Crescent Biopharma Inc (CBIO) 2023 Q4 法說會逐字稿

Good morning, and thank you for joining the GlycoMimetics Q4 and full year 2023 earnings call. (Operator Instructions) I would now like to turn the call over to Christian Dinneen Long company counsel at GlycoMimetics. Please go ahead.

早安，感謝您參加 GlycoMimetics 第四季和 2023 年全年財報電話會議。（操作員說明）我現在想將電話轉給 GlycoMimetics 的 Christian Dinneen Long 公司法律顧問。請繼續。

Good morning. Today we will review our business updates and financial results for the quarter and year ended December 31, 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. On the call today from GlycoMimetics are Harout Semerijian, Chief Executive Officer, Brian Hahn, Chief Financial Officer, Edwin Rock, Chief Medical Officer, and Bruce Johnson, Chief Commercial Officer.

早安.今天，我們將回顧截至 2023 年 12 月 31 日的季度和年度的業務更新和財務表現。我們今天早上發布的新聞稿可在該公司網站 glumimetics.com 上取得。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。網路直播重播也將在公司網站的投資者部分提供 30 天的播放。今天參加 GlycoMimetics 電話會議的有執行長 Harout Semerijian、財務長 Brian Hahn、首席醫療官 Edwin Rock 和首席商務官 Bruce Johnson。

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 candidates used for Uproleselan and GMI-1687, the progress and timing of clinical trials being conducted by us or our collaborators, including our expectations regarding data readout from those trials.

今天的電話會議將包括基於我們目前預期的前瞻性陳述。前瞻性聲明可能包括但不限於有關公司用於 Uproleselan 和 GMI-1687 的候選產品的聲明、我們或我們的合作者正在進行的臨床試驗的進展和時間安排，包括我們對這些試驗數據讀出的期望。

Central potential regulatory agency interactions are submissions, development plans and activities, prelaunch preparations and the company's cash position and runway. 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 statements. 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.

潛在的監管機構互動的核心是提交材料、開發計劃和活動、啟動前的準備工作以及公司的現金狀況和跑道。此類陳述代表管理階層截至目前的判斷和意圖，並涉及假設、風險和不確定性。Glycomitics 不承擔更新或修改任何前瞻性陳述的義務。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 或透過 GlycoMimetics 網站取得。

I'll now turn the call over to Harout.

我現在將把電話轉給哈魯特。

Thank you, Christian, and good morning, everyone. In 2023, we made great strides on the path towards becoming a commercial company building on the advances we made in 2023. I believe 2024 will be a transformational year for our GlycoMimetics. In the second quarter of this year, we expect to report top line results from our Phase 3 trial of our lead drug candidate, Uproleselan.

謝謝克里斯蒂安，大家早安。2023 年，我們在 2023 年取得的進步的基礎上，在成為商業公司的道路上取得了長足的進步。我相信 2024 年對我們的 GlycoMimetics 來說將是轉型的一年。今年第二季度，我們預計將報告我們的主要候選藥物 Uproleselan 的 3 期試驗的主要結果。

This is a significant milestone that can fundamentally impact our company's trajectory while potentially helping patients affected with relapsed and refractory acute myeloid leukemia to live longer.

這是一個重要的里程碑，可以從根本上影響我們公司的發展軌跡，同時有可能幫助患有復發性和難治性急性髓性白血病的患者延長壽命。

I want to thank the entire GlycoMimetics team, our shareholders, collaborators, investigators, trial sites and patients for their trust commitment and resilience during this multiyear Phase 3 trial, which has now reached clinical maturity. Thanks to everyone's combined efforts, we are now very close to unblinding this pivotal trial and should the data supported, we are ready to execute next steps rapidly.

我要感謝整個 GlycoMimetics 團隊、我們的股東、合作者、研究人員、試驗中心和患者在這項多年期 3 期試驗中的信任承諾和韌性，該試驗現已達到臨床成熟。感謝大家的共同努力，我們現在已經非常接近揭開這項關鍵試驗的空白，如果數據得到支持，我們準備好快速執行下一步。

Today, I would like to highlight three key strategic areas driving the transformation of GlycoMimetics. First, based on our prior alignment with the FDA, we are triggering the time-based analysis for our pivotal Phase 3 trial of e uproleselan in relapsed and refractory AML and expect top line results in Q2 2024. We remain encouraged by the median follow-up time, which is now well over three years, remarkably long for the relapsed and refractory population. Pending positive results we expect to submit a new drug application in the US by the end of this year.

今天，我想強調推動 GlycoMimetics 轉型的三個關鍵策略領域。首先，根據我們先前與 FDA 的合作，我們正在啟動 e uproleselan 治療復發性和難治性 AML 關鍵 3 期試驗的基於時間的分析，並預計在 2024 年第二季度獲得頂線結果。我們仍然對中位追蹤時間感到鼓舞，目前中位追蹤時間已超過三年，對於復發和難治性人群來說非常長。在等待積極結果之前，我們預計將於今年年底在美國提交新藥申請。

Second, we are further advanced. We have further advanced our commercial readiness and continue to execute critical prelaunch activities, including the expansion of our commercial and medical affairs capabilities and educational disease awareness activities. And third, we completed the Phase 1a first-in-human trial for GMI-1687, a second-generation E-selectin antagonist being evaluated as an outpatient self-administered subcutaneous therapy to potentially alleviate sickle cell vaso-occlusive events. I'm excited to share that our Phase1a has met its primary and secondary endpoints with no dose-limiting toxicities or other safety signals.

