly answer your question. I hope you appreciate that. And we will as always provide you with updates as soon as we can.

在了解什麼是可行/不可行以及共享計劃的時機方面，我認為我們確實需要查看數據。我們還沒有分析兩個分支的比較結果，了解它們所顯示的內容對於我們更好地規劃、下一步是什麼並將其傳達出來對我們來說非常重要。所以我現在直接回答你的問題還太早。我希望你能欣賞這一點。我們將一如既往地盡快為您提供更新資訊。

And could you give us some sense of what you would want to see to -- decided to move on to a pivotal, what type of delta between the arms or anything else that's important in your decision?

您能否告訴我們您希望看到什麼 - 決定轉向關鍵點，手臂之間的三角洲類型或其他對您的決定很重要的事情？

Well, as you know, we presented data at the end of last year that showed a 100% CR/CRi rate, which included a very high rate of CRs. I think it was 78% of those were CRs and that compared to the control arm of a 70% CR/CRi rate with 30% CR. So obviously, we were very excited about the magnitude of the complete response as well as the complete -- the CR/CRi response.

嗯，如你所知，我們去年年底提供的數據顯示 100% CR/CRi 率，其中包括非常高的 CR 率。我認為其中 78% 是 CR，而對照組的 CR/CRi 率為 70%，CR 率為 30%。顯然，我們對完整反應以及完整的 CR/CRi 反應的強度感到非常興奮。

The difference between those 2 arms is going to be important and also understanding something about the quality of those responses in terms of their duration of the remissions, will all contribute to the way in which we interpret those results. So again, we'll have the data in September. We'll be able to help share what they are and interpret them and provide the context for how we're interpreting them, and you'll better understand what we have at that point in time.

這兩個組別之間的差異非常重要，並且了解這些反應在緩解持續時間方面的質量，都將有助於我們解釋這些結果的方式。同樣，我們將在 9 月獲得數據。我們將能夠幫助分享它們是什麼並解釋它們，並提供我們如何解釋它們的背景，您將更好地理解我們當時所擁有的內容。

Perfect. That's helpful.

完美的。這很有幫助。

And then second. On MDS, you've been very clear on the path to commercialization here in the U.S. Can you remind us about Europe? Is there a path to commercialization in Europe and what would be your plans for marketing the drug overseas?

然後是第二。關於MDS，您對美國這裡的商業化道路非常清楚。在歐洲有商業化的途徑嗎？

Yes. The U.S. market is very focused, and we continue to believe that building an efficient infrastructure will allow us to commercialize in the U.S. In Europe, as you know, it's much more fragmented. And so the idea is to license or find a partner in Europe to execute against that.

是的。美國市場非常集中，我們仍然相信，建立高效的基礎設施將使我們能夠在美國商業化。因此，我們的想法是在歐洲獲得許可或尋找合作夥伴來執行這一目標。

Perfect.

完美的。

Perfect. And then last question for us. Just on the financials. Jason, it looks like the expenses were down this quarter. Was that timing of some expenses.

完美的。然後是我們的最後一個問題。就財務而言。傑森，看來本季的開支有所下降。那是一些費用的時間嗎？

And we should expect expenses in future quarters to be more similar to the past? Or is this the new run rate, have there been some cost-cutting initiatives that -- minor cost-cutting initiatives that have taken expenses down?

我們應該預期未來幾季的支出會與過去更加相似嗎？或者這是新的運行速度，是否有一些成本削減措施——較小的成本削減措施降低了開支？

Yes. I mean at this point, Phil, as I've mentioned before, expenses have been coming down because we did a reprioritization kind of late last year and all of our resources are really focused on getting to the MDS data and the AML data and then starting to prepare for commercial launch once we have data later this year. So I think it's fair to say we're at a new kind of run rate on expenses relative to where we were in years past. We're being pretty judicious on expenses for obvious reasons at this point.

是的。我的意思是，Phil，在這一點上，正如我之前提到的，費用已經下降，因為我們去年年底重新確定了優先級，我們所有的資源都集中在獲取 MDS 數據和 AML 數據上，然後一旦我們在今年稍後取得數據，就開始準備商業發布。因此，我認為可以公平地說，相對於過去幾年，我們的支出運行速度處於一種新的水平。出於顯而易見的原因，我們目前在開支上非常明智。

That's very helpful.

這非常有幫助。

Thanks for taking our questions.

感謝您回答我們的問題。

Our second question will be coming from Ed Tenthoff from Piper Sandler.

