Crescent Biopharma Inc (CBIO) 2023 Q2 法說會逐字稿

Good morning, and thank you for joining the GlycoMimetics Q2 2023 Earnings Call. At this time all participants are in listen only mode. Following management's remarks, we will hold a question-and-answer session.(Operator Instructions).

早上好，感謝您參加 GlycoMimetics 2023 年第二季度收益電話會議。此時所有參與者都處於只聽模式。管理層發言後，我們將舉行問答環節。（操作員說明）。

I would now like to turn the call over to Christian Dinneen-Long, Company Counsel at GlycoMimetics. Please go ahead.

我現在想將電話轉給 GlycoMimetics 公司法律顧問 Christian Dinneen-Long。請繼續。

Good morning. Today, we will review our business updates and financial results for the quarter ended June 30, 2023. The press release we issued this morning is available on the company's website at glycomimetics.com. This call is being recorded, and a dial-in phone replay will be available for 24 hours after the close of the call. The webcast replay will also be available for 30 days in the Investors section of the company's website. Joining me on the call today from GlycoMimetics are Harout Semerjian, Chief Executive Officer; Brian Hahn, Chief Financial Officer; and Dr. Edwin Rock, Chief Medical Officer.

早上好。今天，我們將回顧截至 2023 年 6 月 30 日的季度的業務更新和財務業績。我們今天上午發布的新聞稿可在公司網站 glumimetics.com 上獲取。此通話正在錄音，通話結束後 24 小時內可進行撥入電話重播。網絡直播重播也將在公司網站的投資者部分提供 30 天的播放。今天與我一起參加 GlycoMimetics 電話會議的是首席執行官 Harout Semerjian；布萊恩·哈恩，首席財務官；和首席醫療官 Edwin Rock 博士。

Today's call will include forward-looking statements based on our current expectations. Forward-looking statements may include, but are not limited to, statements about the company's product candidate uproleselan or other pipeline programs, along with statements about the conduct of and our collaborators' clinical trials, planned potential regulatory agency interactions or submissions, development plans and activities, pre-commercialization preparations, the company's operations, cash position and runway and our expectations regarding data from clinical trials. Such statements represent management's judgment and intention as of today and involve assumptions, risks and uncertainties. GlycoMimetics undertakes no obligation to update or revise any forward-looking statement. For information concerning the risk factors that could affect the company, please refer to our filings with the SEC, which are available from the SEC or through the GlycoMimetics website. I'll now turn the call over to Harout.

今天的電話會議將包括基於我們當前預期的前瞻性陳述。前瞻性陳述可能包括但不限於有關公司產品候選產品 uproleselan 或其他管道計劃的陳述，以及有關我們合作者的臨床試驗的進行、計劃的潛在監管機構互動或提交、開發計劃和活動、商業化前的準備工作、公司的運營、現金狀況和跑道以及我們對臨床試驗數據的期望。此類陳述代表管理層截至目前的判斷和意圖，並涉及假設、風險和不確定性。 GlycoMimetics 不承擔更新或修改任何前瞻性聲明的義務。有關可能影響公司的風險因素的信息，請參閱我們向 SEC 提交的文件，這些文件可從 SEC 或通過 GlycoMimetics 網站獲取。我現在將把電話轉給哈魯特。

Thank you, Christian, and good morning, everyone. This is a transformational time for our company, as we continue to advance our clinical pipeline and to evolve ourselves into a commercial stage organization. Today, we would like to highlight 3 major advancements that position us well for a catalyst-rich upcoming 12 months. First, the FDA cleared a protocol amendment for our Phase III uproleselan study that will enable us to report top line results by the end of Q2 2024. Second, we continue to broaden our clinical development strategy for uproleselan by moving forward with our pediatric development plan and third, we plan to further expand our clinical pipeline and initiate a first-in-human Phase Ia study for GMI-1687 in the third quarter of this year.

謝謝克里斯蒂安，大家早上好。對於我們公司來說，這是一個轉型時期，我們將繼續推進我們的臨床產品線，並將自己發展成為一個商業階段的組織。今天，我們想重點介紹 3 項重大進展，這些進展使我們能夠在充滿催化劑的未來 12 個月中處於有利地位。首先，FDA 批准了我們的III 期uproleselan 研究的方案修正案，這將使我們能夠在2024 年第二季度末報告頂線結果。其次，我們通過推進我們的兒科開發計劃，繼續擴大我們的uproleselan 臨床開發策略第三，我們計劃進一步擴大我們的臨床管線，並於今年第三季度啟動 GMI-1687 的首次人體 Ia 期研究。

These 3 areas of progress, each represent potential long-term value drivers for our company. In June, the FDA cleared the addition of a protocol amendment to our Phase III study of uproleselan for relapsed and refractory acute myeloid leukemia. This amendment adds a time-based analysis option that will enable us to announce top line results by the end of Q2 2024. Final analysis will evaluate effects of uproleselan on relapsed and refractory AML in a clinically mature database with more than 3 years of median follow-up. The analysis will also incorporate at least 2 years of post-transplant data for a large majority of patients remaining on study who received stem cell transplantation. Dr. Ed Rock, our Chief Medical Officer, will provide additional information on the significance of this timing later in this call.