二是我們進一步先進。我們進一步推進了商業準備工作，並繼續執行重要的啟動前活動，包括擴大我們的商業和醫療事務能力以及教育疾病意識活動。第三，我們完成了GMI-1687 的1a 期首次人體試驗，GMI-1687 是一種第二代E-選擇素拮抗劑，正在評估作為一種門診自我皮下療法，有可能緩解鐮狀細胞血管閉塞事件。我很高興地告訴大家，我們的 Phase1a 已經達到了主要和次要終點，沒有劑量限制性毒性或其他安全訊號。

As we look ahead to 2024 and beyond, we believe GlycoMimetics is well positioned to deliver innovative glyco biology based medicines to patients in need of new treatment options, beginning with Uproleselan.

展望 2024 年及以後，我們相信 GlycoMimetics 處於有利地位，可以從 Uproleselan 開始，為需要新治療選擇的患者提供基於糖生物學的創新藥物。

Despite recent advancements in AML therapies, there remains a significant unmet patient need, especially in terms of bending the survival curve upwards for relapsed and refractory patients. With pulp with positive pivotal data, your cholesterol has the potential to prolong survival for patients with relapse and refractory AML. This initial setting has a $650 million to $850 million near term potential market opportunity in the US alone, which could more than double when considering the frontline AML market.

儘管最近在 AML 治療方面取得了進展，但患者的需求仍然有很大的未滿足，特別是在使復發和難治性患者的生存曲線向上彎曲方面。憑藉具有積極關鍵數據的紙漿，您的膽固醇有可能延長復發性和難治性 AML 患者的生存期。這個初始設定僅在美國就有 6.5 億至 8.5 億美元的近期潛在市場機會，考慮到一線 AML 市場，這一數字可能會增加一倍以上。

Our important partnerships with MD Anderson, the National Cancer Institute and the Dana-Farber Cancer Institute underscore your plus lands unique mechanism of action and potential for broad utility across the AML spectrum.

我們與 MD 安德森、國家癌症研究所和丹娜法伯癌症研究所的重要合作夥伴關係強調了您的優勢獨特的作用機制以及在整個 AML 譜系中廣泛應用的潛力。

Now turning to our finances. Our disciplined approach, focusing on targeted investments provides a current cash runway through year end 2024. This positions the company to be financed through our upcoming clinical milestones, data readout and potential NDA submission.

現在轉向我們的財務。我們採取嚴格的方法，專注於有針對性的投資，為 2024 年底提供了當前的現金跑道。這使得公司能夠透過即將到來的臨床里程碑、數據讀出和潛在的 NDA 提交獲得資金。

On today's call, I'm happy to be joined by our CFO, Brian Hahn, CMO, Dr. Ed rock, and our CCO. Bruce Johnson.

我很高興邀請我們的財務長 Brian Hahn、首席行銷長、Ed rock 博士以及我們的 CCO 參加今天的電話會議。布魯斯·約翰遜。

I'll now pass it over to Ed to share more details on our ongoing trial.

現在我將把它交給 Ed，分享我們正在進行的試驗的更多細節。

Thanks, Ruth, and thank you to all on the line for joining us today. As a reminder, in June 2023, the FDA cleared the addition of an optional time-based primary analysis to our Phase 3 randomized trial uproleselan in relapsed and refractory AML. This trial enrolled 388 patients and has a primary endpoint of overall survival. Survival events have continued to slow over time, so we will proceed with a time-based analysis after a data cutoff at the end of this month. We look forward to reporting top line results in Q2. As Harout mentioned, median follow-up for patients remaining on study will be over three years at time of analysis, remarkable in a trial of therapy for relapsed and refractory AML.

謝謝露絲，也感謝所有在線的人今天加入我們。提醒一下，2023 年 6 月，FDA 批准在我們針對復發性和難治性 AML 的 3 期隨機試驗 uproleselan 中添加可選的基於時間的初步分析。該試驗招募了 388 名患者，主要終點是總存活期。隨著時間的推移，生存事件繼續放緩，因此我們將在本月底數據截止後繼續進行基於時間的分析。我們期待在第二季報告營收結果。正如 Harout 所提到的，在分析時，仍在研究中的患者的中位追蹤時間將超過三年，這在復發性和難治性 AML 的治療試驗中是顯著的。

Also, the majority of surviving study patients received hematopoietic cell transplantation and at data cutoff a large majority of these patients will be at least two years post transplant. That's a notable milestone because after two years post transplant disease relapse becomes infrequent. Thus these Phase 3 clinical trial data are clinically mature and support performance of time-based primary analysis next quarter. Our trial is testing two hypotheses.

此外，大多數倖存的研究患者接受了造血細胞移植，並且在數據截止時，這些患者中的絕大多數將在移植後至少兩年。這是一個值得注意的里程碑，因為移植後兩年後疾病復發變得很少見。因此，這些 3 期臨床試驗數據在臨床上已經成熟，並支持下季度基於時間的初步分析的表現。我們的試驗正在測試兩個假設。

First, adjunctive use progressively and leads to deeper more durable measurable residual disease, negative responses to therapy. And second, these deeper responses and reduced gastrointestinal toxicity enable more patients to get to and through potentially curative hematopoietic cell transplantation rather than target a specific gene mutation, uproleselan and is designed to be agnostic to cytogenetics gene mutation profile and backbone therapy, consistent with its modular structure that mimics a natural complex carbohydrate uproleselan demonstrates an unremarkable toxicity profiles and profile and trials conducted to date.

