IDP-023

▎药明康德内容团队编辑 近期，全球细胞和基因疗法（CGT）领域迎来系列进展。Ultragenyx Pharmaceutical公司向美国FDA递交了其基因疗法UX111的上市申请，用于治疗IIIA型黏多糖贮积症（MPS IIIA）。用于治疗肺实体瘤的吸入式基因疗法KB707在晚期非小细胞肺癌（NSCLC）患者中表现良好，疾病控制率（DCR）达73%。用于治疗OTOF（耳铁蛋白）基因突变相关先天性耳聋的基因疗法SENS-501在前两名小患者中安全性良好，患儿行为已见到改善。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。 图片来源：123RF ———✦研发进展✦——— ◇ Ultragenyx Pharmaceutical公司宣布，已向美国FDA提交了生物制品许可申请（BLA），寻求加速批准其腺相关病毒（AAV）基因疗法UX111（ABO-102），用于治疗IIIA型黏多糖贮积症患者。今年早些时候，Ultragenyx与FDA达成协议，认为脑脊液（CSF）中的硫酸乙酰肝素（HS）是一个合理的替代终点，可用以支持UX111的加速批准。根据新闻稿，如果获得批准，UX111将成为获美国FDA批准用以治疗MPS IIIA的首款疗法。 ◇ Krystal Biotech公司公布了其吸入式基因疗法KB707用于治疗肺实体瘤的KYANITE-1研究的初步结果。KB707基于一种改良的HSV-1载体，旨在向肺部递送编码人类白细胞介素-12（IL-12）和IL-2的基因，并促进全身免疫介导的肿瘤清除。在该研究中，KB707显示出单药治疗活性的早期证据，在晚期NSCLC患者中最为显著。截至2024年12月6日的数据，11例疗效可评估NSCLC患者的客观缓解率（ORR）为27%，DCR为73%。 ◇ Sensorion公司公布了其基因疗法SENS-501用于治疗6至31个月大且未植入人工耳蜗的先天性耳聋婴孩患者的1/2期临床试验的初步数据，这些患者的耳聋与OTOF基因突变相关。SENS-501旨在通过AAV将OTOF基因的功能拷贝直接引入毛细胞中，从而恢复听力。此次公布的结果显示，前两名接受治疗的患者对SENS-501和外科手术的耐受性良好，并且研究人员在两名幼儿中都观察到令人鼓舞的行为改善。 ◇ Aurion Biotech公司公布了其现货型细胞疗法AURN001用于治疗继发于角膜内皮功能障碍的角膜水肿的1/2期临床试验的顶线数据。AURN001是一种由同种异体人角膜内皮细胞，和ROCK抑制剂Y-27632构成的细胞疗法组合产品，旨在作为一次性疗法注射到眼睛中。 该研究的主要终点是最佳矫正视力（BCVA）提高≥15个字母的患者比例。结果显示，高剂量AURN001组相较于单独使用Y-27632组，在这一指标上显示出统计学上的显著改善，为50%对比14.3%（p=0.020）。关键次要终点显示，与单独使用Y-27632组相比，高剂量AURN001组的BCVA和中央角膜厚度（CCT）的变化具有统计学意义改善。此外，在主要终点上观察到了剂量依赖性的改善趋势。安全性方面，所有剂量水平的AURN001通常耐受性良好，并且没有报告眼部严重不良事件。 ◇ Tenaya Therapeutics公司公布了其基因疗法TN-201用于治疗MYBPC3相关肥厚型心肌病（HCM）的1b/2期临床试验中首批患者的初步数据。结果显示，TN-201在3E13 vg/kg剂量下总体耐受性良好，能够在心脏中有效递送并表达目标基因，导致MYBPC3的mRNA和肌球蛋白结合蛋白C（MyBP-C）的水平随时间增加。心肌拉伤和损伤的循环生物标志物和其他临床指标大多保持稳定或有所改善。尽管如此，仍需更长时间的数据来全面评估TN-201的效果。 TN-201是一款基于AAV载体的潜在“first-in-class”基因疗法，旨在将人MYBPC3基因的全长拷贝递送给心肌细胞，恢复调节心肌收缩和舒张的肌球蛋白结合蛋白的正常水平，治疗MYBPC3相关HCM。 ◇ Kiromic BioPharma公司公布了其在研γ-δ T细胞（GDT）疗法Deltacel（KB-GDT-01）用于治疗IV期转移性NSCLC患者的1期临床试验的新数据。入组的首例患者目前病情稳定，无疾病进展或新发恶性肿瘤部位的证据，与治疗前相比，该患者的肿瘤大小减少了约27%，其无进展生存期（PFS）已达到11个月，没有报告不良事件。入组的第4名患者随访8个月的初步结果显示，与治疗前相比，肿瘤体积减少了约32%。该患者正持续获得临床益处，且无不良事件。入组的第7名患者已完成了治疗，并且对治疗的耐受性良好。 ◇ ViGeneron公司宣布，该公司为其在研基因疗法VG801递交的1/2临床试验的IND申请已经获得美国FDA许可，用于治疗Stargardt病和其他与ABCA4基因突变相关的视网膜营养不良。VG801采用ViGeneron专有的双AAV载体REVeRT（通过mRNA反式剪接重组）技术，解决了编码人类ABCA4的DNA序列（约6.7 kb）过大而无法装入单一AAV载体的难题。REVeRT由两个AAV载体构成，每个载体分别携带ABCA4编码序列的一半，产生两种独立的mRNA前体，这些mRNA前体通过反式剪接形成完整的mRNA，随后翻译成功能性蛋白。VG801还利用了一种新型vgAAV衣壳，基于ViGeneron专有vgAAV技术平台生成，旨在实现广泛的视网膜转导。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ Tessera Therapeutics公司宣布与比尔及梅琳达·盖茨基金会达成协议，共同资助Tessera的镰状细胞病（SCD）体内治疗项目。盖茨基金会的资助包括初期投资，并有可能追加投资至最高5000万美元，旨在支持Tessera的SCD项目进入临床阶段，并帮助其实现开发全球可及的变革性基因药物的目标。 Tessera正在开发用于SCD的基因书写疗法，旨在通过单次静脉注射在体内直接纠正导致SCD的基因突变，而无需进行复杂的干细胞动员或有毒的化疗预处理。此外，Tessera还利用其专有的非病毒递送平台开发了脂质纳米颗粒，以确保基因书写疗法能够精准递送到长期造血干细胞中。 ◇ Indapta Therapeutics公司宣布筹集了2250万美元以加速其差异化的同种异体自然杀伤（NK）细胞疗法的临床开发。该公司于近期公布了其同种异体NK细胞疗法IDP-023治疗晚期多发性骨髓瘤或非霍奇金淋巴瘤患者的1/2期临床试验结果。患者接受了1到3剂IDP-023，伴或不伴IL-2治疗。结果显示，在9名接受治疗的患者中，有5名患者观察到了客观缓解。此外，IDP-023联合CD20或CD38靶向单克隆抗体的队列招募正在进行中。 ◇ Inceptor Bio公司和沙砾生物（GRIT Bio）宣布建立战略合作伙伴关系，Inceptor Bio将授予沙砾生物其自体CD70靶向嵌合抗原受体（CAR）-T细胞疗法IB-T101在中国的独家许可，沙砾生物将负责监督开发、制造和商业化。Inceptor Bio有资格在IB-T101达到某些缓解标准后获得里程碑付款和特许权使用费，并计划利用此次合作的临床数据来支持其他地区的监管提交和开发。 