CD20-targeted CAR T cell therapy (Mustang Bio)

免费早鸟票，200张限量领取2026年1月23日医麦客新闻eMedClubNews近期，ImmunityBio公布了一项关于QUILT-106的临床试验的最新疗效与安全性数据，该试验旨在评估一款同种异体CD19CAR-NK疗法联合利妥昔单抗治疗华氏巨球蛋白血症的疗效和安全性。该公司的CD19CAR-NK搭载了高亲和力CD16受体（即FcγRIIIa158V），具有双重抗肿瘤机制：一方面通过CAR介导的细胞毒性作用直接杀伤肿瘤细胞；另一方面与抗CD20抗体利妥昔单抗联用时，可增强抗体依赖性细胞介导的细胞毒性作用。因此，当二者联用时，可实现对CD19/CD20淋巴瘤细胞的靶向杀伤，进而提升肿瘤细胞清除效率。数据显示，已经有4名患者入组，实现100%疾病控制率（DCR）。其中，2名患者目前正在接受长期随访评估，分别在治疗结束后7个月和15个月时仍保持完全缓解（CR），无需进一步治疗。这两名患者在基线时病情均较为严重，其中一名患者的骨髓受累范围约为95%，另一名患者存在多发性淋巴瘤骨病灶，但仅经过四剂治疗后即达到缓解。▲图片来源：官网值得一提的是，据ImmunityBio新闻稿称，这是首款无需化疗、无需淋巴细胞清除预处理的CAR-NK细胞疗法，并且ImmunityBio还手握一款已经获批上市的IL-15超级激动剂Anktiva，其能够有效刺激和扩增NK细胞，能够与CD19CAR-NK管线形成协同优势。ImmunityBio创始人、执行主席兼全球首席医疗与科学官PatrickSoon-Shiong表示：“这次更新的后续进一步验证了恢复和激活免疫系统可以在不使用化疗或淋巴细胞耗尽的情况下实现持久的疾病控制。在已用尽可用治疗方案的患者中，治疗停止后一年内仍能持续完全缓解，这对罕见的华氏巨球蛋白血症患者来说是一项有意义的进展，也验证了CAR-NK作为潜在下一代免疫治疗平台的潜力。”门诊细胞疗法ImmunityBio的QUILT-106试验成果，不仅为复发难治性华氏巨球蛋白血症患者带来了潜在治疗手段，更以「无需化疗、无需淋巴细胞清除预处理」的突破性特征，颠覆了传统细胞疗法的治疗范式，推动细胞疗法向「门诊可及」的模式转变。而目前，这也是细胞疗法发展的一大趋势，已经有多家企业进行了探索。CAR-NK/NKArtivaBiotherapeutics开发了一款脐带血来源、同种异体、冷冻保存、非转基因、ADCC增强的NK细胞治疗候选药物AB-101（AlloNK），可在门诊与单克隆抗体或先天细胞接合剂联合使用，针对自身免疫性疾病。该候选管线早在2023年即获得FDA批准开展临床，是同种异体NK细胞疗法首次用于治疗自身免疫性疾病。目前，其正在进行II期篮式试验，涵盖类风湿关节炎、干燥综合征、特发性炎症性肌病和系统性硬化症患者。在2025年的ASGCT第28届年会上，Artiva公布了AB-101联合利妥昔单抗在复发/难治性B细胞非霍奇金淋巴瘤的1/2期临床研究数据：在既往未接受CAR-T治疗的14名患者中，CR达到64%，截止2025年3月7日数据截点，缓解持续时间至少为19.4个月，大多数接受治疗的患者维持完全缓解状态。Artiva公司首席执行官曾表示，这是目前所有异体细胞治疗中针对重度预处理侵袭性B细胞NHL患者最具活性和持久性的数据之一，与已批准的部分自体CAR-T细胞治疗效果相当。据悉，今年上半年，Artiva计划将公布15例以上难治性类风湿关节炎患者的初步临床反应数据。CAR-T相较于门诊CAR-NK/NK，CAR-T基于技术积累和迭代，成为门诊细胞疗法竞争的核心阵地之一。门诊CAR-NK/NK的探索多聚焦于异体通用型技术路径，以安全性突破为核心抓手，门诊CAR-T的研发则呈现技术路线多元化特征——既有通过基因编辑优化CAR-T、降低免疫原性与毒副作用以适配门诊场景的方向，也有以体内CAR-T为代表的颠覆性技术，实现类似常规药物的门诊静脉输注给药。上市的CAR-T细胞疗法已经在进行门诊可行性的探索，如Yescarta、Tecartus、Kymriah等。2025年，一篇题为「Feasibilityofaxicabtageneciloleucelintheoutpatientsetting:primaryanalysisofprospectivetrial」的文章报道了一项单中心非随机开放标签前瞻性临床试验（NCT05108805），评估了利用可穿戴设备和远程医疗，评估门诊使用Yescarta治疗复发/难治性弥漫性B细胞淋巴瘤（R/RDLBCL）的可行性和安全性。2021年11月至2023年10月期间，本研究共入组25例患者，实际接受治疗的患者为20例，中位随访时间为374天。研究中，患者的淋巴细胞清除化疗及CAR-T输注均在门诊完成。19例因CRS住院（中位住院5.5天，历史住院数据为15天），1年无进展生存率（PFS）和总生存率（OS）分别为68%和74%。研究表明，门诊Yescarta管理可行且安全性可控，显著减少住院负担。在研疗法中，ImmixBiopharma的NXC-201是一款靶向BCMA的CAR-T疗法，拟用于治疗AL淀粉样变性。其CAR结构经过优化设计，使得NXC-201具有高转导率、高持久性、低脱靶率的特点，能够以更低的剂量达到更好的效果，降低由剂量导致的毒性，同时这一候选产品的持久性也得到提升，能够长时间在体内发挥作用，减少细胞耗竭的发生，这些特点也支持患者在门诊中使用。2025年12月，ImmixBiopharma公布了NXC-201治疗复发/难治性轻链型淀粉样变性的II期临床试验试验结果：20例患者中有15例达到完全缓解（CR为75%），5例疗效待评估患者中，4例骨髓微小残留病检测阴性，这一指标预示其后续有望达到完全缓解，或将使该疗法远期完全缓解率提升至95%。据悉，该公司计划在今年提交BLA。另外，MustangBio的MB-106是一种全人、第三代、CD20靶向CAR-T细胞疗法，含有4-1BB和CD28共刺激结构域、改良的IgG1间隔区消除了FcR结合，可支持通过门诊给药。此前，MustangBio公布的数据显示，MB-106治疗的华氏巨球蛋白血症（WM）患者的ORR高达90%，其中一位患者持久完全缓解达31个月。总结过去，传统细胞疗法因需住院严密监测并管理CRS、ICANS等严重副作用，既加重了患者经济负担，又导致患者生活质量下降。而门诊细胞疗法的发展，无论是无需化疗预处理的CAR-NK、经结构优化降低毒性的CAR-T，还是依托远程监测技术实现风险管控的已上市CAR-T门诊探索，都在从技术革新与模式创新双向突破这一困境。未来，细胞疗法将呈现「技术多元化、场景泛化、疗效与安全性双提升」的趋势，同时，有望重构细胞治疗临床服务模式。责任编辑丨浔校对丨浔参考资料：1.企业官网及公开资料精彩活动推荐11月29日19:00-20:30TFF膜包清洁重复验证与新版PDATR26技术报告解读声明：本文旨在于传递行业发展信息、探究生物医药前沿进展。文章内容仅代表作者观点，并不代表医麦客立场，亦不构成任何价值判断、投资建议或医疗指导，如有需求请咨询专业人士投资或前往正规医院就诊。版权说明：欢迎个人转发文章至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。如需转载请在文章下方留言获取授权。封面来源网络，如有侵犯版权，请联系删除点点“分享”、“点赞”和“在看”给我充点儿电吧~