首先，輔助治療的逐步使用會導致更深、更持久的可測量殘留疾病，以及對治療的負面反應。其次，這些更深層的反應和減少的胃腸道毒性使更多的患者能夠獲得併通過潛在的治愈性造血細胞移植，而不是針對特定的基因突變，uproleselan，並且被設計為與細胞遺傳學基因突變譜和骨幹療法無關，與其一致模仿天然複合碳水化合物uproleselan的模組化結構表現出不顯著的毒性特徵和迄今為止進行的試驗。

So we see potential for broad uproleselan and utility in combination with diverse other AML treatments across lines of therapy. Correspondingly, the uproleselan potential outside of relapsed and refractory AML is under study in multiple ongoing investigator initiated trials across AML sub-types in lines of therapy. The largest of these trials is an adaptive NCI sponsored Phase 2/3 trial conducted by the Alliance for Clinical Trials in Oncology. This NCI alliance study is testing uproleselan in newly diagnosed older patients with AML who are fit for intensive chemotherapy. The Phase 2 portion has a primary endpoint of event-free survival or EFS and completed enrollment of 267 patients in December 2021.

因此，我們看到了廣泛的 uproleselan 的潛力以及與多種其他 AML 治療跨線治療相結合的實用性。相應地，多個正在進行的研究者發起的跨 AML 亞型治療線的試驗正在研究 uproleselan 在復發性和難治性 AML 之外的潛力。其中最大的試驗是由腫瘤學臨床試驗聯盟進行的適應性 NCI 贊助的 2/3 期試驗。這項 NCI 聯盟研究正在新診斷的適合接受強化化療的老年 AML 患者中測試 uproleselan。2 期部分的主要終點是無事件存活期或 EFS，並於 2021 年 12 月完成了 267 名患者的入組。

Just this month, NCI confirmed that the Phase 2 EFS event trigger has not yet been reached this trial was designed to show median EFS prolongation from 7 to 11 months, hence was expected to reach a Phase 2 event trigger in 2022. We look forward to sharing trial results when available. As part of our collaboration the NCI also supports an ongoing Children's Oncology Group Phase 1 study conducted by COGS, pediatric early-phase clinical trial network. This dose escalation trial which is part of the initial pediatric study plan agreed on with the FDA and EMA assesses safety, pharmacokinetics and preliminary clinical activity of uproleselan plus chemotherapy in pediatric patients with relapsed or refractory AML.

就在本月，NCI 確認尚未達到第 2 階段 EFS 事件觸發點，該試驗旨在顯示中位 EFS 延長從 7 個月到 11 個月，因此預計將在 2022 年達到第 2 階段事件觸發點。我們期待分享可用的試驗結果。作為我們合作的一部分，NCI 還支持兒科早期臨床試驗網絡 COGS 正在進行的兒童腫瘤學組一期研究。這項劑量遞增試驗是 FDA 和 EMA 商定的初步兒科研究計劃的一部分，旨在評估 uproleselan 聯合化療治療復發或難治性 AML 兒科患者的安全性、藥物動力學和初步臨床活性。

Enrollment in this study is ongoing after first patient in occurred last October. Additional ongoing investigator initiated trials continue to evaluate uproleselan and combinations in AML These trials include uproleselan combinations with the conditioning regimen in patients up to 39 years old undergoing transplantation as well as with Phase 1 cytarabine and cladribine in elderly patients with frontline AML.

自去年 10 月出現第一名患者後，這項研究的招募工作仍在繼續。其他正在進行的研究者發起的試驗繼續評估AML 中的uproleselan 和組合。胞苷和克拉屈濱。

In addition, uproleselan in combination with low-dose uproleselan in patients with treated and secondary AML was recently updated at the 2023 ASH meeting. In this notoriously difficult to treat population, all of whom had adverse cytogenetics and were previously treated with hypomethylating agent. Cytarabine and cladribine uproleselan led to marrow blast reduction 72% of 18 evaluable patients. The authors concluded that this combination provides safe approach to and disease control in preparation for potential hematopoietic cell transplantation reated with a hypomethylating agent, Cladribine cytarabine and Neupro vessel and led to marrow blast.

此外，最近在 2023 年 ASH 會議上更新了烏普羅塞蘭與低劑量烏普羅塞蘭聯合用於治療和繼發性 AML 患者的情況。在這個眾所周知的難以治療的人群中，所有這些人都有不良的細胞遺傳學，並且之前都接受過低甲基化劑治療。阿糖胞苷和克拉屈濱烏普羅塞蘭導致 18 名可評估患者中 72% 的骨髓原始細胞減少。作者的結論是，這種組合為與低甲基化劑、克拉屈濱阿糖胞苷和Neupro 血管相關的潛在造血細胞移植做準備提供了安全的方法和疾病控制，並導致骨髓母細胞。

In summary, we believe uproleslan has broad potential utility across AML by targeting a novel form of chemo resistance from AML, cell binding and bone marrow uproleselan favorable safety profile makes it a good candidate for combinations with other AML therapies.

總之，我們相信 uproleslan 透過針對 AML 的一種新型化療抗藥性，在 AML 中具有廣泛的潛在用途，細胞結合和骨髓 uproleslan 良好的安全性使其成為與其他 AML 療法組合的良好候選者。

Finally, both of the two large ongoing randomized trials have seen slow event accumulation and that fact highlights potential for uproleselan to become a valuable addition to diverse existing AML therapies beyond uproleselan we recently completed our Phase 1a single-ascending dose trial of subcutaneous GMI-1687, we will evaluate this second-generation E-selectin antagonist as an outpatient self-administered subcutaneous therapy to potentially alleviate sickle cell basal occlusive events events at time of pain onset.