這三個進步領域分別代表了我們公司潛在的長期價值驅動力。 6 月，FDA 批准對我們用於治療復發性和難治性急性髓性白血病的 uproleselan III 期研究添加一項方案修正案。該修正案增加了基於時間的分析選項，使我們能夠在2024 年第二季度末公佈頂線結果。最終分析將在中位隨訪時間超過3 年的臨床成熟數據庫中評估uproleselan 對複發性和難治性AML 的影響-向上。該分析還將納入大多數仍在接受干細胞移植的研究患者的至少 2 年的移植後數據。我們的首席醫療官 Ed Rock 博士將在稍後的電話會議中提供有關這一時機重要性的更多信息。

The option for time-based analysis aligns with regulatory precedent for an approved AML therapy and reflects our commitment to deliver uproleselan to relapse and refractory AML patients in need of new therapy options as soon as possible. With top line results expected by the end of Q2 2024, we continue to pursue precommercialization activities while also advancing additional pipeline programs. We're also proud to expand our uproleselan development strategy by exploring its potential in people with all ages who are living with AML. This past quarter, we achieved 3 key advances in the development of uproleselan for pediatric patients. The FDA agreed to our proposed initial pediatric study plan or IPSP, establishing a regulatory path forward to study uproleselan as a therapeutic option for pediatric AML patients. The NCI notified us that they will initiate a Phase I/II dose escalation study to investigate safety and early activity of uproleselan plus salvage therapy for relapsed and refractory pediatric AML.

基於時間的分析選項符合已批准的 AML 治療的監管先例，並反映了我們致力於盡快為需要新治療方案的複發和難治性 AML 患者提供 uproleselan 的承諾。預計到 2024 年第二季度末將獲得頂線結果，我們將繼續開展預商業化活動，同時推進其他管道項目。我們還很自豪能夠通過探索其在所有年齡段的 AML 患者中的潛力來擴大我們的 uproleselan 發展戰略。上個季度，我們在兒科患者的 uproleselan 開發方面取得了 3 項關鍵進展。 FDA 同意我們提出的初步兒科研究計劃（IPSP），為研究 uproleselan 作為兒科 AML 患者的治療選擇建立了監管路徑。 NCI 通知我們，他們將啟動一項 I/II 期劑量遞增研究，以調查 uproleselan 聯合挽救療法治療復發性和難治性兒童 AML 的安全性和早期活性。

And finally, in June, the first pediatric patient was treated in an investigator-initiated Phase I/II study of uproleselan plus a pre-transplant regimen for AML treatment. This important milestone is the first step in evaluating uproleselan in pediatric patients. The study is being led by Dr. John Horan of the Boston Children's Hospital and Dana Farber Cancer Institute. We're grateful that the NCI and Boston Children's Hospital teams are assessing uproleselan for treatment of pediatric AML patients. And we look forward to learning more about its potential impact in this vulnerable patient population.

最後，在 6 月，第一例兒科患者在一項由研究者發起的 I/II 期研究中接受了治療，該研究採用 uproleselan 加上移植前治療方案來治療 AML。這一重要的里程碑是評估兒科患者烏普羅塞蘭的第一步。該研究由波士頓兒童醫院和達納法伯癌症研究所的約翰霍蘭博士領導。我們很高興 NCI 和波士頓兒童醫院團隊正在評估 uproleselan 對兒科 AML 患者的治療效果。我們期待更多地了解其對這一弱勢患者群體的潛在影響。

In the third quarter, we plan to initiate a Phase Ia study of GMI-1687 in healthy volunteers to evaluate the drug safety, tolerability and pharmacokinetics. GMI-1687 is a second-generation E-selectin antagonist with potential users in diverse inflammatory diseases. Our initial focus will be on sickle cell disease. GMI-1687 has been shown in preclinical models to be highly subcutaneously bioavailable. And this Phase Ia study is a vital first step in its clinical development.

