一周一次，33天腰围缩小近10厘米的多肽疗法；猪肝脏治疗肝衰竭患者的临床试验获FDA许可…… | 一周盘点

本期看点

1. 胰高血糖素样肽1受体（GLP-1R）和胰高血糖素受体（GCGR）双激动剂DA-1726的1期临床试验结果亮眼，接受32 mg剂量的患者在第33天时，腰围最多缩小3.9英寸（约9.9厘米）。

2. 基因工程改造猪肝脏EGEN-5784用于治疗肝衰竭患者的临床试验获FDA许可。

药明康德内容团队整理

DA-1726：公布1期临床试验数据

MetaVia公司宣布其在研疗法DA-1726的1期临床试验取得了积极结果。DA-1726是一种新型胃泌酸调节素（oxyntomodulin，OXM）类似物，具有GLP-1R和GCGR双激动剂的功能，可通过降低食欲和增加能量消耗来减轻体重。DA-1726被设计为每周皮下注射一次，拟开发用于治疗肥胖和代谢功能障碍相关脂肪性肝炎（MASH）。

此次公布的结果显示，在未进行剂量滴定的情况下，接受32 mg剂量的患者在第26天时最大体重降幅达6.3%，平均降幅为4.3%（p=0.0005），空腹血糖最多降低18 mg/dL，平均降低5.3 mg/dL；第33天时，腰围最多缩小3.9英寸（约9.9厘米），平均缩小1.6英寸（约4.1厘米），显示出胰高血糖素活性的强效信号。目前该公司正在追加试验组以确定最大耐受剂量。

▲接受DA-1726治疗26天时患者的平均体重百分比变化（图片来源：参考资料[1]）

EGEN-5784：IND申请获得FDA许可

eGenesis和OrganOx公司宣布，美国FDA已批准EGEN-5784的IND申请。EGEN-5784是一种适用于人体的基因工程改造猪肝脏，与OrganOx的体外肝脏交叉循环（ELC）系统联用，用于治疗重症监护环境中慢加急性肝衰竭（acute-on-chronic liver failure，ACLF）患者的肝功能失代偿。

2024年11月，OrganOx与eGenesis签署了一项独家临床共同开发协议，以推进这一潜在的救命技术，该技术面向因急性或慢加急性肝衰竭住院的患者，他们现有治疗选择有限，且短期死亡率高达50%。eGenesis的基因工程改造猪肝联合OrganOx的ELC系统，可以支持患者的肝脏功能，促使患者原生肝脏的恢复，或为患者争取足够时间接受肝脏移植。这项1期试验将招募多达20例不适合移植的ACLF及肝性脑病（≤3级）患者。

TGN-S11：公布1期临床试验的新数据

Toragen公司公布了其人乳头瘤病毒（HPV）E5癌基因蛋白小分子抑制剂TGN-S11在HPV相关癌症患者中的1期临床试验数据。研究结果显示，TGN-S11单药或与免疫检查点抑制剂（ICI）帕博利珠单抗（pembrolizumab）联用的安全性良好，没有被认为与TGN-S11相关的严重不良事件。此外，53%接受至少2个月治疗的患者表现出药物活性。基于该结果，公司将推动其第二代E5癌基因蛋白抑制剂TGN-S15进入临床，该候选疗法在临床前研究中显示出更高的疗效以及更少的副作用。

ATX-295：1/2期临床试验完成首例患者给药

Accent Therapeutics公布宣布，其潜在“best-in-class”口服KIF18A抑制剂ATX-295的首次人体1/2期临床试验已完成首例患者给药。此外，ATX-295还获得美国FDA授予的快速通道资格，用于治疗晚期/转移性铂类耐药或难治性卵巢癌成人患者。

ATX-295是有丝分裂驱动蛋白KIF18A的选择性抑制剂，该蛋白在染色体不稳定肿瘤的细胞分裂中起关键作用，但在健康细胞中非必需。此前，Accent公司已证明，其新型、强效、选择性小分子KIF18A抑制剂在临床前模型（包括高级别浆液性卵巢癌和三阴性乳腺癌）中显示出选择性剂量依赖性肿瘤生长抑制作用，支持其进入临床。

Iadademstat：1/2期联合试验完成首例患者给药

Oryzon Genomics公司宣布，其候选疗法iadademstat联合ICI一线治疗广泛期小细胞肺癌（SCLC）的1/2期临床试验已完成首例患者给药。Iadademstat是一种口服小分子，可作为表观遗传酶LSD1的高选择性抑制剂，已在血液肿瘤中展现出强大的作用。除了血液癌，iadademstat联合治疗还在一些实体瘤中展现初步活性。此前，该疗法已在美国获得了用于治疗SCLC的孤儿药资格，在美国和欧盟都获得了治疗急性髓系白血病（AML）的孤儿药资格。

GS-6791/NX-0479：IND申请获得FDA许可

Nurix Therapeutics公司宣布，美国FDA已批准其IRAK4降解剂GS-6791/NX-0479的IND申请，该公司预计将于2025年第二季度启动1期临床试验。GS-6791是一种强效、选择性、口服IRAK4降解剂，靶向IRAK4蛋白激酶的支架和激酶功能，能够阻断toll样受体（TLR）和促炎性IL1细胞因子受体家族（IL1Rs）下游的炎症反应。GS-6791降解IRAK4在治疗类风湿关节炎（RA）和其他炎症性疾病的治疗中具有潜在的应用价值。Nurix公司的合作伙伴吉利德科学（Gilead Sciences）于2023年获得了该项目的，并负责其临床开发。

