Pociredir

本期看点： 1. 抗半乳糖凝集素-9（galectin-9）单克隆抗体LYT-200用于治疗复发/难治性急性髓系白血病（AML）和高风险骨髓增生异常综合征（MDS），在一项早期临床试验中联合标准疗法，使患者的初步总生存期（OS）较同类患者延长近10个月。 2. 新型在研变构型BCR-ABL1抑制剂TERN-701在既往接受过治疗的慢性髓系白血病（CML）患者中取得令人鼓舞的1期临床试验数据，75%接受剂量＞320 mg/天的患者在24周内达到主要分子学缓解（MMR）。 3. 创新BTK降解剂bexobrutideg（NX-5948）用于治疗复发或难治性慢性淋巴细胞白血病（CLL）和小淋巴细胞淋巴瘤（SLL），早期临床试验数据积极，患者的总缓解率（ORR）达到83%。 LYT-200：公布1b期临床试验的初步数据 Gallop Oncology公司公布了其在研药物LYT-200在1b期临床试验中的初步顶线数据。LYT-200是一种潜在“first-in-class”的抗半乳糖凝集素-9单克隆抗体，正在被评估用于治疗复发/难治性AML和高风险MDS患者。 该研究纳入了既往接受过多种治疗的晚期患者，旨在评估LYT-200作为单药或联合标准疗法的疗效与安全性。结果显示，LYT-200在推荐的2期剂量下表现出良好的耐受性和显著的抗肿瘤活性。在联合治疗组中，初步的中位OS达到13.2个月，远超此类晚期患者通常预期的＜2.5个月的生存期。此外，LYT-200在携带高风险基因突变的患者中也观察到治疗应答，提示其可能具有广泛的适用人群。 TERN-701：公布1期临床试验数据 Terns Pharmaceuticals公司宣布，在正在进行的CARDINAL临床试验中，其新型在研变构型BCR-ABL1抑制剂TERN-701在既往接受过治疗的CML患者中展现出令人鼓舞的疗效和安全性数据。数据显示，在所有可评估疗效的患者中，64%在24周内达到MMR；而在剂量＞320 mg/天的患者亚组中，这一比例提升至75%。此外，随着治疗时间延长，TERN-701继续保持良好的安全性和耐受性。 Bexobrutideg（NX-5948）：公布1a/1b期临床试验的新数据 Nurix Therapeutics公司公布了其开发的创新BTK降解剂bexobrutideg，用于治疗复发或难治性CLL和SLL的积极早期临床试验数据。数据显示，1a期临床试验中，在47名可进行疗效评估的患者中，接受bexobrutideg治疗的患者的ORR达到83%，中位无进展生存期为22.1个月，中位缓解持续时间为20.1个月。值得一提的是，这些患者此前接受过多种治疗，包括共价和/或非共价BTK抑制剂。在1b期患者队列中，早期数据显示接受剂量为600 mg的bexobrutideg治疗的患者ORR为83.3%。Bexobrutideg在所有剂量水平下耐受良好，符合先前披露的研究结果。 Pociredir：公布1b期临床试验的初步数据 Fulcrum Therapeutics公司公布了其在研疗法pociredir在镰状细胞病（SCD）患者中开展的1b期PIONEER临床试验的初步结果。Pociredir是一种靶向胚胎外胚层发育蛋白（EED）的口服小分子抑制剂。通过抑制EED，pociredir可有效下调关键的胎儿珠蛋白阻遏蛋白（包括BCL11A），从而导致胎儿血红蛋白（HbF）水平升高。 此次公布的结果显示，在第6周时，20 mg剂量组患者的平均绝对HbF水平较基线增加9.9%；其中58%（7/12）的患者HbF水平≥20%。截至2025年11月11日的数据，在完成第12周访视的患者中（n=6），20 mg组HbF平均诱导倍数＞3.75倍。此外，研究还观察到泛细胞型HbF诱导、溶血和贫血标志物改善，以及血管阻塞危象（VOC）减少的积极趋势。Pociredir总体耐受性良好，未报告与治疗相关的严重不良事件（SAEs）。 KT-621：公布1b期临床试验数据 Kymera Therapeutics公司宣布，其在研口服、潜在“first-in-class”的STAT6降解剂KT-621在BroADen特应性皮炎（AD）临床1b期试验中取得积极结果。结果显示，在100 mg和200 mg剂量组中，KT-621在皮肤和血液中分别实现了中位94%和98%的STAT6降解。同时，KT-621在血液中显著降低多项与疾病相关的2型炎症生物标志物水平，包括TARC（中位下降74%）、Eotaxin-3、IL-31和IgE，并在皮损中下调核心2型炎症及与AD相关的基因。 在临床疗效方面，KT-621在多项疾病评估终点上均表现出强劲疗效，所有患者平均湿疹面积和严重度指数（EASI）评分降低63%，瘙痒NRS峰值评分平均降低40%。对于合并哮喘的患者，中位部分呼出一氧化氮（FeNO）水平下降56%，哮喘控制获得有意义改善；合并过敏性鼻炎的患者在症状及生活质量方面也获得显著获益。安全性方面，KT-621耐受性良好，未报告严重不良事件或治疗相关不良事件，未出现结膜炎病例，生命体征、实验室检查及心电图亦未见临床相关异常。 REC-4881：公布1b/2期临床试验数据 Recursion公司宣布，其在研变构型MEK1/2抑制剂REC-4881在家族性腺瘤性息肉病（FAP）患者中开展的1b/2期TUPELO临床试验取得积极数据。自然病程分析显示，在55例未接受治疗、且符合TUPELO试验入组标准的FAP患者中，87%的患者每年息肉负荷呈增加趋势，10%保持稳定，仅有3%出现轻微减少，展现了该疾病的进行性发展特征。 此次公布的结果显示，接受REC-4881 4 mg/天治疗的患者在12周内即展现出快速临床活性：在12例可评估患者中，75%出现结肠息肉负荷减少，中位减少幅度达43%。停药12周后（研究第25周），11例可评估患者中有9例（82%）仍维持疗效，息肉负荷较基线中位减少53%。此外，40%的患者（4/10）实现Spigelman分期改善≥1分，表明上消化道疾病严重程度减轻。安全性方面，REC-4881的安全性特征与MEK1/2抑制一致，大多数治疗相关不良事件为1级或2级，未报告4级及以上的治疗相关不良事件。 参考资料： [1] Molecular Partners Presents Updated Data from Ongoing Phase 1/2a Trial of MP0533 in AML at ASH Annual Meeting. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/07/3201111/0/en/Molecular-Partners-Presents-Updated-Data-from-Ongoing-Phase-1-2a-Trial-of-MP0533-in-AML-at-ASH-Annual-Meeting.html [2] Rigel Presents Updated Data from the Ongoing Phase 1b Study Evaluating R289 in Patients with Lower-Risk MDS at the 67th ASH Annual Meeting and Exposition. Retrieved December 12, 2025, from https://www.prnewswire.com/news-releases/rigel-presents-updated-data-from-the-ongoing-phase-1b-study-evaluating-r289-in-patients-with-lower-risk-mds-at-the-67th-ash-annual-meeting-and-exposition-302634716.html [3] Beam Therapeutics Reports Updated Data from BEACON