第三季度，我們計劃在健康志願者中啟動GMI-1687的Ia期研究，以評估藥物的安全性、耐受性和藥代動力學。 GMI-1687 是第二代 E-選擇素拮抗劑，具有治療多種炎症性疾病的潛在用途。我們最初的重點是鐮狀細胞病。 GMI-1687 已在臨床前模型中顯示出具有高度皮下生物利用度。這項 Ia 期研究是其臨床開發至關重要的第一步。

Turning to our finances, we have a cash runway to fund operations late into the fourth quarter of 2024. So we're well positioned to continue executing our clinical development plan. Our pivotal Phase III trial in relapsed and refractory AML remains on track for a top line readout at the end of Q2 2024. And we will begin a Phase Ia study of GMI-1687 in the coming weeks. On today's call, I'm happy to be joined by our CFO, Brian Hahn; and CMO, Dr. Ed Rock. Ed, I'll now pass it on to you to share more details on our ongoing trials.

談到我們的財務狀況，我們有現金跑道為 2024 年第四季度末的運營提供資金。因此，我們有能力繼續執行我們的臨床開發計劃。我們針對複發性和難治性 AML 的關鍵 III 期試驗仍有望在 2024 年第二季度末公佈頂線結果。我們將在未來幾週內開始 GMI-1687 的 Ia 期研究。我很高興邀請我們的首席財務官 Brian Hahn 參加今天的電話會議。首席營銷官 Ed Rock 博士。艾德，我現在將其傳遞給您，以分享有關我們正在進行的試驗的更多細節。

Thanks, Harout, and thanks to all of you on the line for joining our call today. Our recent protocol amendment to the uproleselan Phase III trial in relapsed and refractory AML will allow a time-based primary analysis of overall survival. Time-based analysis will occur after a defined cutoff date if the 295 survival events originally planned for event-driven analysis are not observed by that date. As Harout mentioned, top line results are expected by the end of Q2 2024. Median follow-up for this trial will be over 3 years at the time of top line analysis in Q2 2024. That's unprecedented for a therapeutic trial in relapsed and refractory AML.

謝謝哈魯特，也感謝所有在線的人今天加入我們的電話會議。我們最近對複發性難治性 AML 的 uproleselan III 期試驗進行了方案修訂，將允許對總生存期進行基於時間的初步分析。如果最初計劃用於事件驅動分析的 295 個生存事件在該日期之前未觀察到，則將在定義的截止日期後進行基於時間的分析。正如Harout 提到的，預計將在2024 年第二季度末獲得頂線結果。截至2024 年第二季度頂線分析時，該試驗的中位隨訪時間將超過3 年。這對於復發和難治性AML 的治療試驗來說是前所未有的。

We completed enrollment of the study in 388 patients in November 2021. Correspondingly, primary survival analysis of uproleselan benefit in relapsed and refractory AML will be based on a clinically mature data set. That's because a substantial majority of surviving patients on study received stem cell transplantation and almost all of these transplant recipients will have a minimum 2 years of post-transplant follow-up at the time of analysis. As you know, allogeneic stem cell transplantation is the only known curative therapy for acute myeloid leukemia. 2 years post-transplant is an important milestone in that after 2 years, the graft versus leukemia effect of stem cell transplantation has had time to develop fully. As a result, incidence of AML relapse after 2 years post-transplant is low, and these patients may be considered cured of their AML. Risk persists in this population, primarily for non-AML mortality, including from infections and graft versus host disease. Still, after 2 years post-transplant, disease relapse becomes infrequent, and disease relapse is, of course, what uproleselan is intended to prevent.

我們於 2021 年 11 月完成了 388 名患者的研究入組。相應地，uproleselan 對複發和難治性 AML 益處的主要生存分析將基於臨床成熟的數據集。這是因為參與研究的絕大多數存活患者都接受了乾細胞移植，並且在分析時幾乎所有這些移植接受者都將接受至少 2 年的移植後隨訪。如您所知，同種異體幹細胞移植是治療急性髓系白血病的唯一已知療法。移植後2年是一個重要的里程碑，因為2年後，幹細胞移植的移植物抗白血病作用已經有時間充分發揮。因此，移植後 2 年後 AML 復發的發生率較低，這些患者的 AML 可能被認為已治愈。該人群仍然存在風險，主要是非 AML 死亡率，包括感染和移植物抗宿主病。儘管如此，移植後 2 年後，疾病復發變得很少見，而疾病復發當然正是 uproleselan 的目的。

Accordingly, the company believes capture of survival events after Q2 2024 would provide only limited additional value for primary analysis. As a result, GlycoMimetics believes that Q2 2024 provides a clinically optimal time to confirm uproleselan benefit in relapsed and refractory AML. The RATIFY trial of midostaurin in newly diagnosed FLT3 mutant AML patients less than 60 years of age provides a regulatory precedent for our path forward. In RATIFY, as in our trial, interim analysis led to a data monitoring committee recommendation to continue the study. In both trials, death events slowed appreciably after interim analysis. Once it became evident in RATIFY that the planned primary endpoint events trigger might not be reached, the sponsor added a time-based final analysis.