最後，兩項正在進行的大型隨機試驗均發現事件累積緩慢，這一事實凸顯了uproleselan 成為除uproleselan 之外的多種現有AML 療法的有價值補充的潛力，我們最近完成了皮下GMI-1687 的1a 期單劑量遞增試驗，我們將評估這種第二代 E-選擇素拮抗劑作為門診患者自行皮下治療的方式，以潛在緩解疼痛發作時的鐮狀細胞基底閉塞事件。

In addition to benefit from pain control such a point of care therapy may also reduce patient emergency room visits and hospitalizations, Phase 1a, first-in-human data in healthy volunteers, support safety and fixed dose administration of subcutaneous GMI-1687 full study results will be presented at an upcoming medical meeting.

除了從疼痛控制中獲益之外，這種護理點療法還可以減少患者急診室就診和住院治療，1a 期、健康志願者的首次人體數據支持皮下GMI-1687 完整研究結果的安全性和固定劑量給藥將在即將召開的醫學會議上提出。

Also, we're pleased to announce that we've initiated a collaboration with the Sickle Cell Disease Clinical Trials Network of the American Society of Hematology research collaboration. Through this relationship, GlycoMimetics will obtain feedback from experts and people living with sickle cell disease on our GMI 1687 clinical development plan, ASH research, collaborative fosters partnerships to expedite therapeutics development, generate high-quality evidence for clinical decision making and improve outcomes for people living with sickle cell disease. We look forward to our partnership with them.

此外，我們很高興地宣布，我們已啟動與美國血液學會鐮狀細胞疾病臨床試驗網絡的合作研究合作。透過這種關係，GlycoMimetics 將獲得專家和鐮狀細胞疾病患者對我們的GMI 1687 臨床開發計劃、ASH 研究、合作培育夥伴關係的反饋，以加快治療方法的開發，為臨床決策提供高品質的證據並改善人們的治療結果患有鐮狀細胞疾病。我們期待與他們的合作。

Now I'll turn it over to Bruce to discuss the potential commercial opportunity pending positive results of our Phase 3 trial.

現在我將把它交給 Bruce，討論我們第三階段試驗取得積極結果之前的潛在商業機會。

Thank you, Ed. from a commercial perspective, there are a number of key factors that could position you for uproleselan for success, if approved, as Rob mentioned earlier on the call, despite recent advancements in leukemia treatment there remains a significant unmet need in AML. Currently, this disease has the lowest survival rate in hematologic malignancies with a 5-year survival rate of around 30%. The outcomes are progressively worse for elderly AML patients who have a 15% 5-year overall survival rate and for relapse refractory AML patients who have a 10% 5-year overall survival rate.

謝謝你，艾德。從商業角度來看，正如Rob 早些時候在電話會議中提到的那樣，如果獲得批准，有許多關鍵因素可以幫助您獲得uproleselan 的成功，儘管最近在白血病治療方面取得了進展，但AML 方面仍然存在重大未滿足的需求。目前，此病是血液系統惡性腫瘤中存活率最低的疾病，5年存活率約30%。對於 5 年總存活率為 15% 的老年 AML 患者和 5 年總存活率為 10% 的複發難治性 AML 患者，結果逐漸惡化。

Additionally, the vast majority of AML patients have no actionable mutation and therefore, are not candidates for commercially available biomarker-driven therapy for relapsed and refractory AML patients in particular, outcomes remain dismal, and there's currently no standard of care regimen for patients who are eligible for intensive therapy. Thus novel new treatment options that are complementary to existing standard therapy with little to no additive toxicity and are not stick to mutation profile, cytogenetic risk and treatment backbone are desperately needed.

此外，絕大多數AML 患者沒有可操作的突變，因此不是商業上可用的生物標記驅動療法的候選者，特別是針對複發和難治性AML 患者，結果仍然令人沮喪，並且目前對於患有以下疾病的患者沒有標準的照護方案適合接受強化治療。因此，迫切需要新的治療方案，這些方案是對現有標準療法的補充，幾乎沒有或沒有附加毒性，並且不拘泥於突變譜、細胞遺傳學風險和治療骨幹。

Today Hematopoietic cell transplantation remains the only treatment option with curative potential. It has become increasingly clear that MRD-negative status prior to hematopoietic cell transplantation is a strong predictor of lower relapse rates and longer term survival post transplant. Therefore, we have designed you for less on as an adjunct to standard therapy with the goal of achieving deeper, more durable MRD negative remissions without additive toxicity, delivering more AML patients to and through a potentially curative hematopoietic cell transplantation.

如今，造血細胞移植仍然是唯一具有治癒潛力的治療選擇。越來越清楚的是，造血細胞移植前的 MRD 陰性狀態是較低復發率和移植後長期存活的強烈預測因子。因此，我們為您設計了作為標準治療的輔助手段，目標是在沒有附加毒性的情況下實現更深入、更持久的 MRD 陰性緩解，從而為更多的 AML 患者提供潛在治癒性造血細胞移植。

Uproleselan has an unremarkable toxicity profile with no known drug-drug interactions, no premedication, no dose-limiting toxicity, no QT prolongation or differentiation syndrome. It has been developed to be administered as a simple 20 minute IV infusion. We believe these features will provide a strong market advantage and potentially allow us to rapidly establish uproleselan as an important component of standard therapy across a variety of AML subtypes and lines of therapy. We have been building focused market access strategies that complement our medical affairs capabilities, external partnerships and teams to be ready to launch for uproleselan should our pivotal study readout positive.