Median Overall Survival (OS) of 15 months for subjects with complete remission (n=8) Median OS of 2nd Line efficacy evaluable population of 12 months (n=9) Median OS of Intent to Treat population (1L-7L) of 9 months (n=22) OS demonstrated by Annamycin in the MB-106 trial is significantly above industry expectations for relapsed AML (4-6 months) Clinical study report anticipated in Q1 2026 Company continues to execute Part A of the pivotal MIRACLE Phase 3 trial HOUSTON, Aug. 27, 2025 (GLOBE NEWSWIRE) — Moleculin Biotech, Inc., (Nasdaq: MBRX) (“Moleculin” or the “Company”), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, today announced the completion of its Phase 1B/2 (MB-106) clinical trial evaluating Annamycin in combination with Cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with acute myeloid leukemia (AML). Database lock for the trial is expected by the end of September, with the final clinical study report (CSR) projected to be published in early Q1 2026. In total, 22 subjects were enrolled in the trial, with all subjects (1L-7L) who received AnnAraC per protocol having completed their efficacy evaluations (n=20). The updated overall survival (OS) data reveal the following: Median OS for Complete Remissions (CR): 15 months (n=8) with 4 subjects alive at study close Median OS for the intent to treat (ITT) Population (1L-7L): 9 months (n=22; 13 subjects experienced an event, 9 subjects censored) Median OS for 2L Efficacy Evaluable Population: 12 months (n=9) “Industry publications1 note that the typical OS for relapsed AML patients is roughly 4-6 months, these results highlight a remarkable improvement, exceeding expectations by 30% or more,” said Walter Klemp, Chairman and CEO of Moleculin Biotech. As previously reported, 8 subjects in the ITT population of 22 (36%) achieved a complete remission (CR) following treatment with AnnAraC. Among the subjects treated in the second line (2L) setting (n=10), the CR rate (the same primary efficacy endpoint as in the ongoing Phase 2B/3 pivotal MIRACLE trial), was 50%. Median durability for the 8 subjects achieving a CR was 10 months and continuing at the end of the study. CR durability ranged from 2 months to 22 months. CRs were achieved in subjects with a variety of prior treatments, including traditional 7+3 and venetoclax regimens. “We are glad to finally be in a position to close out our last Phase 2 AML trial, MB-106 by having completed follow-up on all subjects – some with durable CRs continuing – with database lock expected by the end of next month. While still technically preliminary, we are extremely pleased with the results of the MB-106 trial and look forward to the final CSR. These 2L data formed the basis for the design of the Phase 2B/3 pivotal MIRACLE trial with which we aim to gain eventual approval of Annamycin to serve the unmet need in 2L AML,” added Walter Klemp, Chairman and CEO of Moleculin. “We continue to see meaningful, positive trends across all data points, particularly in overall survival and durability. Of note, an 80+ yr old subject who achieved a CR with one cycle of Annamycin and then received two maintenance cycles of Annamycin finally relapsed after 600+ days. He then received a fourth round of Annamycin under compassionate use and is now back in remission. These data are very exciting and continue to give us hope that Annamycin has the potential to address the significant unmet need for safe and effective therapies for R/R AML. We also need to reemphasize that we have not seen any cardiotoxicity in any of the subjects to date, a key aspect of Annamycin.” “We can now also report that 50% of subjects achieving CR moved on to a curative bone marrow transplant, which is the most sought-after goal of