因此，該公司認為，捕獲 2024 年第二季度之後的生存事件只能為初步分析提供有限的附加價值。因此，GlycoMimetics 認為 2024 年第二季度提供了一個臨床最佳時間來確認 uproleselan 對複發和難治性 AML 的益處。在新診斷的 60 歲以下 FLT3 突變 AML 患者中進行的米斯託林 RATIFY 試驗為我們的前進道路提供了監管先例。在 RATIFY 中，正如我們的試驗一樣，中期分析導致數據監測委員會建議繼續研究。在這兩項試驗中，中期分析後死亡事件明顯放緩。一旦在 RATIFY 中發現可能無法達到計劃的主要終點事件觸發點，申辦者就添加了基於時間的最終分析。

In our protocol amendment, FDA also cleared addition of Landmark event-free and overall survival analysis as secondary end points. These unpowered metrics will provide patients and health care providers with clear, clinically important comparisons of uproleselan versus placebo. FDA in Q2 also agreed to our initial pediatric study plan or IPSP for uproleselan. As part of this IPSP, the National Cancer Institute will conduct a Phase I/II trial of uproleselan plus chemotherapy for pediatric patients with relapsed and refractory AML. This study is nearly open for enrollment of up to an expected 18 patients and each patient will receive 15 doses of uproleselan over 8 days plus fludarabine and cytarabine.

在我們的方案修訂中，FDA 還批准添加 Landmark 無事件分析和總體生存分析作為次要終點。這些無動力指標將為患者和醫療保健提供者提供烏普羅塞蘭與安慰劑之間清晰的、具有臨床意義的比較。 FDA 在第二季度還同意了我們針對 uproleselan 的初步兒科研究計劃或 IPSP。作為該 IPSP 的一部分，美國國家癌症研究所將為患有復發性和難治性 AML 的兒科患者進行 uproleselan 聯合化療的 I/II 期試驗。這項研究即將開放，預計招募最多 18 名患者，每位患者將在 8 天內接受 15 劑烏普羅塞蘭加氟達拉濱和阿糖胞苷。

This trial will assess uproleselan safety, pharmacokinetics and preliminary efficacy in this population. Adult and pediatric AML are expected to have similar E-selectin biology with chemo resistance driven by AML blast binding to bone marrow endothelial cells. So we're excited to evaluate uproleselan with the National Cancer Institute in this study. Finally, Dr. John Horan of Boston Children's Hospital, is leading a new single-arm multicenter Phase I/II trial of uproleselan combined with pre-stem cell transplant conditioning for patients with chemotherapy resistant AML. This investigator-sponsored trial will describe safety, tolerability and recommended Phase II dose of uproleselan plus busulfan, clofarabine and fludarabine chemotherapy.

該試驗將評估 uproleselan 在該人群中的安全性、藥代動力學和初步療效。成人和兒童 AML 預計具有相似的 E-選擇素生物學特性，並具有由 AML 母細胞與骨髓內皮細胞結合驅動的化療耐藥性。因此，我們很高興在這項研究中與國家癌症研究所一起評估 uproleselan。最後，波士頓兒童醫院的 John Horan 博士正在領導一項新的單臂多中心 I/II 期試驗，將 uproleselan 與乾細胞移植前調理相結合，治療化療耐藥的 AML 患者。這項由研究者資助的試驗將描述烏普羅塞蘭聯合白消安、氯法拉濱和氟達拉濱化療的安全性、耐受性和推薦的 II 期劑量。

The first patient treated in this study recently received uproleselan and is our first ever pediatric patient treated. Recent progress in pediatric development underscores our commitment to explore uproleselan's potential to help AML patients of all ages. We're excited to expand uproleselan's potential utility to pediatric patients and look forward to sharing more information with you as these studies advance.