Uproleselan 具有不顯著的毒性特徵，沒有已知的藥物間交互作用，無需術前用藥，無劑量限制性毒性，無 QT 延長或分化症候群。它已被開發為簡單的 20 分鐘靜脈輸注給藥方式。我們相信這些功能將提供強大的市場優勢，並有可能使我們能夠迅速將 uproleselan 確立為各種 AML 亞型和治療系列的標準治療的重要組成部分。我們一直在製定有針對性的市場准入策略，以補充我們的醫療事務能力、外部合作夥伴關係和團隊，以便在我們的關鍵研究結果積極的情況下準備啟動 uproleselan。

We are fortunate to have a critical mass of team members with long-term connectivity with the hem onc community with multiple successful launch experiences, including in AML. According to estimates from the American Cancer Society in 2024, there will be more than 20,000 new cases of AML and more than 11,000 people will die from disease relapse and unresponsiveness to standard therapy remain a significant problem with relapse rates of 50% to 60% after initial treatment. We estimate that the relapse and refractory addressable market is a growing population with more than 8,000 patients per year and an addressable market opportunity of $650 million to $850 million in the US alone. With its unique and differentiated profile, we believe uproleselan can become an important adjunct to standard AML therapy with the opportunity to be developed for future expansion into other settings, including frontline, given the potential to access a large and growing share of the over $4 billion US market opportunity across the AML treatment continuum.

我們很幸運，擁有大量與 hem onc 社群保持長期聯繫的團隊成員，擁有多次成功的發布經驗（包括在 AML 領域）。根據美國癌症協會估計，2024年將有超過20,000例新發AML病例，超過11,000人將因疾病復發而死亡，而對標準治療無反應仍然是一個重大問題，術後復發率高達50%至60%初步治療。我們估計，復發和難治性潛在市場的人口不斷增長，每年有超過 8,000 名患者，僅在美國就有 6.5 億至 8.5 億美元的潛在市場機會。憑藉其獨特和差異化的特點，我們相信uproleselan 可以成為標準AML 治療的重要輔助手段，並有機會在未來擴展到其他環境（包括一線治療），因為它有可能獲得超過40 億美元的巨大且不斷成長的份額美國整個 AML 治療的市場機會。

Now I'll turn it over to Brian for a review of financial results.

現在我將把它交給布萊恩來審查財務結果。

Thank you, Bruce. And as of December 31, 2023, GlycoMimetics had cash and cash equivalents of $41.8 million as compared to $47.9 million as of December 31, 2022. This increase was due to the company's ability to raise additional cash early in the year the company's research and development expenses decreased to $5.3 million for the quarter ended December 31, 2023, as compared to $5.9 million for the fourth quarter of 2022.

謝謝你，布魯斯。截至2023年12月31日，GlycoMimetics的現金及現金等價物為4,180萬美元，而截至2022年12月31日為4,790萬美元。這一增長是由於該公司有能力在年初籌集額外現金，該公司截至 2023 年 12 月 31 日的季度的研發費用減少至 530 萬美元，而 2022 年第四季度為 590 萬美元。

Research and development expenses for year ended December 31, 2023 decreased to $20.1 million as compared to $28.4 million in the prior year. These decreases were due to lower clinical development expenses related to our ongoing global Phase 3 clinical trial of uproleselan individuals with relapsed refractory AML and decreased manufacturing costs due to completion of engineering and validation batches for uproleselan partially offset with the completion of the Phase 1 clinical trial for GMI-1687.

截至2023年12月31日止年度的研發費用從上一年的2,840萬美元減少至2,010萬美元。這些減少是由於與我們正在進行的複發難治性AML 個體的uproleselan 全球3 期臨床試驗相關的臨床開發費用較低，以及由於uproleselan 工程和驗證批次的完成而降低的製造成本，部分抵消了1期臨床試驗的完成對於 GMI-1687。

The company's general administrative expenses decreased to $4.3 million for the quarter ended December 31, 2023, as compared to $4.7 million for the fourth quarter of 2022.

截至2023年12月31日的季度，該公司的一般管理費用減少至430萬美元，而2022年第四季為470萬美元。

General and Administrative expenses for the year ended December 31, 2023 increased to $19.2 million as compared to $19.1 million in the prior year. These increases were due to higher personnel-related expenses, offset by a decrease in external consulting expenses.

截至 2023 年 12 月 31 日止年度的一般及行政費用增加至 1,920 萬美元，而前一年為 1,910 萬美元。這些增長是由於人事相關費用增加，但被外部諮詢費用減少所抵消。

I'd now like to turn the call back to Harout.

我現在想把電話轉回哈魯特。

Thank you, Brian. In closing, it has been a long road and we now have reached a very exciting time for our company. We are focused on the upcoming top line results from our Phase 3 study of restaurants in relapse and refractory AML. We continue to work on our commercial readiness and are prepared to transition into a commercial stage company pending positive results I'd now like to open the lines to Q&A.

謝謝你，布萊恩。最後，這是一條漫長的道路，現在我們公司已經到達了一個非常令人興奮的時刻。我們專注於針對複發性和難治性 AML 餐廳的第三階段研究即將發布的重要結果。我們將繼續努力做好商業準備，並準備轉型為商業階段的公司，等待積極的結果。

Operator?

操作員？

Thank you.

謝謝。

(Operator Instructions)

（操作員說明）

Tony Bancroft with TD Cowen.

托尼·班克羅夫特和 TD Cowen。

Hey, good morning. So my first question is weather. You believe that Frontline results could be available in time to potentially be included together with the relapsed refractory data and a filing or what's the plan for that? And then next year, if the Phase 3 that you're running is successful. Can you describe how you think Neupro will be used initially and how that could expand over time, which patients are the low-hanging fruit because it doesn't include those with mutations on FIT or will those be added over time?