我們的第二個問題將來自 Piper Sandler 的 Ed Tenthoff。

My question is just maybe you can give us a reminder on SELECT-MDS. Really enjoyed this -- a couple of weeks out. Remind us what the [power] is for the Phase III trial? And what do you see the delta needed to achieve that.

我的問題是，也許您可以在 SELECT-MDS 上給我們一個提醒。真的很喜歡這個——幾週後。提醒我們三期試驗的[權力]是什麼？您認為實現這一目標所需的三角洲是什麼？

Thanks, Ed.

謝謝，艾德。

Thanks, Ed. This is David, again. If your question, it was a little difficult to hear, but I think you were asking what -- to remind you what the powering was for the Phase III. The primary endpoint is the CR rate and SELECT-MDS-1, and the study is powered to over 90% to show a difference in the CR rates across the 2 arms. We've modeled the powering assumptions based on our 2:1 randomization.

謝謝，艾德。這又是大衛。如果你的問題有點難以聽清，但我認為你在問什麼——提醒你第三階段的動力是什麼。主要終點是 CR 率和 SELECT-MDS-1，研究的有效率超過 90%，以顯示 2 組 CR 率的差異。我們根據 2:1 隨機化對供電假設進行了建模。

And the numbers of patients we need to achieve that power is about approximately 190 patients. We accomplished that enrollment back in the first quarter, and we're anticipating having the pivotal primary readout by the middle of the fourth quarter of this year. So we're really excited about that.

我們需要大約 190 名患者來實現這項能力。我們在第一季就完成了註冊工作，我們預計在今年第四季中期將獲得關鍵的初選結果。所以我們對此感到非常興奮。

The assumptions around how the arms would perform, we've assumed the standard performance for aza for the control arm. And there is significant difference between those was what we took into consideration. We haven't publicly disclosed the numerical assumptions. But keep in mind that there's lots of things that goes into the final readout, which not only includes the CR, but the durability of the response, other secondary endpoints and the overall safety.

關於手臂如何執行的假設，我們假設了控製手臂的 aza 的標準表現。我們考慮到了這些之間存在顯著差異。我們尚未公開揭露數值假設。但請記住，最終讀數涉及許多因素，其中不僅包括 CR，還包括反應的持久性、其他次要終點和整體安全性。

So I think that we'll be able to share as much as we can at the time of our top line, and we anticipate you'll have great context in being able to interpret the trial's ultimate success as we remain hopeful.

因此，我認為我們將能夠在頂線時盡可能多地分享，並且我們預計您將有很好的背景來解釋試驗的最終成功，因為我們仍然充滿希望。

Great. Looking foward to the data in SELECT-MDS in the middle of the fourth quater.

偉大的。期待第四季中段SELECT-MDS的數據。

That's correct.

這是正確的。

Our next question will be coming from Jason Butler from Citizen JPM.

我們的下一個問題將由公民摩根大通 (Citizen JPM) 的傑森巴特勒 (Jason Butler) 提出。

It's Roy on for Jason from Citizen's JMP. Quick one on SELECT-AML-1, the update at SOHO. What duration of follow-up you're going to have for that data?

羅伊 (Roy) 替補來自 Citizen's JMP 的傑森 (Jason)。快速了解 SELECT-AML-1，這是 SOHO 的更新。您將對這些數據進行多長時間的追蹤？

So the study will be reporting on a prespecified analysis. We targeted that prespecified analysis to capture at least 80 -- excuse me, at least 50% of the 80 planned enrolled patients. So we would look forward to having at least 40. There likely will be a slightly larger number than 40 at the time of the report because there was ongoing enrollment subsequent to the date trigger for the prespecified analysis data gathering.

因此，該研究將報告預先指定的分析。我們的目標是進行預先指定的分析，以捕獲計劃納入的 80 名患者中的至少 80 名患者——對不起，至少 50%。所以我們預計至少有 40 個。在報告發佈時，人數可能會比 40 人稍多一些，因為在預定分析資料收集的日期觸發之後，登記仍在繼續。

And in terms of the length of time these patients were on study, these are all parts of the details that will be forthcoming in the September presentation. So obviously, the patients who were part of the study from the initial update that was provided back in -- earlier in the year, will have had a larger opportunity to be followed relative to those who are more recently enrolled but we will be reporting as much as we can at the time.

就這些患者接受研究的時間長度而言，這些都是即將在 9 月的演示中提供的詳細資訊的一部分。很明顯，從今年早些時候提供的初始更新開始，參與研究的患者相對於最近入組的患者將有更大的機會接受隨訪，但我們將報告為盡我們所能。

Okay. Great. And then a couple on SELECT-MDS-1. You have a target forum or a method for presenting the pivotal CR results in 4Q? And can you just give us an enrollment status update for the target patients for survival analysis?