参考资料（可上下滑动查看）

[1] MetaVia Announces Positive Top-Line Data From the 4-Week Phase 1 MAD Trial of DA-1726, a Novel 3:1 Ratio GLP-1 Glucagon Dual Receptor Agonist to Treat Obesity, Showing Compelling Weight Loss and Safety Effects With Potential Best-In-Class Glucose Control (GLP-1R), Waist Reduction (GCGR), and Tolerability. Retrieved April 18, 2025, from https://www.prnewswire.com/news-releases/metavia-announces-positive-top-line-data-from-the-4-week-phase-1-mad-trial-of-da-1726-a-novel-31-ratio-glp-1-glucagon-dual-receptor-agonist-to-treat-obesity-showing-compelling-weight-loss-and-safety-effects-with-potential-best--302428044.html

[2] Pheast Therapeutics Announces First Patient Treated in Phase 1 Clinical Trial of PHST001 for Patients with Advanced Solid Tumors. Retrieved April 18, 2025, from https://www.pheast.com/pheast-therapeutics-announces-first-patient-treated-in-phase-1-clinical-trial-of-phst001-for-patients-with-advanced-solid-tumors/

[3] eGenesis and OrganOx Announce U.S. FDA Clearance of IND Application for the Treatment of Patients with Acute-On-Chronic Liver Failure. Retrieved April 18, 2025, from https://www.organox.com/news/view/egenesis-and-organox-announce-u-s-fda-clearance-of-ind-application-for-the-treatment-of-patients-with-acute-on-chronic-liver-failure

[4] Accent Therapeutics Announces First Patient Dosed in Phase 1/2 Trial of Novel KIF18A Inhibitor ATX-295 and Receives FDA Fast Track Designation for Lead Assets ATX-295 and DHX9 Inhibitor ATX-559. Retrieved April 18, 2025, from https://www.prnewswire.com/news-releases/accent-therapeutics-announces-first-patient-dosed-in-phase-12-trial-of-novel-kif18a-inhibitor-atx-295-and-receives-fda-fast-track-designation-for-lead-assets-atx-295-and-dhx9-inhibitor-atx-559-302427964.html

[5] Radiance Announces First Patient Dosing in Phase 1 Clinical Trial . Retrieved April 18, 2025, from of its Next Generation ROR-1 Targeted ADC for Hematologic and Solid Malignancies. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/15/3062176/0/en/Radiance-Announces-First-Patient-Dosing-in-Phase-1-Clinical-Trial-of-its-Next-Generation-ROR-1-Targeted-ADC-for-Hematologic-and-Solid-Malignancies.html

[6] ORYZON announces first patient dosed in NCI-sponsored Phase I/II clinical trial of iadademstat plus immune checkpoint inhibitors in 1L extensive stage Small Cell Lung Cancer. Retrieved April 18, 2025, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-phase-iii-clinical-trial

[7] Toragen, Inc. Provides Update on Phase 1 Clinical Trial of TGN-S11 as Monotherapy and in Combination with Keytruda® in Patients with Stage 4 HPV-Associated Cancers. Retrieved April 18, 2025, from https://www.businesswire.com/news/home/20250415547251/en/Toragen-Inc.-Provides-Update-on-Phase-1-Clinical-Trial-of-TGN-S11-as-Monotherapy-and-in-Combination-with-Keytruda-in-Patients-with-Stage-4-HPV-Associated-Cancers

[8] Cullinan Therapeutics Receives Approval from European Medicines Agency to Initiate Phase 1 Trial of CLN-978, a Bispecific CD19 T Cell Engager Administered Subcutaneously, in Patients with Rheumatoid Arthritis. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/16/3062407/0/en/Cullinan-Therapeutics-Receives-Approval-from-European-Medicines-Agency-to-Initiate-Phase-1-Trial-of-CLN-978-a-Bispecific-CD19-T-Cell-Engager-Administered-Subcutaneously-in-Patients.html

[9] BlueRock Therapeutics announces publication in Nature of 18-month data from Phase 1 clinical trial for bemdaneprocel, an investigational cell therapy for Parkinson’s disease. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/16/3062745/0/en/BlueRock-Therapeutics-announces-publication-in-Nature-of-18-month-data-from-Phase-1-clinical-trial-for-bemdaneprocel-an-investigational-cell-therapy-for-Parkinson-s-disease.html

[10] Nurix Announces FDA Clearance of IND Application for GS-6791/NX-0479 - a Novel IRAK4 Degrader for Inflammatory Conditions. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/17/3063255/0/en/Nurix-Announces-FDA-Clearance-of-IND-Application-for-GS-6791-NX-0479-a-Novel-IRAK4-Degrader-for-Inflammatory-Conditions.html

[11] Calidi Biotherapeutics Announces FDA Clearance of IND Application for CLD-201 in Solid Tumors. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/17/3063326/0/en/Calidi-Biotherapeutics-Announces-FDA-Clearance-of-IND-Application-for-CLD-201-in-Solid-Tumors.html

[12] Verve Therapeutics Announces Positive Initial Data from the Heart-2 Phase 1b Clinical Trial of VERVE-102, an In Vivo Base Editing Medicine Targeting PCSK9. Retrieved April 18, 2025, from https://www.globenewswire.com/news-release/2025/04/14/3060774/0/en/Verve-Therapeutics-Announces-Positive-Initial-Data-from-the-Heart-2-Phase-1b-Clinical-Trial-of-VERVE-102-an-In-Vivo-Base-Editing-Medicine-Targeting-PCSK9.html

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