嗨，早安。所以我的第一個問題是天氣。您認為 Frontline 結果可以及時提供，並有可能與復發難治性資料和歸檔一起包含在內，或者有什麼計劃？然後明年，如果您正在運行的第三階段取得成功。您能否描述一下您認為Neupro 最初將如何使用以及如何隨著時間的推移而擴展，哪些患者是容易實現的目標，因為它不包括那些在FIT 上發生突變的患者，或者這些患者會隨著時間的推移而增加？

Thank you, Tara. Good morning. Maybe I'll turn it over to Bruce to address the second question about the potential sequence a boost. And then I'll take the first question.

謝謝你，塔拉。早安.也許我會把它交給布魯斯來解決關於潛在序列提升的第二個問題。然後我將回答第一個問題。

Sure, and thank you for the question. And I think initially, assuming positive results from the relapsed-refractory pivotal trial, we see you uproleslan quickly being established as an adjunct to standard of care with patients receiving intensive chemotherapy. We know there are a number of large volume, AML centers of excellence that treat patients with intensive therapy, and those would include patients with mutations. Remember, this is a therapy that is essentially agnostic to mutational profiles, cytogenetic profile and treatment backbone. So we envision broad utilization initially with patients who are fit for intensive therapy. Beyond that, of course, we have ongoing trials, ISTs evaluating the unfit population, and we'll wait for further data to readout on those.

當然，謝謝你的提問。我認為，最初，假設復發難治性關鍵試驗取得積極結果，我們會看到 uproleslan 很快就被確立為接受強化化療患者的標準護理的輔助手段。我們知道有許多大型的 AML 卓越中心對患者進行強化治療，其中包括攜帶突變的患者。請記住，這種療法本質上與突變譜、細胞遺傳學譜和治療主幹無關。因此，我們預計最初會在適合強化治療的患者中廣泛使用。當然，除此之外，我們還有正在進行的試驗，IST 正在評估不適合人群，我們將等待進一步的數據讀出。

Thank you, Bruce.

謝謝你，布魯斯。

And regarding your first question, tariff or the regulatory pathway with NCIL. for frontline trial. So as you just heard, we've iterated that we've had conversations with the NCI and they have confirmed that they have not reached the EFS trigger yet, which is getting quite unusual given the last patient in that trial was in December 2021 with an EFS trigger rather than an overall survival trigger, which is our case. So we kind of have to wait for that data until that happens. And of course, as you know, the Phase 2/3 adaptive trial in the frontline setting is a registrational great trial.

關於你的第一個問題，關稅或 NCIL 的監管途徑。用於前線試驗。正如您剛才聽到的，我們重申我們已經與NCI 進行了對話，他們確認尚未達到EFS 觸發點，考慮到該試驗中的最後一名患者是在2021 年12 月，這種情況變得很不尋常。所以我們必須等待數據，直到這種情況發生。當然，如您所知，前線環境中的第 2/3 階段適應性試驗是一項註冊性的偉大試驗。

So depending on the timing and depending on the data, we will have that ability to either connect them together or have them separately. We can't make that assessment now given how much delay there has been whenever that time data comes we're going to be ready to either do an SNDA or have that to be a separate and parallel path because then it really opens the market to at least double the size of the relapse refractory.

因此，根據時間和數據，我們將有能力將它們連接在一起或分開。我們現在無法做出評估，因為每當數據到來時都會有多少延遲，我們將準備好進行 SNDA 或將其作為單獨且並行的路徑，因為這樣就真正打開了市場至少是複發難治性的大小的兩倍。

I hope I addressed your costs.

我希望我已經解決了您的費用。

Yes, you did. Thank you so much.

是的，你做到了。太感謝了。

Lorraine [cavari], Capital One Securities.

洛林 [cavari]，第一資本證券。

Good morning and congrats on the progress and interesting. My question and I'm just curious in terms of, you know, the study is now time-based? And do you have a sense of what the event number is? And would you report that with the top line data? And then how quickly from a data cutoff, which will be this month, will you be able to clean it up and report the top line? I guess what I'm asking is, will you release it toward the end of 2Q? Or could it be slightly earlier?

早上好，恭喜你取得了進展並且很有趣。我的問題是，我只是好奇，你知道，這項研究現在是基於時間的嗎？您知道事件編號是多少嗎？您會用最重要的數據來報告這一點嗎？然後，從本月的資料中斷開始，您能夠多快清理資料並報告頂線？我想我要問的是，你們會在第二季末發布它嗎？或是可以稍微早一點嗎？

Yes. Thank you, Lorraine, for the question. Yes, we get asked that quite a bit as you can imagine. Yes, I mean, what we've said is we've seen a significant reduction in the number of events over multiple stages, which lead us over and '22 throughout '23 to go back to the FDA a couple of times and aligned with them on on additional path forward. Where we are now is we are seeing a further slowdown of events, but given that we've aligned as of last summer with the with the agency on a time-based analysis, given that this database is now mature from a clinical perspective, both in terms of a median follow-up of more than three years. And the fact that the vast majority of the patients who have had a transplantation have a follow-up of more than two years as well.