本研究中治療的第一位患者最近接受了烏普羅塞蘭治療，也是我們治療的第一位兒科患者。兒科開發的最新進展強調了我們致力於探索 uproleselan 幫助所有年齡段 AML 患者的潛力。我們很高興能夠擴大 uproleselan 對兒科患者的潛在效用，並期待隨著這些研究的進展與您分享更多信息。

Now regarding our GlycoMimetics study drug platform, we are proud to share that we will initiate a Phase Ia single ascending dose trial of GMI-1687 later this quarter. GMI-1687 is a potent subcutaneously bioavailable E-selectin antagonist. This second-generation glycomimetic compound has potential applications in multiple inflammatory diseases. Our initial development focus will be on interruption of sickle cell disease vaso-occlusive crises since E-selectin appears to play a major role in pathology of these acute painful episodes. Proof of mechanism preclinical studies show attenuation of VOCs by GMI-1687 in 2 separate mouse models of sickle cell disease.

現在，關於我們的 GlycoMimetics 研究藥物平台，我們很自豪地宣布，我們將於本季度晚些時候啟動 GMI-1687 的 Ia 期單劑量遞增試驗。 GMI-1687 是一種有效的皮下生物可利用的 E-選擇素拮抗劑。這種第二代糖模擬化合物在多種炎症性疾病中具有潛在的應用。我們最初的開發重點將是中斷鐮狀細胞病血管閉塞危機，因為 E-選擇素似乎在這些急性疼痛發作的病理學中發揮著重要作用。臨床前研究的機制證明表明，GMI-1687 在 2 個不同的鐮狀細胞病小鼠模型中可減弱 VOC。

Studies in nonhuman primates confirm its high subcutaneous bioavailability. Our first in human single-dose trial will assess GMI-1687 safety, tolerability and pharmacokinetics and pharmacodynamics in healthy volunteers. PK and PD data from this Phase Ia trial will support design of treatment regimens for multiple inflammatory disease indications. Subcutaneous GMI-1687 may enable patient self-administration at home. If successful, that would reduce need for intravenous therapy in sickle cell vaso-occlusive crises and provide a patient-controlled point-of-care treatment option available at pain crisis onset. Thus, GMI may uniquely offer a differentiated approach with potential to interrupt vaso-occlusive crisis events at time of onset. Now I'll turn it over to Brian for a review of financial results.

對非人類靈長類動物的研究證實了其高皮下生物利用度。我們的首次人體單劑量試驗將評估 GMI-1687 在健康志願者中的安全性、耐受性以及藥代動力學和藥效學。該 Ia 期試驗的 PK 和 PD 數據將支持多種炎症性疾病適應症的治療方案設計。皮下注射 GMI-1687 可以讓患者在家中自行給藥。如果成功，這將減少鐮狀細胞血管閉塞危機中對靜脈注射治療的需求，並在疼痛危機發作時提供患者控制的護理點治療選擇。因此，GMI 可能獨特地提供一種差異化方法，有可能在血管閉塞危機事件發生時中斷該事件。現在我將把它交給布萊恩來審查財務結果。

Thank you, Ed. As of June 30, 2023, GlycoMimetics had cash and cash equivalents of $58 million as compared to $47.9 million as of December 31, 2022. The company's research and development expenses were $4.1 million for the quarter ended June 30, 2023, as compared to $8 million for the same period in 2022. The decreased expenses were primarily due to lower clinical trial and development costs related to our global Phase III clinical trial of uproleselan in individuals of relapsed/refractory AML, which completed enrollment in November 2021. The company's general and administrative expenses decreased to $4.9 million for the quarter ended June 30, 2023, as compared to $5.5 million for the same period in 2022. The reduction was primarily due to lower outside consulting and professional expenses, partially offset by commercial readiness planning expenses for uproleselan.

謝謝你，艾德。截至2023年6月30日，GlycoMimetics擁有現金和現金等價物為5800萬美元，而截至2022年12月31日為4790萬美元。截至2023年6月30日的季度，該公司的研發費用為410萬美元，而截至2022年12月31日，該公司的研發費用為8美元2022 年同期為100 萬美元。費用減少主要是由於與我們針對複發/難治性AML 個體的uproleselan 全球III 期臨床試驗相關的臨床試驗和開發成本較低，該試驗於2021 年11 月完成入組。截至2023 年6 月30 日的季度，管理費用減少至490 萬美元，而2022 年同期為550 萬美元。減少的主要原因是外部諮詢和專業費用減少，但被uproleselan 的商業準備規劃費用部分抵消。

Given that we now have definitive timing for our data readout by the end of second quarter 2024, we will be able to utilize budget contingencies to advance the first-in-human study of GMI-1687 while maintaining our anticipated cash burn of roughly $10 million per quarter with cash runway into late fourth quarter 2024. I'd now like to turn the call back to Harout.