Phase 1/2 Trial of ristoglogene autogetemcel (risto-cel) Highlighting Durable, Differentiated Profile in Sickle Cell Disease (SCD) at American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/06/3201044/0/en/Beam-Therapeutics-Reports-Updated-Data-from-BEACON-Phase-1-2-Trial-of-ristoglogene-autogetemcel-risto-cel-Highlighting-Durable-Differentiated-Profile-in-Sickle-Cell-Disease-SCD-at-.html [4] Fulcrum Therapeutics Announces Positive Initial Results from the 20 mg Dose Cohort of the Phase 1b PIONEER Trial of Pociredir in Sickle Cell Disease at the 67th American Society of Hematology Annual Meeting. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/06/3201099/0/en/Fulcrum-Therapeutics-Announces-Positive-Initial-Results-from-the-20-mg-Dose-Cohort-of-the-Phase-1b-PIONEER-Trial-of-Pociredir-in-Sickle-Cell-Disease-at-the-67th-American-Society-of.html [5] TScan Therapeutics Announces Positive Updated Data from the ALLOHA™ Phase 1 Heme Trial at the 67th American Society of Hematology Annual Meeting and Exposition. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/06/3201100/0/en/TScan-Therapeutics-Announces-Positive-Updated-Data-from-the-ALLOHA-Phase-1-Heme-Trial-at-the-67th-American-Society-of-Hematology-Annual-Meeting-and-Exposition.html [6] Korean gene therapy RZ-001 reports encouraging phase 1 data in brain cancer. Retrieved December 12, 2025, from https://www.koreabiomed.com/news/articleView.html?idxno=29888 [7] Encoded Therapeutics Presents Positive Interim Efficacy Data from Initial Dose Levels of Phase 1/2 Trials Evaluating ETX101 Gene Therapy in Dravet Syndrome. Retrieved December 12, 2025, from https://encoded.com/press-releases/encoded-therapeutics-presents-positive-interim-efficacy-data-from-initial-dose-levels-of-phase-1-2-trials-evaluating-etx101-gene-therapy-in-dravet-syndrome/ [8] PureTech’s Founded Entity Gallop Oncology Announces Positive Initial Topline Data from Phase 1b Trial of LYT-200 in Relapsed/Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome. Retrieved December 12, 2025, from https://www.businesswire.com/news/home/20251205523069/en/PureTechs-Founded-Entity-Gallop-Oncology-Announces-Positive-Initial-Topline-Data-from-Phase-1b-Trial-of-LYT-200-in-RelapsedRefractory-Acute-Myeloid-Leukemia-and-High-Risk-Myelodysplastic-Syndrome [9] Kymera Therapeutics Announces Positive Results from BroADen Phase 1b Clinical Trial of KT-621, a First-in-Class, Oral STAT6 Degrader, in Patients with Moderate to Severe Atopic Dermatitis. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/08/3201397/0/en/Kymera-Therapeutics-Announces-Positive-Results-from-BroADen-Phase-1b-Clinical-Trial-of-KT-621-a-First-in-Class-Oral-STAT6-Degrader-in-Patients-with-Moderate-to-Severe-Atopic-Dermat.html [10] Assembly Biosciences Reports Positive Interim Results from Phase 1b Clinical Studies of Long-Acting Helicase-Primase Inhibitor Candidates ABI-1179 and ABI-5366 Showing Reductions in Viral Shedding Rate and Virologically Confirmed Genital Lesion Rate in Recurrent Genital Herpes. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/08/3201967/16259/en/Assembly-Biosciences-Reports-Positive-Interim-Results-from-Phase-1b-Clinical-Studies-of-Long-Acting-Helicase-Primase-Inhibitor-Candidates-ABI-1179-and-ABI-5366-Showing-Reductions-i.html [11] Terns Highlights Additional Positive Phase 1 Clinical Data Supporting TERN-701’s Best-in-Disease Potential in Relapsed/Refractory CML at the 67th ASH Annual Meeting. Retrieved December 12, 2025, from https://ir.ternspharma.com/news-releases/news-release-details/terns-highlights-additional-positive-phase-1-clinical-data [12] Corvus Pharmaceuticals Presents Final Data from Soquelitinib Phase 1/1b T Cell Lymphoma Trial. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/08/3201702/0/en/Corvus-Pharmaceuticals-Presents-Final-Data-from-Soquelitinib-Phase-1-1b-T-Cell-Lymphoma-Trial.html [13] Fate Therapeutics Presents Updated Phase 1 Clinical Data of FT819 Off-the-shelf CAR T-cell Product Candidate for Systemic Lupus Erythematosus and Preclinical Advances in Next-Generation Off-the-Shelf CAR T-cell Programs. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/08/3201474/24675/en/Fate-Therapeutics-Presents-Updated-Phase-1-Clinical-Data-of-FT819-Off-the-shelf-CAR-T-cell-Product-Candidate-for-Systemic-Lupus-Erythematosus-and-Preclinical-Advances-in-Next-Gener.html [14] Positive Phase 1b/2 Results from Ongoing REC-4881 TUPELO Trial Demonstrate Rapid and Durable Reductions in Polyp Burden in Familial Adenomatous Polyposis (FAP) at 25 Weeks. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/08/3201434/0/en/Positive-Phase-1b-2-Results-from-Ongoing-REC-4881-TUPELO-Trial-Demonstrate-Rapid-and-Durable-Reductions-in-Polyp-Burden-in-Familial-Adenomatous-Polyposis-FAP-at-25-Weeks.html [15] Star Therapeutics Presents Interim Data from Phase 1/2 Multidose Study of VGA039 in Von Willebrand Disease, Demonstrating Substantial Bleed Reductions in All Patients, at ASH Annual Meeting. Retrieved December 12, 2025, from https://www.businesswire.com/news/home/20251205981362/en/Star-Therapeutics-Presents-Interim-Data-from-Phase-12-Multidose-Study-of-VGA039-in-Von-Willebrand-Disease-Demonstrating-Substantial-Bleed-Reductions-in-All-Patients-at-ASH-Annual-Meeting  [16] Kite’s Next-Generation Bicistronic CAR T-Cell Therapies Show Encouraging Phase 1 Results in Relapsed/Refractory B-Cell Lymphoma in New Data at ASH 2025. Retrieved December 12, 2025, from https://www.businesswire.com/news/home/20251206612260/en/Kites-Next-Generation-Bicistronic-CAR-T-Cell-Therapies-Show-Encouraging-Phase-1-Results-in-RelapsedRefractory-B-Cell-Lymphoma-in-New-Data-at-ASH-2025 [17] Senti Bio Announces Updated SENTI-202 Clinical Data from Ongoing Phase 1 Trial in Relapsed or Refractory Acute Myeloid Leukemia Patients, Demonstrating Deep, MRD Negative, Durable Complete Remissions and a Favorable Safety Profile. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/09/3202225/0/en/Senti-Bio-Announces-Updated-SENTI-202-Clinical-Data-from-Ongoing-Phase-1-Trial-in-Relapsed-or-Refractory-Acute-Myeloid-Leukemia-Patients-Demonstrating-Deep-MRD-Negative-Durable-Com.html [18] ONL Therapeutics Announces Publication of Data from Phase 1b Study of Xelafaslatide, an Investigational Therapy for Geographic Atrophy, in Ophthalmology Science. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/09/3202198/0/en/ONL-Therapeutics-Announces-Publication-of-Data-from-Phase-1b-Study-of-Xelafaslatide-an-Investigational-Therapy-for-Geographic-Atrophy-in-Ophthalmology-Science.html [19] Aleta Biotherapeutics and Cancer Research UK Announce Promising Phase I/II Data from ALETA-001 Clinical Trial for Patients With Relapsed/Refractory B-Cell Malignancies Previously Treated with CD19 CAR T-Cell Therapy. Retrieved December 12, 2025, from https://www.businesswire.com/news/home/20251208038512/en/Aleta-Biotherapeutics-and-Cancer-Research-UK-Announce-Promising-Phase-III-Data-from-ALETA-001-Clinical-Trial-for-Patients-With-RelapsedRefractory-B-Cell-Malignancies-Previously-Treated-with-CD19-CAR-T-Cell-Therapy [20] Abcuro Presents Interim Phase 1 Data Evaluating Ulviprubart in Patients with T Cell Large Granular Lymphocytic Leukemia at the 67th American Society of Hematology Annual Meeting. Retrieved December 12, 2025, from https://abcuro.com/uncategorized/abcuro-presents-interim-phase-1-data-evaluating-ulviprubart-in-patients-with-t-cell-large-granular-lymphocytic-leukemia-at-the-67th-american-society-of-hematology-annual-meeting/ [21] Igyxos Biotherapeutics Announces Positive Results from Phase 1 Trial of IGX12, its First-in-Class Monoclonal Antibody for the Treatment of Male and Female Infertility. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/10/3202943/0/en/Igyxos-Biotherapeutics-Announces-Positive-Results-from-Phase-1-Trial-of-IGX12-its-First-in-Class-Monoclonal-Antibody-for-the-Treatment-of-Male-and-Female-Infertility.html [22] NovaBridge Presents Positive Ragistomig Phase 1 Dose Expansion Data at ESMO-IO. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/10/3203528/0/en/NovaBridge-Presents-Positive-Ragistomig-Phase-1-Dose-Expansion-Data-at-ESMO-IO.html [23] Enterprise Therapeutics publishes results of Phase 1 study of ETD001, a novel inhaled ENaC blocker for treatment of Cystic Fibrosis, in The Journal of Cystic Fibrosis. Retrieved December 12, 2025, from https://enterprisetherapeutics.com/enterprise-therapeutics-publishes-results-of-phase-1-study-of-etd001-a-novel-inhaled-enac-blocker-for-treatment-of-cystic-fibrosis-in-the-journal-of-cystic-fibrosis/ [24] Results from Phase 1 Multiple-Dose Study of PT00114. Retrieved December 12, 2025, from https://www.pressviewer.com/profiles/investor/NewsPrint.asp?v=6&b=2612&ID=160340&m=rl&g=1834 [25] ImmuneWalk Therapeutics Announces Positive Results from Phase 1 SAD/MAD Study of IW-601, a First-In-Class Therapeutic with Broad Potential in Inflammatory and Autoimmune Diseases. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/11/3203848/0/en/ImmuneWalk-Therapeutics-Announces-Positive-Results-from-Phase-1-SAD-MAD-Study-of-IW-601-a-First-In-Class-Therapeutic-with-Broad-Potential-in-Inflammatory-and-Autoimmune-Diseases.html [26] Corbus Pharmaceuticals Reports Results from Phase 1a Study of Oral CB1 Inverse Agonist CRB-913 for the Treatment for Obesity Demonstrating Favorable Safety Profile and Emerging Evidence of Weight Loss. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/11/3203762/0/en/Corbus-Pharmaceuticals-Reports-Results-from-Phase-1a-Study-of-Oral-CB1-Inverse-Agonist-CRB-913-for-the-Treatment-for-Obesity-Demonstrating-Favorable-Safety-Profile-and-Emerging-Evi.html [27] Tenaya Therapeutics Reports Positive Interim Data from Cohort 1 of RIDGE™-1 Phase 1b/2 Clinical Trial of TN-401 Gene Therapy for Adults with PKP2-associated ARVC. Retrieved December 12, 2025, from https://www.globenewswire.com/news-release/2025/12/11/3204284/0/en/Tenaya-Therapeutics-Reports-Positive-Interim-Data-from-Cohort-1-of-RIDGE-1-Phase-1b-2-Clinical-Trial-of-TN-401-Gene-Therapy-for-Adults-with-PKP2-associated-ARVC.html 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新