是的。謝謝洛林提出的問題。是的，正如你想像的那樣，我們經常被問到這個問題。是的，我的意思是，我們所說的是，我們已經看到多個階段的事件數量顯著減少，這導致我們在 22 整個 23 年間多次回到 FDA 並與他們繼續前進。我們現在的處境是，我們看到事件進一步放緩，但考慮到我們從去年夏天開始就與該機構就基於時間的分析達成一致，考慮到該數據庫現在從臨床角度來看已經成熟，中位隨訪時間超過三年。事實上，絕大多數接受移植的患者也有兩年以上的追蹤。

So that's really makes the database quite clinically mature, and we are confident with this method of triggering at. The data cutoff as you know, we've also mentioned Endo March 31. So basically in a few days and then that we got to allow the teams, the timing that it takes to do the database cleanup, you know, the database lock, the analysis that goes with it and then reporting, hopefully a positive press release in Q2. So we obviously see the number of events in the back row for our trial and we are blinded, but we do see the number of events, and we're very confident in this time-based analysis methodology.

所以這確實使資料庫在臨床上相當成熟，我們對這種觸發方法充滿信心。如您所知，數據截止日期我們也提到了遠藤 3 月 31 日。所以基本上在幾天內，然後我們必須允許團隊進行資料庫清理所需的時間，你知道，資料庫鎖定，隨之而來的分析，然後報告，希望在Q2。因此，我們顯然看到了試驗後排的事件數量，我們是盲目的，但我們確實看到了事件數量，我們對這種基於時間的分析方法非常有信心。

So stay tuned in Q2. We hopefully will have a good press release.

所以請繼續關注第二季。我們希望能有一個好的新聞稿。

Can you share just a little bit more about this recent collaboration that you have with ash RC2? Would you have any idea about the expected size of the study when it or initiate or any any other details?

可以分享一下您最近與 ash RC2 的合作嗎？您是否知道該研究的預期規模或啟動時的預期規模或任何其他細節？

Sure. Yes. No, that's not the I before I turn it to add. I'm very excited about this collaboration. As you know, sickle cell patients are still in dire need for treatment, especially with our approach. And maybe, Ed, you can further expand on on why we're excited with our collaborations.

當然。是的。不，那不是我將其添加之前的 I。我對這次合作感到非常興奮。如您所知，鐮狀細胞疾病患者仍然迫切需要治療，尤其是採用我們的方法。Ed，也許您可以進一步闡述為什麼我們對我們的合作感到興奮。

Yes. The ASH research collaborative partners with multiple sponsors to give feedback on their study drugs in sickle cell disease, the disease indication that we are going to develop, which is as a point of care our method to alleviate sickle cell basal occlusive events is unprecedented, and we will appreciate getting their expert feedback votes from their investigators internally within the ASH research collaborators, collaborative as well as from their patient forum on our clinical development plans so that we ensure that we're sort of keeping the patient's perspective in mind first and tapping into the expertise of leaders in this field.

是的。ASH 研究與多個贊助商合作，對他們的鐮狀細胞病研究藥物提供反饋，我們將要開發這種疾病指示，作為護理點，我們減輕鐮狀細胞基底閉塞事件的方法是前所未有的，並且我們將不勝感激地從ASH 研究合作者內部的研究人員、合作者以及他們的患者論壇獲得對我們臨床開發計劃的專家反饋投票，以便我們確保我們首先牢記患者的觀點並利用了解該領域領導者的專業知識。

Yes, this is very exciting for us. To be honest. I mean, the fact that we know that this unmet medical need, and we know this is a disease area where enrollment is difficult, enrollment takes time. And if you don't do it right from the beginning with a good collaboration, it can it can lead to unfortunate outcomes from a concept of a clinical trial perspective, we've learned that the hard way with our previous generation assets. And as you know, if we had stayed true to the original design, having patients be exposed to our previous generation. Within the first 26 hours, there was a statistically significant benefit as we reported in our post hoc and block last year. So this time we really want to make sure we're working hand in hand with, you know, with people who are very much involved in the sickle cell community, be it on the patient level be it on the investigators level so that we're working together in tandem to co-create what would endpoints look like, which centers with we go so that we really are able to deliver a clinical trial that not only looks good on paper, but we can actually get it done. So I'm very excited about this collaboration and hopefully we will report on progress in months to come.

是的，這對我們來說非常令人興奮。說實話。我的意思是，事實上我們知道這種未滿足的醫療需求，我們知道這是一個很難入組的疾病領域，入組需要時間。如果你沒有從一開始就進行良好的合作，從臨床試驗的角度來看，它可能會導致不幸的結果，我們已經從上一代資產的慘痛教訓中了解到這一點。如您所知，如果我們忠於最初的設計，讓患者接觸到我們的上一代產品。正如我們去年在事後和區塊中報告的那樣，在最初的 26 小時內，出現了統計上顯著的好處。所以這次我們真的想確保我們與那些積極參與鐮狀細胞社區的人們攜手合作，無論是在患者層面還是在研究人員層面，這樣我們就可以「我們齊心協力，共同創造終點是什麼樣子，以我們為中心，以便我們真正能夠提供不僅在紙上看起來不錯，而且實際上可以完成的臨床試驗。因此，我對這次合作感到非常興奮，希望我們能在未來幾個月內報告進展。

That's helpful. Okay. Sorry, one more question. And I guess just holding back to the Phase 3 study and the final one for me and assuming everything positive you plan it and submit everything to the FDA before year end? And do you have any claim far more CNC studies going to complete before?

這很有幫助。好的。抱歉，還有一個問題。我想只是保留第三階段研究和最後一項研究，並假設一切積極，你計劃它並在年底前向 FDA 提交所有內容？您是否聲稱之前還有更多的 CNC 研究要完成？

Yes. I mean, as you know, this trial has been taking much longer than than it's supposed to do. So we've been really cleaning a lot of the -- the what's needed being or the data side, but also on the clin pharm.

