▎药明康德内容团队编辑本期看点1. Solu Therapeutics公司创新细胞毒性靶向嵌合体(CyTAC)药物STX-0712的1期临床试验已完成首例患者给药。该类疗法能够靶向传统疗法难以作用的细胞表面蛋白。2. 用于治疗复发性生殖器疱疹的长效解旋酶-引物酶抑制剂ABI-5366的1a期临床试验数据积极,约20天的半衰期有望实现每周一次或每月一次的口服给药方案。药明康德内容团队整理STX-0712:1期临床试验完成首例患者给药Solu Therapeutics公司宣布完成4100万美元的A轮融资,所得资金将用于推进其核心项目STX-0712的临床评估、拓展其他管线,以及探索其细胞毒性靶向嵌合体和治疗指数控制靶向嵌合体(TicTAC)平台的新应用。该公司还宣布启动了STX-0712用于治疗耐药/难治性慢性粒单核细胞白血病(CMML)和其他血液系统恶性肿瘤的1期临床试验,首位患者已开始给药。Solu Therapeutics公司通过以独特的方式将强效、选择性小分子与效应抗体连接起来,能够靶向传统疗法难以作用的细胞表面蛋白(如G蛋白偶联受体和离子通道)。其双功能小分子的一只臂可特异性进入细胞表面蛋白中的深结合口袋,另一臂通过专有连接子技术与其专有的抗体连接,可增强效应抗体的疗效。STX-0712是一种CyTAC药物,通过靶向G蛋白偶联受体CCR2(在恶性单核细胞中高表达),能够清除CCR2阳性细胞,同时减少对正常细胞的影响,有望为耐药/难治性血液肿瘤提供更精准、有效的治疗选择。临床前数据显示,STX-0712对CMML患者样本中的CCR2阳性单核细胞具有强大的离体活性。ABI-5366:公布1a期临床试验的中期数据Assembly Biosciences公司公布了一种用于复发性生殖器疱疹的长效解旋酶-引物酶抑制剂ABI-5366的1a期临床试验数据。该候选疗法通过靶向病毒解旋酶-引物酶复合体发挥作用。这是一种在HSV-1和HSV-2中都保守的重要病毒酶复合体,并且宿主细胞中没有类似的酶复合体。在短期临床研究中,HSV解旋酶-引物酶抑制剂显示出比核苷类似物更佳的疗效潜力。此次公布的结果显示,ABI-5366在口服剂量高达350毫克时耐受性良好,未报告3级或4级治疗相关实验室异常或严重不良事件。此外,在所有剂量组中观察到ABI-5366的半衰期约为20天,有望实现每周一次或每月一次的口服给药方案。CVN293:公布1期临床试验数据Cerevance公司公布了其钾双孔结构域通道亚家族K成员13(KCNK13)抑制剂CVN293的积极1期临床试验结果。CVN293是一种高选择性口服KCNK13抑制剂,旨在通过抑制神经炎症减缓神经退行性疾病进展。KCNK13是一种潜在的NLRP3炎性小体激活的新型调节因子,该靶点由Cerevance公司专有的NETSseq平台发现。此次公布的研究结果显示,接受CVN293单次和14天内多次给药的健康成人对该药物的耐受性良好,100%的受试者完成了试验,未出现剂量限制性毒性、治疗相关停药或具临床意义的生命体征异常,所有不良事件均为轻度。CVN293还显示出强大的脑渗透性,支持KCNK13抑制剂对以神经炎症为特征的神经退行性疾病的效用。PALI-2108:1a期临床试验完成受试者给药Palisade Bio公司宣布,其用于治疗溃疡性结肠炎(UC)的在研药物PALI-2108已完成1a期临床试验,预计将于2025年5月底公布顶线数据。在UC和纤维狭窄型克罗恩病(FSCD)中,较高的PDE4B表达与局部炎症活动有关。PALI-2108是一种PDE4抑制剂前药,能在UC和FSCD等疾病部位局部活化,显著提升病变组织内PDE4抑制剂浓度,同时减少全身暴露,从而降低腹泻等传统PDE4抑制剂的副作用。初步结果显示,迄今为止未观察到与实验室检查或心电图相关的严重不良事件或治疗伴发不良事件。在临床前研究中,与其他PDE4抑制剂相比,PALI-2108对PDE4 B和D有很强的抑制作用。这些结果表明,在剂量相当的情况下,PALI-2108具有极佳的耐受性。ALX2004:IND申请获得FDA许可ALX Oncology公司宣布,其针对EGFR表达实体瘤的潜在“best-in-class”及“first-in-class”抗体偶联药物(ADC)ALX2004的IND申请已获FDA批准,计划于2025年中期启动单剂量递增及扩展的1期临床试验。ALX2004是通过该公司专有的拓扑异构酶I抑制剂有效载荷平台设计的,由三部分组成,分别是经优化的抗EGFR抗体骨架、稳定性增强的连接子,以及能产生强旁观者效应的专有拓扑异构酶I载荷,旨在克服早期EGFR靶向ADC因药物设计、脱靶毒性及传统载荷局限性导致的临床瓶颈。CVHNLC:IND申请获得FDA许可CureVac公司宣布,美国FDA已批准其基于mRNA的精准免疫疗法CVHNLC的IND申请,可启动针对鳞状非小细胞肺癌(sqNSCLC)患者的1期研究。CVHNLC由两种编码8种在sqNSCLC中常见的肿瘤相关抗原(TAA)的mRNA构建体组成,其中4种为已知的实体瘤相关抗原,另4种为CureVac专有发现平台鉴定的新TAA。该疗法采用第二代mRNA骨架,使用未修饰的mRNA封装于脂质纳米颗粒(LNP)中。该公司计划将CVHNLC与免疫检查点抑制剂pembrolizumab联用进行临床试验,旨在放大靶向抗肿瘤免疫反应。参考资料(可上下滑动查看)[1] IDEAYA Biosciences Announces Phase 1/2 Expansion for IDE397 and Trodelvy® Combination in MTAP-Deletion Urothelial Cancer. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-phase-12-expansion-for-ide397-and-trodelvy-combination-in-mtap-deletion-urothelial-cancer-302425193.html[2] ALX Oncology Receives IND Clearance from U.S. FDA for ALX2004, a Novel EGFR-targeted Antibody-drug Conjugate. Retrieved April 12, 2025, from https://ir.alxoncology.com/news-releases/news-release-details/alx-oncology-receives-ind-clearance-us-fda-alx2004-novel-egfr[3] CureVac Receives U.S. FDA IND Clearance to Initiate Phase 1 Clinical Trial for Novel mRNA-Based Precision Immunotherapy in Squamous