鑑於我們現在已經確定了在 2024 年第二季度末之前讀出數據的確切時間，我們將能夠利用預算意外事件來推進 GMI-1687 的首次人體研究，同時保持我們預計的約 1000 萬美元的現金消耗每季度現金跑道持續到2024 年第四季度末。我現在想把電話轉回哈魯特。

Thank you, Brian. So in summary, the GlycoMimetics team continues to execute on our plan. Together, we achieved multiple milestones in the last quarter that can drive long-term value for our organization, including reaching an agreement with FDA to add the option of a time-based analysis to our Phase III study of uproleselan, which will enable us to announce top line results by the end of Q2 2024. Initiating research of uproleselan in pediatric patients with the announcement of the trials led by the NCI and Dana Farber Cancer Institute; and last, broadening our pipeline to advance GMI-1687 to a first-in-human study. With a cash runway to fund operations late into fourth quarter of 2024, GlycoMimetics is well positioned for a catalyst-rich next 12 months. I look forward to sharing more updates on future calls. I'd now like to open the lines to Q&A.

謝謝你，布萊恩。總而言之，GlycoMimetics 團隊將繼續執行我們的計劃。我們在上個季度共同實現了多個里程碑，這些里程碑可以為我們的組織帶來長期價值，包括與 FDA 達成協議，在我們的 uproleselan III 期研究中添加基於時間的分析選項，這將使我們能夠於2024 年第二季度末公佈主要結果。宣布由NCI 和Dana Farber 癌症研究所領導的試驗啟動了uproleselan 在兒科患者中的研究；最後，拓寬我們的研發管線，將 GMI-1687 推進至首次人體研究。 GlycoMimetics 擁有為 2024 年第四季度末的運營提供資金的現金跑道，因此在未來 12 個月的催化劑豐富的情況下處於有利地位。我期待在未來的通話中分享更多更新。我現在想打開問答線路。

(Operator Instructions) Our first question comes from the line of Boris Peaker of TD Cowen. Boris, your line is now open.

（操作員說明）我們的第一個問題來自 TD Cowen 的 Boris Peaker。鮑里斯，您的線路現已開通。

This is Nick, on for Boris. Just a queue for me. For the Phase II/III NGI trial for upro will they also be running a time-based analysis similar to what you guys are running for your Phase III trial? Or are they still keeping with their original plan for their analysis and then also, just like a separate question, but for the pediatric patients for upro, what's the plan following the Phase I/II trial? Will the NCI continue to run trials? Or will you guys then take it after the Phase I/II?

我是尼克，替鮑里斯發言。對我來說只是一個隊列。對於 upro 的 II/III 期 NGI 試驗，他們是否也會運行基於時間的分析，類似於你們為 III 期試驗運行的分析？或者他們仍然堅持原來的分析計劃，然後，就像一個單獨的問題一樣，但是對於 UPRO 的兒科患者，I/II 期試驗之後的計劃是什麼？ NCI 會繼續進行試驗嗎？或者你們會在第一階段/第二階段之後服用它嗎？

Thank you, Nick. Thanks for the question. Maybe I'll start off and then move it over to Ed. Regarding the NCI trial in the Phase II/III, what we know is they're still consistent with what we have communicated last quarter, is that they have not reached their events. So I think we're going to have to wait for that and see where they go next. They haven't -- we're not aware of anything beyond that. So what we know is that a predetermined number of events EFS has not been reached. So that's been also communicated to us recently. Maybe, Ed, do you want to add more color on that one and then on the pediatric plan.

謝謝你，尼克。謝謝你的提問。也許我會先開始，然後將其移交給埃德。關於第二/第三階段的 NCI 試驗，我們知道他們仍然與我們上季度傳達的內容一致，他們還沒有達到他們的活動。所以我認為我們將不得不等待，看看他們下一步會去哪裡。他們沒有——我們不知道除此之外的任何事情。所以我們知道 EFS 事件的預定數量尚未達到。最近也向我們傳達了這一點。艾德，也許你想在那個計劃和兒科計劃上添加更多色彩。

Sure. Importantly, that trial's Phase II analysis, which is pending will be based on event-free survival rather than overall survival, both of the randomized trials, completed enrollment in late 2021, so both have been -- have taken a good long time to mature over 18 months. We don't anticipate that the NCI will change their analytic plan to change from an event based EFS analysis to a time-based EFS analysis. And then for the second question about NCI's plans beyond the pediatric Phase I/II, those have not yet been decided definitively, and we'll disclose that information when it's available.

