本期看點(diǎn)

1. 胰高血糖素樣肽1受體（GLP-1R）和胰高血糖素受體（GCGR）雙激動(dòng)劑DA-1726的1期臨床試驗(yàn)結(jié)果亮眼，接受32 mg劑量的患者在第33天時(shí)，腰圍最多縮小3.9英寸（約9.9厘米）。

2. 基因工程改造豬肝臟EGEN-5784用于治療肝衰竭患者的臨床試驗(yàn)獲FDA許可。

藥明康德內(nèi)容團(tuán)隊(duì)整理

DA-1726：公布1期臨床試驗(yàn)數(shù)據(jù)

MetaVia公司宣布其在研療法DA-1726的1期臨床試驗(yàn)取得了積極結(jié)果。DA-1726是一種新型胃泌酸調(diào)節(jié)素（oxyntomodulin，OXM）類似物，具有GLP-1R和GCGR雙激動(dòng)劑的功能，可通過降低食欲和增加能量消耗來減輕體重。DA-1726被設(shè)計(jì)為每周皮下注射一次，擬開發(fā)用于治療肥胖和代謝功能障礙相關(guān)脂肪性肝炎（MASH）。

此次公布的結(jié)果顯示，在未進(jìn)行劑量滴定的情況下，接受32 mg劑量的患者在第26天時(shí)最大體重降幅達(dá)6.3%，平均降幅為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天時(shí)，腰圍最多縮小3.9英寸（約9.9厘米），平均縮小1.6英寸（約4.1厘米），顯示出胰高血糖素活性的強(qiáng)效信號。目前該公司正在追加試驗(yàn)組以確定最大耐受劑量。

▲接受DA-1726治療26天時(shí)患者的平均體重百分比變化（圖片來源：參考資料[1]）

EGEN-5784：IND申請獲得FDA許可

eGenesis和OrganOx公司宣布，美國FDA已批準(zhǔn)EGEN-5784的IND申請。EGEN-5784是一種適用于人體的基因工程改造豬肝臟，與OrganOx的體外肝臟交叉循環(huán)（ELC）系統(tǒng)聯(lián)用，用于治療重癥監(jiān)護(hù)環(huán)境中慢加急性肝衰竭（acute-on-chronic liver failure，ACLF）患者的肝功能失代償。

2024年11月，OrganOx與eGenesis簽署了一項(xiàng)獨(dú)家臨床共同開發(fā)協(xié)議，以推進(jìn)這一潛在的救命技術(shù)，該技術(shù)面向因急性或慢加急性肝衰竭住院的患者，他們現(xiàn)有治療選擇有限，且短期死亡率高達(dá)50%。eGenesis的基因工程改造豬肝聯(lián)合OrganOx的ELC系統(tǒng)，可以支持患者的肝臟功能，促使患者原生肝臟的恢復(fù)，或?yàn)榛颊郀幦∽銐驎r(shí)間接受肝臟移植。這項(xiàng)1期試驗(yàn)將招募多達(dá)20例不適合移植的ACLF及肝性腦?。ā?級）患者。

TGN-S11：公布1期臨床試驗(yàn)的新數(shù)據(jù)

Toragen公司公布了其人乳頭瘤病毒（HPV）E5癌基因蛋白小分子抑制劑TGN-S11在HPV相關(guān)癌癥患者中的1期臨床試驗(yàn)數(shù)據(jù)。研究結(jié)果顯示，TGN-S11單藥或與免疫檢查點(diǎn)抑制劑（ICI）帕博利珠單抗（pembrolizumab）聯(lián)用的安全性良好，沒有被認(rèn)為與TGN-S11相關(guān)的嚴(yán)重不良事件。此外，53%接受至少2個(gè)月治療的患者表現(xiàn)出藥物活性。基于該結(jié)果，公司將推動(dòng)其第二代E5癌基因蛋白抑制劑TGN-S15進(jìn)入臨床，該候選療法在臨床前研究中顯示出更高的療效以及更少的副作用。

ATX-295：1/2期臨床試驗(yàn)完成首例患者給藥

Accent Therapeutics公布宣布，其潛在“best-in-class”口服KIF18A抑制劑ATX-295的首次人體1/2期臨床試驗(yàn)已完成首例患者給藥。此外，ATX-295還獲得美國FDA授予的快速通道資格，用于治療晚期/轉(zhuǎn)移性鉑類耐藥或難治性卵巢癌成人患者。

ATX-295是有絲分裂驅(qū)動(dòng)蛋白KIF18A的選擇性抑制劑，該蛋白在染色體不穩(wěn)定腫瘤的細(xì)胞分裂中起關(guān)鍵作用，但在健康細(xì)胞中非必需。此前，Accent公司已證明，其新型、強(qiáng)效、選擇性小分子KIF18A抑制劑在臨床前模型（包括高級別漿液性卵巢癌和三陰性乳腺癌）中顯示出選擇性劑量依賴性腫瘤生長抑制作用，支持其進(jìn)入臨床。

Iadademstat：1/2期聯(lián)合試驗(yàn)完成首例患者給藥

Oryzon Genomics公司宣布，其候選療法iadademstat聯(lián)合ICI一線治療廣泛期小細(xì)胞肺癌（SCLC）的1/2期臨床試驗(yàn)已完成首例患者給藥。Iadademstat是一種口服小分子，可作為表觀遺傳酶LSD1的高選擇性抑制劑，已在血液腫瘤中展現(xiàn)出強(qiáng)大的作用。除了血液癌，iadademstat聯(lián)合治療還在一些實(shí)體瘤中展現(xiàn)初步活性。此前，該療法已在美國獲得了用于治療SCLC的孤兒藥資格，在美國和歐盟都獲得了治療急性髓系白血?。ˋML）的孤兒藥資格。

GS-6791/NX-0479：IND申請獲得FDA許可

Nurix Therapeutics公司宣布，美國FDA已批準(zhǔn)其IRAK4降解劑GS-6791/NX-0479的IND申請，該公司預(yù)計(jì)將于2025年第二季度啟動(dòng)1期臨床試驗(yàn)。GS-6791是一種強(qiáng)效、選擇性、口服IRAK4降解劑，靶向IRAK4蛋白激酶的支架和激酶功能，能夠阻斷toll樣受體（TLR）和促炎性IL1細(xì)胞因子受體家族（IL1Rs）下游的炎癥反應(yīng)。GS-6791降解IRAK4在治療類風(fēng)濕關(guān)節(jié)炎（RA）和其他炎癥性疾病的治療中具有潛在的應(yīng)用價(jià)值。Nurix公司的合作伙伴吉利德科學(xué)（Gilead Sciences）于2023年獲得了該項(xiàng)目的，并負(fù)責(zé)其臨床開發(fā)。

參考資料（可上下滑動(dòng)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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