Non-Small Cell Lung Cancer. Retrieved April 12, 2025, from https://www.curevac.com/en/curevac-receives-u-s-fda-ind-clearance-to-initiate-phase-1-clinical-trial-for-novel-mrna-based-precision-immunotherapy-in-squamous-non-small-cell-lung-cancer/[4] NKGen Biotech Presents Data from Phase 1/2a Clinical Trial of Troculeucel in Moderate Alzheimer’s Disease at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2025). Retrieved April 12, 2025, from https://nkgenbiotech.com/nkgen-biotech-presents-data-from-phase-1-2a-clinical-trial-of-troculeucel-in-moderate-alzheimers-disease-at-the-international-conference-on-alzheimers-and-parkinsons-disease/[5] Lexeo Therapeutics Announces Positive Interim Phase 1/2 Data for LX2006 in Friedreich Ataxia Cardiomyopathy Supporting Advancement to Registrational Study. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/07/3056510/0/en/Lexeo-Therapeutics-Announces-Positive-Interim-Phase-1-2-Data-for-LX2006-in-Friedreich-Ataxia-Cardiomyopathy-Supporting-Advancement-to-Registrational-Study.html[6] Palisade Bio Completes Dosing in Phase 1a Portion of Ongoing Phase 1a/b Study of PALI-2108. Retrieved April 12, 2025, from https://palisadebio.com/palisade-bio-completes-dosing-in-phase-1a-portion-of-ongoing-phase-1a-b-study-of-pali-2108/[7] SciTech Development Announces 2nd FDA Approval of a Phase 1 a/b IND For ST-001. New IND Targets the Treatment of Relapsed/Refractory Small Cell Lung Cancer Following Its Previous Approval in the Treatment of T-Cell NHL. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/scitech-development-announces-2nd-fda-approval-of-a-phase-1-ab-ind-for-st-001-new-ind-targets-the-treatment-of-relapsedrefractory-small-cell-lung-cancer-following-its-previous-approval-in-the-treatment-of-t-cell-nhl-302421487.html[8] Cerevance Presents Positive Results from Phase 1 Study of CVN293 at American Academy of Neurology 2025 Annual Meeting. Retrieved April 12, 2025, from https://www.cerevance.com/media/cerevance-presents-positive-results-from-phase-1-study-of-cvn293-at-american-academy-of-neurology-2025-annual-meeting[9] LifeMine Announces First Participant Dosed in First-in-human Phase 1 Clinical Trial of LIFE-001, Designed De Novo to Become a Field Dominating Immunosuppressive for Immune-mediated Disorders and Transplantation. Retrieved April 12, 2025, from https://www.businesswire.com/news/home/20250407523884/en/LifeMine-Announces-First-Participant-Dosed-in-First-in-human-Phase-1-Clinical-Trial-of-LIFE-001-Designed-De-Novo-to-Become-a-Field-Dominating-Immunosuppressive-for-Immune-mediated-Disorders-and-Transplantation[10] Neurona Therapeutics Presents Positive Clinical Data Update from NRTX-1001 Cell Therapy Trial in Drug-resistant Epilepsy at American Academy of Neurology Annual Meeting. Retrieved April 12, 2025, from https://www.neuronatherapeutics.com/news/press-releases/040825/[11] Opus Genetics Announces One-Month Clinical Data from Pediatric Patient in Phase 1/2 Trial of OPGx-LCA5 Gene Therapy in Inherited Retinal Diseases. Retrieved April 12, 2025, from https://ir.opusgtx.com/press-releases/detail/483/opus-genetics-announces-one-month-clinical-data-from-pediatric-patient-in-phase-12-trial-of-opgx-lca5-gene-therapy-in-inherited-retinal-diseases[12] Cytora Reports Successful Results of Phase 1/2a Trial of Stem Cell Treatment for Diabetic Foot Ulcers. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/cytora-reports-successful-results-of-phase-12a-trial-of-stem-cell-treatment-for-diabetic-foot-ulcers-302424359.html[13] KSQ Therapeutics Announces First Patient Dosed in Phase 1/2 Study for KSQ-004EX, a CRISPR/Cas9-Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058270/0/en/KSQ-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-2-Study-for-KSQ-004EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html[14] KSQ Therapeutics Announces First Patient Dosed in Phase 1/2 Study for KSQ-004EX, a CRISPR/Cas9-Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058270/0/en/KSQ-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-2-Study-for-KSQ-004EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html[15] Solu Therapeutics Closes $41M Series A Financing and Announces First Patient Dosed in Phase 1 Clinical Trial of STX-0712 in Patients with CMML and Other Advanced Hematologic Malignancies. Retrieved April 12, 2025, from https://cdn.prod.website-files.com/669551ccc7908830b842dc2b/67f55ddc890a926ab1f047c9_Final%20Solu%20press%20release_4.9.pdf[16] Context Therapeutics Doses First Patient in Phase 1 Clinical Trial of CT-95. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058314/0/en/index.html[17] Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 1, Multiple Ascending Dose LUMINA Trial of AMX0114 in People Living with Amyotrophic Lateral Sclerosis. Retrieved April 12, 2025, from https://www.amylyx.com/news/amylyx-pharmaceuticals-announces-first-participant-dosed-in-phase-1-multiple-ascending-dose-lumina-trial-of-amx0114-in-people-living-with-amyotrophic-lateral-sclerosis[18] Assembly Biosciences Presents New Data Highlighting Long-Acting Herpes Simplex Virus Candidate ABI-5366 and Genital Herpes Prevalence and Treatment Patterns at the 2025 ESCMID Congress. Retrieved April 12, 2025, from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-presents-new-data-highlighting-long-acting[19] Seismic Therapeutic Doses First Cohort in Phase 1 Clinical Trial of S-4321, a Novel Bifunctional Antibody that Agonizes PD-1 and FcγRIIb Inhibitory Receptors for the Treatment of Autoimmune Disease. Retrieved April 12, 2025, from https://seismictx.com/seismic-therapeutic-doses-first-cohort-in-phase-1-clinical-trial-of-s-4321-a-novel-bifunctional-antibody-that-agonizes-pd-1-and-fc%ce%b3riib-inhibitory-receptors-for-the-treatment-of-autoimmune-disea/免责声明:药明康德内容团队专注介绍全球生物医药健康研究进展。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:本文来自药明康德内容团队,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