當然。重要的是，該試驗的 II 期分析（正在等待）將基於無事件生存期而不是總生存期，這兩項隨機試驗均於 2021 年底完成入組，因此兩項試驗都需要很長時間才能成熟超過18個月。我們預計 NCI 不會改變其分析計劃，從基於事件的 EFS 分析更改為基於時間的 EFS 分析。關於第二個問題，關於 NCI 在兒科 I/II 期之外的計劃，這些計劃尚未最終決定，我們將在有信息時披露該信息。

(Operator Instructions) Our next question comes from the line of Roger Song of Jefferies.

（操作員說明）我們的下一個問題來自 Jefferies 的 Roger Song。

Great. A couple from us. The first one is regarding the uproleselan, R/R AML pivotal study, had the team taken other look at the data, and how did that tracking your modeling? I understand now it's time based, but have you ever additional kind of data lock. I think on the call, you mentioned most of the survivor they are post-transplant. So any additional color you can provide to us?

偉大的。我們的一對。第一個是關於 uproleselan、R/R AML 關鍵研究，團隊是否對數據進行了其他研究，以及如何跟踪您的建模？我知道現在它是基於時間的，但是您是否有其他類型的數據鎖。我想您在電話中提到了大多數移植後的倖存者。那麼您可以向我們提供任何其他顏色嗎？

Yes. Thank you, Roger. Yes. I mean, the trial continues, patients continue to live longer in this trial. So obviously, as you know, we are blinded -- we do take a look at the pooled blinded data, and we're excited that we have now this option of the time-based analysis should the 295 events not be reached by next year, we believe we're going to have a mature database given the 3 years median follow-up, given the 2 years plus of post-transplant follow-up as well for the vast majority of patients that we're going to have a mature database. So things continue to be on track. Patients continue to live longer. Obviously, we don't know who's on what arm but we're very encouraged by this update and the fact that now we have the option of the time-based analysis on top gives us certainty, clarity and of course, on a database that is going to be mature.

是的。謝謝你，羅傑。是的。我的意思是，試驗仍在繼續，患者在試驗中繼續活得更長。很明顯，如您所知，我們是盲目的 - 我們確實查看了匯總的盲數據，我們很高興我們現在有了基於時間的分析選項，如果明年還沒有達到 295 個事件的話，我們相信，考慮到中位隨訪3 年，考慮到移植後隨訪2 年以上，我們將擁有一個成熟的數據庫，對於絕大多數患者，我們將擁有一個成熟的數據庫。數據庫。所以事情繼續步入正軌。患者的壽命繼續延長。顯然，我們不知道誰在哪個手臂上，但我們對這次更新感到非常鼓舞，事實上，現在我們可以選擇基於時間的分析，這給了我們確定性、清晰度，當然，在數據庫上即將成熟。

Excellent. And regarding the 1687, so what do you expect to see the healthy volunteer data? And how would that support the next step and do you have any timing and maybe the strategic plan in terms of you will take this on your own or you will seek in partner to move forward.

出色的。那麼對於1687，您期望看到的健康志願者數據是什麼？這將如何支持下一步，你是否有任何時間安排，也許你的戰略計劃將由你自己承擔，或者你將尋求合作夥伴來前進。

Yes. Excellent question, Roger. I mean, as you know, 1687 for folks on the phone, it's clear this other asset that we have cleared IND back in June of last year. And given where the markets were, the financial constraints we had, we really had to double down on our Phase III. We're very excited now to be able to be in a situation where we are able to start the Phase Ia of 1687, a compound we believe in. We have deep expertise, as you know, in this area in sickle cell and bringing that expertise on our second generation E-selectin antagonist that is potent and subcutaneously bioavailable. So the first step of that, Roger, as you know, is that single ascending dose, as Ed mentioned.

是的。很好的問題，羅傑。我的意思是，如您所知，對於打電話的人來說，1687，很明顯我們早在去年 6 月就已經批准了 IND 的另一項資產。考慮到市場所在、我們面臨的財務限制，我們確實必須在第三階段加倍努力。我們現在非常高興能夠啟動 1687 的 Ia 期研究，這是我們所相信的化合物。如您所知，我們在鐮狀細胞這一領域擁有深厚的專業知識，並將其我們的第二代E-選擇素拮抗劑的專業知識，該拮抗劑有效且具有皮下生物利用度。所以，羅傑，正如你所知，第一步是單次遞增劑量，正如埃德提到的那樣。

And really, it's a healthy volunteer study. So I don't want to read more into it than what it is. It's really to give us the PK/PD safety signals, which are really needed on the first step. And quite honestly, regardless of what indications we go that single ascending dose trial in the Phase Ia is very consistent and same. So we're going to be doing this. Typically, these volunteer trials they don't take that much time, but it's usually in the months. So sometime, I would say, next year, we should have that information. It's just too early to tell now. Let's get started. As we're announcing today, we are planning to start. We haven't started yet. So let's get started, and we'll keep the market updated about it. But I'm very excited about the ability to start 1687 and put yet another GlycoMimetics product in a first-in-human study in the marketplace.