好的。偉大的。然後是 SELECT-MDS-1 上的幾個。您有目標論壇或方法來展示第四季度的關鍵 CR 結果嗎？您能否向我們提供目標患者的最新註冊狀態以進行存活分析？

So we'll be learning about the results from the blinded placebo-controlled randomized trial by the middle of the fourth quarter, and we'll be sharing that as a top line in the ordinary fashion as it would be, obviously, corporate communication of some sort. We haven't specified the nature of any additional presentations or data sharing, but certainly at around that time, we'll provide you with much information as we can.

因此，我們將在第四季度中期之前了解盲法安慰劑對照隨機試驗的結果，並且我們將以普通方式將其作為頂線分享，顯然，這將是企業溝通某種。我們尚未指定任何其他演示或資料共享的性質，但肯定在那時，我們將盡可能為您提供更多資訊。

I will say the study has continued to enroll, and we are seeing, obviously, continued great excitement and interest in the program since we achieved the enrollment target for the primary and endpoint analysis. And we're making good progress is what I'm trying to say toward delivering the total of 550 patients for the survival secondary end point.

我想說的是，這項研究仍在繼續招募，而且自從我們實現了主要和終點分析的招募目標以來，我們顯然看到人們對該計劃的持續極大的興奮和興趣。我想說的是，我們在為 550 名患者提供生存次要終點方面取得了良好進展。

That said, we haven't yet provided more specific information on the timing of the completion of that enrollment or the timing of that analysis. As you know, it's an endpoint-driven analysis. And so it's obviously going to come at a later point in time than the CR analysis, but we haven't been more specific yet.

也就是說，我們尚未提供有關完成註冊時間或分析時間的更多具體資訊。如您所知，這是端點驅動的分析。因此，它顯然會比 CR 分析晚一些，但我們還沒有更具體的資訊。

Okay.

好的。

Thank you.

謝謝。

(Operator Instructions)

（操作員說明）

Our next question will be coming from leisure time from Brookline Capital Markets.

我們的下一個問題將來自布魯克林資本市場的休閒時間。

My question is for David. I'm hoping you can give us some clarity and framework around MDS. So as we think about the high-risk patients versus low-risk patients, can you characterize the difference in how those patients present and what the appropriate endpoints are for studying them and treating them?

我的問題是問大衛的。我希望您能給我們一些有關 MDS 的清晰說明和框架。因此，當我們考慮高風險患者與低風險患者時，您能否描述這些患者表現的差異以及研究和治療他們的適當終點是什麼？

Sure, Leah. Thanks for that question. So the disease you could think of is, is divided into 2 categories of patients, lower risk and higher risk. Really what defines the lower-risk patients is the prognosis. So they have a much longer time horizon until they evolve into a more serious life-threatening disease.

當然，莉亞。謝謝你提出這個問題。因此，您可以想到的疾病分為兩類患者：低風險和高風險。真正定義低風險患者的是預後。因此，它們有更長的時間範圍，直到演變成一種更嚴重的危及生命的疾病。

So the higher risk patients are closer to that point in time. So in general, the risks which are defined by the IPSS-R, the International Prognostic Scoring System that was revised and published by Greenberg and Blood. Details out what those are, and we can certainly get that information to you if you want to look more specifically.

因此，風險較高的患者更接近該時間點。因此，總的來說，IPSS-R（由 Greenberg 和 Blood 修訂和發布的國際預後評分系統）定義的風險。詳細說明這些內容是什麼，如果您想更具體地查看，我們當然可以向您提供這些資訊。

In general, the symptoms of a low-risk patient are related to anemia. And that's the prominent cytopenia that those patients will present with. So they'll often come to the doctor complaining of being weak and fatigued and they have anemia, but their blood looks unusual and they do a marrow and they diagnose dysplasia.

一般來說，低風險患者的症狀與貧血有關。這就是這些患者會出現的明顯的血球減少症。因此，他們經常去看醫生，抱怨身體虛弱、疲勞，並且患有貧血，但他們的血液看起來不正常，他們做了骨髓檢查，診斷出發育不良。

And then the treatments are largely aimed and directed at red blood cell improvement. So some of the endpoints would be associated with hemoglobin concentration increases, just specifically. Later on, when you have high-risk disease, the disease is looking more and more like AML. As you know, those 2 diseases are on a continuum, and they're very similar in that respect. And so there, the problems relate to increased levels of bone marrow blasts and other blood counts that are impacted like the white cells in the platelets.

