本期看点1. 抗体偶联药物(ADC)CX-2051在晚期结直肠癌(CRC)中取得了积极的1期临床试验结果,总缓解率(ORR)为28%,疾病控制率(DCR)达94%。2. IL-4Rα靶向单抗APG808在治疗哮喘的1b期临床试验中表现亮眼,该疗法在12周内对一种与哮喘恶化相关的2型炎症生物标志物具有强效且持续的抑制作用,有望支持其实现每两个月或更长时间一次的给药方案。3. FDA批准了Lantern Pharma公司的新型“合成致死”小分子药物LP-184的IND申请。CX-2051:公布1期临床试验的中期数据CytomX Therapeutics公布了其ADC疗法CX-2051在晚期结直肠癌(CRC)中的积极1期中期数据。CX-2051是一种条件激活型ADC,其使用的细胞毒性有效载荷是喜树碱的衍生物。喜树碱是一种拓扑异构酶-1抑制剂,这类药物已在ADC领域针对多个靶点显示出强大的临床抗癌活性。CX-2051已在包括结直肠癌在内的多个临床前模型中显示出强大的临床前活性和耐受性。截至2025年4月7日的数据,ORR为28%(5/18),其中10 mg/kg剂量组的ORR达到43%(3/7),显著高于目前三线及三线以上结直肠癌治疗药物的缓解率(通常仅有个位数的百分比)。DCR为94%(17/18),中位无进展生存期为5.8个月。截至数据截止时,18名患者中有10名仍在接受治疗。安全性方面,CX-2051的耐受性良好,未出现剂量限制性毒性(DLT),大多数治疗相关不良事件为1级或2级。APG808:公布1b期临床试验的中期数据Apogee Therapeutics公司公布了其候选单抗APG808用于治疗轻度至中度哮喘患者的1b期临床试验的积极中期数据。APG808是一种新型、皮下注射、半衰期延长的IL-4Rα靶向单抗,具有用于治疗哮喘、慢性阻塞性肺病(COPD)及其他炎症与免疫学适应症的潜力。IL-4Rα是一个已在八种2型过敏性疾病中得到临床验证的靶点。在1期临床试验中,APG808的药代动力学(PK)特征有望支持每2-3个月一次的维持治疗给药方案。此次公布的结果显示,多剂量给药APG808可使FeNO(一种与哮喘恶化相关的2型炎症生物标志物)较基线大幅下降53%,并在12周时仍维持约50%的抑制水平,显示出对哮喘的持续控制能力。APG808的优化配方和潜在“best-in-class”的PK特征,结合在12周内对FeNO的强效且持续的抑制作用,有望支持其实现每两个月或更长时间一次的给药方案,相较于目前每两周一次的标准治疗具有优势。此外,APG808整体耐受性良好,安全性特征与已有的抗IL-4Rα疗法一致。Soquelitinib:公布1期临床试验中队列1-3的数据Corvus Pharmaceuticals公司公布了其小分子白细胞介素-2诱导的T细胞激酶(ITK)抑制剂soquelitinib用于治疗中度至重度特应性皮炎的1期临床试验数据。ITK是一种主要表达于T细胞中的酶,在T细胞和自然杀伤(NK)细胞的免疫功能中起重要作用。通过抑制ITK,soquelitinib有望抑制自身免疫和炎症反应。此次公布的结果显示,所有3个队列中,soquelitinib治疗组在具有临床意义的终点湿疹面积和严重度指数较基线减少75%(EASI 75)和研究者总体评估(IGA)评分为0/1(皮肤症状清除或几乎清除)上,均显示出相较于安慰剂的显著疗效。与队列1和队列2(100 mg每天两次和200 mg每天一次,每日总剂量200 mg)相比,队列3(200 mg每天两次,每日总剂量400 mg)的缓解更早且更深。安全性方面,soquelitinib的耐受性良好,在所有队列中均未观察到DLT,也未出现具有临床意义的实验室指标异常。此外,所有队列中均未发生中断给药的情况。▲治疗第28天达到终点IGA 0/1、EASI 75的患者占比(图片来源:参考资料[1])ELVN-001:公布1期临床试验的新数据Enliven Therapeutics公司公布其小分子激酶抑制剂ELVN-001治疗慢性粒细胞白血病(CML)患者的1期临床试验的新数据。ELVN-001是一种强效、高选择性、潜在“best-in-class”的小分子激酶抑制剂,专门针对CML患者的致癌驱动因子BCR-ABL融合蛋白。ELVN-001还具有针对耐药性最强的BCR-ABL1耐药突变体T315I和其他已知耐药突变体的活性。截至2025年1月21日的数据,在36例可评估的患者中,44%(16/36)在24周时达到主要分子学缓解(MMR),其中最后一线治疗时对酪氨酸激酶抑制剂(TKI)耐药的患者中有40%(10/25)达到了MMR,曾接受asciminib或ponatinib治疗的患者中也有36%(9/25)达到MMR,包括1例携带已知asciminib耐药突变的患者。所有达到或维持MMR的患者在数据截止时仍保持缓解。在该临床试验中所纳入的患者群体此前接受过大量治疗的情况下,ELVN-001与已获批的针对BCR-ABL融合蛋白的TKI在1期试验中所观察到的MMR相比,结果依然更好。安全性方面,ELVN-001在所有剂量组中仍表现出良好的耐受性,与其选择性激酶谱一致。LP-184:IND申请获得FDA许可Lantern Pharma公司宣布,FDA已批准其抗癌新药LP-184的IND申请。LP-184将与免疫检查点抑制剂联用,针对携带KEAP1和/或STK11突变和PD-L1低表达的非小细胞肺癌(NSCLC)患者开展1b/2期临床试验。LP-184是一种新型“合成致死”小分子药物,其作用机制是在前列腺素还原酶1(PTGR1)的激活下诱导DNA双链断裂。PTGR1在KEAP1突变型肿瘤中显著过表达。临床前研究表明,LP-184对NSCLC细胞系的杀伤力与PTGR1的表达水平呈正相关。该公司专有的RADR平台驱动的计算机分析和临床前研究表明,LP-184对DNA损伤修复(DDR)缺陷型癌症特别有效,包括携带KEAP1和STK11突变的NSCLC。此外,PTGR1会在肿瘤细胞内将LP-184由前药转化为具有生物活性的细胞毒性物质,而正常组织由于PTGR1表达水平低,基本不受影响。这使得LP-184有望在具有强效抗肿瘤活性的同时降低全身毒性。值得注意的是,LP-184的作用机制不受TP53突变状态影响。该突变是导致当前多种疗法产生耐药性的常见共突变因素。参考资料(可上下滑动查看)[1] Corvus Pharmaceuticals Announces Data from Cohorts 1-3 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved May 16, 2025, from https://investor.corvuspharma.com/news-releases/news-release-details/corvus-pharmaceuticals-announces-data-cohorts-1-3-placebo[2] MaaT Pharma Announces Promising Final Data Readout for Phase 1b Evaluating MaaT033 in Amyotrophic Lateral Sclerosis (ALS). Retrieved May 16, 2025, from https://www.businesswire.com/news/home/20250511855391/en/MaaT-Pharma-Announces-Promising-Final-Data-Readout-for-Phase-1b-Evaluating-MaaT033-in-Amyotrophic-Lateral-Sclerosis-ALS[3] Cantargia announces successful Phase 1 results: PK/PD data of subcutaneously administered CAN10 confirms every 4-week dosing choice in Phase 2. Retrieved May 16, 2025, from https://cantargia.com/en/press-releases/cantargia-announces-successful-phase-1-results-pk-pd-data-of-subcutaneously-administered-can10-confirms-every-4-week-dosing-choice-in-phase-2[4] Apogee Therapeutics Announces Positive Interim Results from the Phase 1b Trial of APG808, its Novel Half-life Extended IL-4Rα Antibody, in Patients with Mild-to-Moderate Asthma. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078912/0/en/Apogee-Therapeutics-Announces-Positive-Interim-Results-from-the-Phase-1b-Trial-of-APG808-its-Novel-Half-life-Extended-IL-4R%CE%B1-Antibody-in-Patients-with-Mild-to-Moderate-Asthma.html[5] CytomX Announces Positive Interim Data From Phase 1 Dose Escalation Study of EpCAM Antibody Drug Conjugate (CX-2051) Candidate in Patients with Advanced Colorectal Cancer (CRC). Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078935/37704/en/CytomX-Announces-Positive-Interim-Data-From-Phase-1-Dose-Escalation-Study-of-EpCAM-Antibody-Drug-Conjugate-CX-2051-Candidate-in-Patients-with-Advanced-Colorectal-Cancer-CRC.html[6] MavriX Bio Announces FDA Clearance of IND Application to Initiate First-in-Human Study of Gene Therapy for Angelman Syndrome. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/mavrix-bio-announces-fda-clearance-of-ind-application-to-initiate-first-in-human-study-of-gene-therapy-for-angelman-syndrome-302451763.html[7] Ensoma Announces FDA Clearance of IND Application for First In Vivo HSC-Directed Gene Insertion Therapy. Retrieved May 16, 2025, from https://ensoma.com/press-release/ensoma-announces-fda-clearance-of-ind-application-for-first-in-vivo-hsc-directed-gene-insertion-therapy/[8] Faron Pharmaceuticals presents promising Phase 1/2 data from BEXMAB Study at MDS 2025 plenary session. Retrieved May 16, 2025, from https://faron.com/releases-and-publications/faron-pharmaceuticals-presents-promising-phase-1-2-data-from-bexmab-study-at-mds-2025-plenary-session/[9] Lantern Pharma Secures FDA Clearance for Planned Phase 1b/2 Trial of LP-184 in Biomarker-Defined, Treatment-Resistant NSCLC Patients with High Unmet Clinical Need. Retrieved May 16, 2025, from https://ir.lanternpharma.com/news-events/press-releases/detail/179/lantern-pharma-secures-fda-clearance-for-planned-phase-1b2[10] Innovo Therapeutics Announces Positive Phase 1 Results for INV-101, a Novel Immuno-Metabolic Modulator for Autoimmune Diseases. Retrieved May 16, 2025, from https://www.businesswire.com/news/home/20250512131551/en/Innovo-Therapeutics-Announces-Positive-Phase-1-Results-for-INV-101-a-Novel-Immuno-Metabolic-Modulator-for-Autoimmune-Diseases[11] Capsida Receives FDA IND Clearance for Its First-in-Class, IV-administered Gene Therapy for STXBP1 Developmental and Epileptic Encephalopathy. Retrieved May 16, 2025, from https://capsida.com/capsida-receives-fda-ind-clearance-for-its-first-in-class-iv-administered-gene-therapy-for-stxbp1-developmental-and-epileptic-encephalopathy/[12] AAVantgarde presents positive clinical data from its AAVB-081 program for Usher 1B and preclinical data from its AAVB-039 program for Stargardt at the ARVO 2025 annual meeting. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/12/3078987/0/en/AAVantgarde-presents-positive-clinical-data-from-its-AAVB-081-program-for-Usher-1B-and-preclinical-data-from-its-AAVB-039-program-for-Stargardt-at-the-ARVO-2025-annual-meeting.html[13] Artiva Biotherapeutics Announces Longer-term Phase 1/2 Data Demonstrating Prolonged Durability for AlloNK® in Combination with Rituximab in Patients with B-cell-Non-Hodgkin Lymphoma at the ASGCT 28th Annual Meeting. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/13/3080625/0/en/Artiva-Biotherapeutics-Announces-Longer-term-Phase-1-2-Data-Demonstrating-Prolonged-Durability-for-AlloNK-in-Combination-with-Rituximab-in-Patients-with-B-cell-Non-Hodgkin-Lymphoma.html[14] Sernova Biotherapeutics Provides Positive Interim Data from Ongoing Phase 1/2 Clinical Trial of Cell Pouch Bio-hybrid Organ in Patients Living with Type 1 Diabetes. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/14/3080975/0/en/Sernova-Biotherapeutics-Provides-Positive-Interim-Data-from-Ongoing-Phase-1-2-Clinical-Trial-of-Cell-Pouch-Bio-hybrid-Organ-in-Patients-Living-with-Type-1-Diabetes.html[15] Enliven Therapeutics Announces Updated Positive Data from Phase 1 Clinical Trial of ELVN-001 in CML and Oral Presentation at the EHA 2025 Congress. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-updated-positive-data-from-phase-1-clinical-trial-of-elvn-001-in-cml-and-oral-presentation-at-the-eha-2025-congress-302455412.html[16] AbCellera Receives Authorization from Health Canada to Initiate the Phase 1 Clinical Trial of ABCL635 for Vasomotor Symptoms Due to Menopause. Retrieved May 16, 2025, from https://investors.abcellera.com/news/news-releases/2025/AbCellera-Receives-Authorization-from-Health-Canada-to-Initiate-the-Phase-1-Clinical-Trial-of-ABCL635-for-Vasomotor-Symptoms-Due-to-Menopause/default.aspx[17] Biomea Fusion’s BMF-500 Selected for Poster Presentation at EHA 2025 Highlighting Phase I Data in Relapsed/Refractory Acute Leukemia. Retrieved May 16, 2025, from https://www.globenewswire.com/news-release/2025/05/14/3081603/0/en/Biomea-Fusion-s-BMF-500-Selected-for-Poster-Presentation-at-EHA-2025-Highlighting-Phase-I-Data-in-Relapsed-Refractory-Acute-Leukemia.html[18] Athira Pharma to Present Data from First-in-Human Phase 1 Clinical Trial of ATH-1105 at the 4th Annual ALS Drug Development Summit. Retrieved May 16, 2025, from https://investors.athira.com/news-releases/news-release-details/athira-pharma-present-data-first-human-phase-1-clinical-trial[19] Rocket Pharmaceuticals Presents Preliminary Data from Phase 1 Clinical Trial of RP-A601 for PKP2 Arrhythmogenic Cardiomyopathy at 28th Annual Meeting of the American Society of Gene and Cell Therapy. Retrieved May 16, 2025, from https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-presents-preliminary-data-phase-1[20] START Doses First U.S. Patient in Moderna's Phase 1 Clinical Trial of mRNA-4106, a Pan-Tumor Antigen Therapy Candidate, in Solid Tumors. Retrieved May 16, 2025, from https://www.prnewswire.com/news-releases/start-doses-first-us-patient-in-modernas-phase-1-clinical-trial-of-mrna-4106-a-pan-tumor-antigen-therapy-candidate-in-solid-tumors-302455728.html[21] Pasithea Therapeutics Announces Initiation of Phase 1/1B Study of PAS-004 in Adult NF1 Patients and Activation of First Clinical Trial Site. Retrieved May 16, 2025, from https://ir.pasithea.com/news-events/press-releases/detail/120/pasithea-therapeutics-announces-initiation-of-phase-11b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2