事實上，這是一項健康的志願者研究。所以我不想對其進行更多的解讀。它實際上是為我們提供第一步真正需要的 PK/PD 安全信號。老實說，無論我們有什麼跡象，Ia 期的單次劑量遞增試驗都是非常一致和相同的。所以我們將這樣做。通常，這些志願者試驗不會花費太多時間，但通常需要幾個月的時間。所以我想說，明年的某個時候，我們應該會得到這些信息。現在說還為時過早。讓我們開始吧。正如我們今天宣布的，我們計劃開始。我們還沒有開始。那麼讓我們開始吧，我們將及時向市場通報最新情況。但我對能夠啟動 1687 並將另一款 GlycoMimetics 產品投入市場上的首次人體研究感到非常興奮。

Got it. Maybe just after the single ascending dose, so what will be the next step and strategic plan in terms of your own versus partner with follow-up on that.

知道了。也許就在單次遞增劑量之後，那麼就您自己與合作夥伴而言，下一步和戰略計劃是什麼以及後續行動。

Yes. I mean it's too early to say, Roger. I mean, regardless if we're going to be doing it ourselves or we're going to be partnering, we need this data anyway. And the fact that we're able to fund it, we're able to move this forward, it's a great, great step. As we've said multiple times, we're always open to partnership conversations, but we don't really have to in a way, the partner has to bring beyond just, the cash has to bring in that expertise, dedication to sickle cell.

是的。我的意思是現在說還為時過早，羅傑。我的意思是，無論我們是自己做還是合作，我們都需要這些數據。事實上，我們能夠為其提供資金，我們能夠推動這一進程，這是非常非常偉大的一步。正如我們多次說過的，我們始終對合作夥伴對話持開放態度，但我們實際上不必以某種方式這樣做，合作夥伴必須帶來的不僅僅是現金，還必須帶來專業知識，對鐮狀細胞病的奉獻。

This is an area where we've seen prophylactic measures, let's say, have humbling uptakes over the last few years. And on the other side of the spectrum, gene therapies, which are very exciting, I wonder how many patients would actually benefit from that. So we do believe that the vast majority of this patient population, unfortunately, will continue to have vaso-occlusive crisis and providing an option that is on demand at the start of that vaso-occlusive crisis is going to be a tremendous help for this patient population. So while we hope that there is multiple different approaches, we do believe that this approach will have a market for it. But of course, before getting ahead of ourselves, first, let's start the single-ascending dose trials. Let's get that going. Let's continue the conversations as well with people who are very motivated in doing trials in sickle cell disease and that medical community is very active. That patient community is very active. So we look forward to partnering with them and potentially other institutions if that works for us and for them. But meanwhile, we have gotten the ball going.

可以說，在過去幾年中，我們在這個領域看到了預防措施取得了令人矚目的進展。另一方面，基因療法非常令人興奮，我想知道有多少患者實際上會從中受益。因此，我們確實相信，不幸的是，絕大多數患者將繼續患有血管閉塞危機，並且在血管閉塞危機開始時提供按需選擇將為該患者提供巨大幫助人口。因此，雖然我們希望有多種不同的方法，但我們確實相信這種方法會有市場。當然，在超前之前，首先讓我們開始單次劑量遞增試驗。讓我們開始吧。讓我們繼續與那些非常積極地進行鐮狀細胞病試驗並且醫學界非常活躍的人們進行對話。該患者社區非常活躍。因此，如果這對我們和他們都有效，我們期待與他們以及其他潛在的機構合作。但與此同時，我們已經開始行動了。

Thank you all. I apologize. There is slight disconnection. I believe it is time to wrap up. So now we can turn it back over to Harout. We are done with questions for now. Harout, it is on for you.

謝謝你們。我道歉。有輕微斷線現象。我相信是時候結束了。所以現在我們可以把它轉回哈魯特。我們現在已經完成了問題。哈魯特，它適合你。

Thank you very much, and thank you to everyone for joining our call today. We look forward to keeping you updated on GlycoMimetics and seeing some of you at the H.C. Wainwright Healthcare Conference in September.

非常感謝，也感謝大家今天加入我們的電話會議。我們期待為您提供有關 GlycoMimetics 的最新信息，並期待在 H.C.九月溫賴特醫療保健會議。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝您參加今天的會議。這確實結束了該程序。您現在可以斷開連接。