然後治療主要針對紅血球改善。因此，有些終點可能與血紅素濃度增加有關，只是具體而言。後來，當您患有高風險疾病時，這種疾病看起來越來越像 AML。如您所知，這兩種疾病是一個連續體，在這方面非常相似。因此，問題與骨髓原始細胞水平增加和其他受到影響的血球計數（如血小板中的白血球）有關。

So those patients may have bleeding, infections as well as anemia or they may be having difficulties associated with AML like symptoms. And so the therapies there are largely focused on the endpoints around the complete response rate, which is why we chose that particular endpoint. As you know, the CR is a very important endpoint for MDS drug development because it provides an early read on the efficacy of a drug. It's closely correlated with overall survival.

因此，這些患者可能會出現出血、感染和貧血，或者可能會遇到與 AML 類似症狀相關的困難。因此，那裡的療法主要集中在完全緩解率周圍的終點，這就是我們選擇該特定終點的原因。如您所知，CR 是 MDS 藥物開發的一個非常重要的終點，因為它提供了藥物療效的早期解讀。它與總生存期密切相關。

Hematologic improvement is a very important aspect of the endpoint definition. So when you improve the red count, the white count in platelets, you then can claim you have a CR as long as the blasts have been reduced. So one would also expect an associated, a resolution of a lot of the symptoms that these patients have, which are infections, bleeding and fatigue. And that's why there's short-term benefits to attaining a CR that -- and long-term benefits with survival.

血液學改善是終點定義的一個非常重要的面向。因此，當您改善血小板中的紅色計數和白色計數時，只要原始細胞減少，您就可以聲稱自己已達到 CR。因此，人們也期望這些患者的許多症狀得到解決，包括感染、出血和疲勞。這就是為什麼獲得 CR 會帶來短期好處，而長期生存也會帶來好處。

And that's why the regulators are supportive of its use in making a regulatory decision. So I hope that helps to answer your question. And as you can probably tell, I get very excited when I have a chance to talk about the patients and their disease symptoms and how we can fix them. So we're happy to take more if you have any in the future.

這就是為什麼監管機構支持在監管決策中使用它的原因。所以我希望這有助於回答你的問題。正如您可能知道的那樣，當我有機會談論患者及其疾病症狀以及我們如何解決這些問題時，我感到非常興奮。因此，如果您將來有的話，我們很樂意提供更多。

Most helpful. And what I would infer from that, just to make sure I'm on the right track here is that patients with high-risk disease, you're trying to get their blast count down. So mechanistically, you'd be addressing disease very differently than you would with a low-risk patient, where you're really supporting, primarily the hemoglobin and potentially some other blood lineages, but it would be a very different treatment paradigm for these 2 distinct sets of patients. Am I right?

最有幫助。我從中推斷出，為了確保我走在正確的軌道上，患有高風險疾病的患者，你正在努力減少他們的原始細胞數。因此，從機制上講，您處理疾病的方式與處理低風險患者的方式非常不同，在低風險患者中，您真正支持的主要是血紅蛋白和可能的其他一些血統，但這對於這兩種情況來說將是一種非常不同的治療範例不同的患者群。我說得對嗎？

I think that's a fair way to view it. There's similarities and some of the reasons why a patient with low-risk disease may have a low red blood count. There's a problematic clone of cells that are causing the problems without it leading to anemia. But the therapies that promote increasing the red cell mass are largely the ones that are going to ameliorate the symptoms. They're not always going to be associated with delaying the development of leukemia, but you're treating what you have before you at the time.

我認為這是一種公平的看法。低風險疾病患者的紅血球數量可能較低，這兩者之間存在相似之處和一些原因。有一個有問題的細胞克隆會導致問題，但不會導致貧血。但促進增加紅血球量的療法主要是改善症狀的療法。它們並不總是與延緩白血病的發展有關，但您正在治療當時的情況。

Thank you. Much appreciated.

謝謝。非常感謝。

There are no further questions at this time. I'd now like to turn the call over to Mr. Conley Chee for final closing comments.

目前沒有其他問題。現在我想將電話轉給 Conley Chee 先生以徵求最後的總結意見。

Great. Thanks, operator, and thanks, everyone, for joining us today and for all the great questions. We're looking forward to a very exciting second half of the year. And thank you again for all your continued support. And if you have any questions, please feel free to reach out to us.

偉大的。感謝營運商，感謝大家今天加入我們並提出所有重要問題。我們期待著非常令人興奮的下半年。再次感謝您一直以來的支持。如果您有任何疑問，請隨時與我們聯繫。

Have a great day.

祝你有美好的一天。

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. You all have a good one.

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。你們都有一個很好的。