IB-T101利用Inceptor Bio专有的OUTLAST平台对T细胞进行重编程，使其在恶劣的肿瘤微环境中具有卓越的干性、持久性和效应功能。该疗法旨在靶向透明细胞肾细胞癌中的CD70，是一种潜在的“best-in-class”疗法。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Ultragenyx Submits Biologics License Application to the U.S. FDA for UX111 AAV Gene Therapy for the Treatment of Sanfilippo Syndrome Type A (MPS IIIA). Retrieved December 19, 2024 from https://www.globenewswire.com/news-release/2024/12/19/2999800/20739/en/Ultragenyx-Submits-Biologics-License-Application-to-the-U-S-FDA-for-UX111-AAV-Gene-Therapy-for-the-Treatment-of-Sanfilippo-Syndrome-Type-A-MPS-IIIA.html [2] Kiromic BioPharma Reports 32% Decrease in Tumor Volume Eight Months Post-Treatment in Fourth Patient Enrolled in Deltacel-01. Retrieved December 19, 2024, from https://ir.kiromic.com/news-releases/news-release-details/kiromic-biopharma-reports-32-decrease-tumor-volume-eight-months [3] Tenaya Therapeutics Reports Promising Early Data from MyPEAK™-1 Phase 1b/2 Clinical Trial of TN-201 for Treatment of MYBPC3-Associated Hypertrophic Cardiomyopathy. Retrieved December 19, 2024, from https://www.globenewswire.com/news-release/2024/12/17/2998112/0/en/Tenaya-Therapeutics-Reports-Promising-Early-Data-from-MyPEAK-1-Phase-1b-2-Clinical-Trial-of-TN-201-for-Treatment-of-MYBPC3-Associated-Hypertrophic-Cardiomyopathy.html [4] ViGeneron Announces FDA Clearance of IND for Novel mRNA Trans-Splicing Gene Therapy VG801 to Treat Stargardt Disease and Other ABCA4-Linked Retinal Dystrophies. Retrieved December 18, 2024, from https://www.globenewswire.com/news-release/2024/12/18/2999005/0/en/ViGeneron-Announces-FDA-Clearance-of-IND-for-Novel-mRNA-Trans-Splicing-Gene-Therapy-VG801-to-Treat-Stargardt-Disease-and-Other-ABCA4-Linked-Retinal-Dystrophies.html [5] Sensorion Reports Data in the Audiogene Phase 1/2 Gene Therapy Clinical Trial. Retrieved December 19, 2024, from https://s27.q4cdn.com/232015521/files/doc_news/2024/12/2024-12-SENS_SENS501Results_ENG_FinalVersion.pdf [6] Krystal Biotech Announces Early Evidence of Monotherapy Activity in Heavily Pre-Treated Patients with Advanced Non-Small Cell Lung Cancer. Retrieved December 19, 2024, from https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-early-evidence-monotherapy-activity [7] Inceptor Bio and GRIT Bio Announce Strategic Partnership to Advance IB-T101, a Next-Generation Solid Tumor CAR-T Utilizing the OUTLAST™ Platform. Retrieved December 19, 2024, from https://www.prnewswire.com/news-releases/inceptor-bio-and-grit-bio-announce-strategic-partnership-to-advance-ib-t101-a-next-generation-solid-tumor-car-t-utilizing-the-outlast-platform-302334271.html [8] Indapta Therapeutics Raises $22.5M in Funding. Retrieved December 19, 2024, from https://www.finsmes.com/2024/12/indapta-therapeutics-raises-22-5m-in-funding.html [9] Tessera Therapeutics Receives Investment to Develop Curative In Vivo Genetic Treatment for Sickle Cell Disease. Retrieved December 19, 2024, from https://www.globenewswire.com/news-release/2024/12/18/2998899/0/en/Tessera-Therapeutics-Receives-Investment-to-Develop-Curative-In-Vivo-Genetic-Treatment-for-Sickle-Cell-Disease.html 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