是的。我的意思是，正如你所知，這次審判花費的時間比預期的要長得多。因此，我們確實清理了很多需要的東西或數據方面，而且還清理了臨床製藥方面。

Regarding clinical pharmacology in agreement with the FDA exposure response analysis and exposure toxicity analysis as well as population PK analysis are included in our Phase three trial in our program. This will accommodate FDA expectations and ensure that we have appropriate information for the product label to direct safe and effective use of the drug.

關於臨床藥理學，與 FDA 一致的暴露反應分析和暴露毒性分析以及群體 PK 分析都包含在我們的三期試驗中。這將滿足 FDA 的期望，並確保我們擁有產品標籤的適當訊息，以指導藥物的安全有效使用。

Okay. Thank you.

好的。謝謝。

(Operator Instructions)

（操作員說明）

Ed White, H.C. Wainwright.

懷特，H.C.溫賴特。

Thanks for taking my question. And perhaps I could just start with 1687 this collaboration. Are there any financial stipulations in this? Does it save you money somehow? And then just if you can review your strategies for development this collaboration, you're going to go it alone. Will you be looking for you? Will you be looking for a partner to further development?

感謝您提出我的問題。也許我可以從 1687 開始這次合作。這裡面有什麼財務規定嗎？它能以某種方式幫你省錢嗎？然後，只要您能夠審查您的合作發展策略，您就會單幹。會來找你嗎？您會尋找合作夥伴以進一步發展嗎？

Yes, thank you, Ed. Good to hear your voice?

是的，謝謝你，艾德。很高興聽到你的聲音？

Yes, of course, I mean, any collaboration for it to be effective. We've got to make sure that we're compensating people's time and effort. So there is a financial component for their efforts, it's modest, but it's there.

是的，當然，我的意思是任何有效的合作。我們必須確保補償人們的時間和精力。因此，他們的努力有一個財務成分，雖然不大，但確實存在。

And regarding your second part of the question, are we going to do it alone or not?

關於問題的第二部分，我們是否要單獨完成？

I mean, that's really an open conversation.

我的意思是，這確實是一次開放的對話。

What we would know is regardless if we're doing it alone or not, we want to advance 1687, and we want to make sure that we are learning more before we advance it and move forward into a full-on clinical development program. We want to make sure that we are very in tune with the patient voice. We're very much in tune with developing endpoints that can be delivered by physicians in a clinical trial, setting it, but also it's relevant for the patient.

我們所知道的是，無論我們是否單獨進行，我們都希望推進 1687，並且我們希望確保在推進它並進入全面的臨床開發計劃之前我們能學到更多東西。我們希望確保我們與患者的聲音非常一致。我們非常適合開發終點，這些終點可以由醫生在臨床試驗中提供，設定它，但它也與患者相關。

So we are gathering a lot of insights and regardless of how we move forward, the execution of those insights is going to be helpful anyway. So for us, this is a no-regret move with a very credible group that really has aligned with us on that, that would be the sickle cell patient outcome. So that's why we're very pleased with our collaboration with them. And then those highlights will be used in due course and a clinical developments.

因此，我們正在收集大量見解，無論我們如何前進，這些見解的執行都會有所幫助。因此，對我們來說，這是一個無悔的舉動，與一個非常可信的團體合作，該團體在鐮狀細胞病患者的治療結果上確實與我們保持一致。這就是為什麼我們對與他們的合作感到非常滿意。然後這些亮點將在適當的時候用於臨床開發。

Okay. Thanks, Haroute. And then my other question on Insulation is just can you give us your thoughts in your strategy for Europe, which is something I really haven't discussed all that much in the past. But since you're getting closer to two potential launch in the US at the start, it's relevant to start thinking about that and get your thoughts on that?

好的。謝謝，哈魯特。然後，我關於絕緣的另一個問題是，您能否向我們介紹您對歐洲戰略的想法，這是我過去確實沒有討論太多的問題。但由於您一開始就距離在美國推出兩款產品越來越近，因此有必要開始考慮這一點並了解您的想法嗎？

Yes. No, absolutely. And then yes, those plans are ongoing. They're underway. Our plans are not just to work with the FDA, but also from a European perspective, we haven't guided on the European side, but the work is ongoing. As you know, our clinical trial, our Phase 3 is half US and half globally, including many sites in Europe. So we have patients over there. We have medical experts who are are exposed to your uproleslan and how to use it. And of course, we're going to be working with the European agencies as well in due time. So the first focus is on FDA, but then we should be turning our attention to Europe as well. So that's also underway.

是的。不，絕對是。是的，這些計劃正在進行中。他們正在進行中。我們的計劃不僅僅是與 FDA 合作，而且從歐洲的角度來看，我們還沒有在歐洲方面進行指導，但工作正在進行中。如你所知，我們的臨床試驗，我們的第三階段是一半在美國，一半在全球，包括歐洲的許多地點。所以我們那裡有病人。我們的醫學專家了解您的 uproleslan 以及如何使用它。當然，我們也將在適當的時候與歐洲機構合作。因此，我們首先關注的是 FDA，但隨後我們也應該將注意力轉向歐洲。所以這也在進行中。

Okay, great.

好的，太好了。

Thanks for taking my questions.

感謝您回答我的問題。

Thank you.

謝謝。

And I'm showing no further questions at this time. I'd like to turn the call back over to Herbert for any closing remark.

目前我不會再提出任何問題。我想將電話轉回給赫伯特，讓他發表結束語。

Thank you, operator, and thank you to everyone for joining our call today, and we look forward to keeping you updated on GlycoMimetics and sharing top line results in Q2 Thank you.

謝謝您，操作員，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 的最新信息並分享第二季度的頂線結果，謝謝。

This concludes today's call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連線。