HOUSTON & SEATTLE--( BUSINESS WIRE )--Indapta Therapeutics, Inc., a privately held clinical stage biotechnology company developing next-generation cell therapies for the treatment of cancer and autoimmune diseases, announced today it has closed a $22.5 million round of new financing to accelerate the clinical development of its differentiated allogeneic Natural Killer (NK) cell therapy. Current investors RA Capital Management, LP, Leaps by Bayer, the impact investment arm of Bayer AG, Vertex Ventures HC, Pontifax, and the Myeloma Investment Fund, the venture philanthropy subsidiary of the Multiple Myeloma Research Foundation, completed the round. "This funding will enable us to generate significant additional data in our ongoing trial of IDP-023 in cancer as well as initial data from our first trial in autoimmune disease," said Mark Frohlich, Indapta’s CEO. "Preliminary results of IDP-023 in cancer are encouraging and we look forward to initiating our Phase 1 trial for multiple sclerosis in Q1 2025. This financing, together with our recently announced collaboration with Sanofi, highlights the promise of our differentiated platform.” Advancing Clinical Trials of Lead Product IDP-023 Indapta has completed enrollment in the safety run-in portion of the Phase 1 clinical trial of IDP-023 in Non-Hodgkin’s Lymphoma (NHL) and Multiple Myeloma (MM), in which patients received up to three doses of IDP-023 without and with interleukin (IL)-2. As presented at the Society for Immunotherapy of Cancer meeting , the mean maximum decrease in serum M-protein or light chain was 73% in responding myeloma patients with relapsed/refractory disease, with three patients achieving a reduction of 84% or greater. Enrollment of cohorts receiving IDP-023 in combination with monoclonal antibodies targeting CD20 or CD38 is underway. In August, Indapta announced FDA clearance of its IND of IDP-023 in combination with ocrelizumab in progressive MS . The company’s approach is highly differentiated from other cellular approaches to autoimmune diseases, with at least three different mechanisms that can address the biology of the disease: 1) by combining with a B cell targeting antibody like ocrelizumab, IDP-023 can deplete B cells more effectively than antibody alone; 2) g-NK cells are capable of targeting autoreactive T and B cells that are known to upregulate HLA-E; and 3) given their inherent anti-viral activity, g-NK cells can potentially address the EBV viral reservoir that contributes to the disease pathogenesis. About Indapta Therapeutics Indapta is a privately-held company focused on developing and bringing to market a diverse pipeline of cell therapies to treat the still unmet medical needs of patients with blood and solid-tumor cancers as well as autoimmune diseases. The company’s proprietary robust platform of naturally-occurring g-NK cells is specifically designed to create best-in-class, highly potent, more accessible, and scalable cell therapies. For more information, please visit www.indapta.com .