any induction therapy in AML,” Mr. Klemp continued. “The results we have seen in 2L patients are better than any drug ever approved for second line AML and more than double the average for the last five drugs approved for 2L use.” “Looking ahead, we are focused on driving Part A of our Phase 3 MIRACLE trial forward and remain on track recruit the first 45 enrolled patients before the end of this year on which safety and efficacy will be unblinded. The final data from MB-106, coupled with the expected data from the MIRACLE trial will be invaluable as we continue to unlock the full potential of Annamycin for the treatment of AML,” concluded Mr. Klemp. The median age of subjects in MB-106 is 68 years. A total of 18 subjects had relapsed/refractory AML and 4 subjects were first line treatment. Two subjects discontinued early due to allergic reactions. All subjects who completed treatment had undergone post therapy disease response assessments (bone marrow assessment and/or peripheral blood evaluation) (Day 15 or later). No clinically significant signs of cardiotoxicity were noted during or after treatment in any of the subjects enrolled. The combination was well tolerated with myelosuppression and infections being the main adverse events (AEs). All data from MB-106 is preliminary and subject to change. Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA. The Company is currently evaluating Annamycin in combination with Cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as “AnnAraC”) in a Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML). This global Phase 3 “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) includes sites in the US, Europe and the Middle East. For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00. 1 – Bruno C. Medeiros, Is there a standard of care for relapsed AML?, Best Practice & Research Clinical, Haematology, Volume 31, Issue 4, 2018, Pages 384-386, ISSN 1521-6926; Roboz GJ, Sanz G, et al. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062. PMID: 38231126; PMCID: PMC11103175.; Faderl S, Wetzler M, et al. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14. PMID: 22585697; PMCID: PMC4874149. About Moleculin Biotech, Inc. Moleculin Biotech, Inc. is a Phase 3 clinical stage pharmaceutical company advancing a pipeline of therapeutic candidates addressing hard-to-treat tumors and viruses. The Company’s lead program, Annamycin, is a next-generation highly efficacious and well tolerated anthracycline designed to avoid multidrug resistance mechanisms and to lack the cardiotoxicity common with currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. The Company has begun the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design Phase 3 trial evaluating Annamycin in combination with cytarabine, together referred to as AnnAraC, for the treatment of relapsed or refractory acute myeloid leukemia. Following a successful Phase 1B/2 study (MB-106), with input from the FDA, the Company believes it has substantially de-risked the development pathway towards a potential approval for Annamycin for the treatment of AML. This study remains subject to appropriate future filings with potential additional feedback from the FDA and their foreign equivalents. Additionally, the Company is developing WP1066, an Immune/Transcription Modulator capable of inhibiting p-STAT3 and other oncogenic transcription factors while also stimulating a natural immune response, targeting brain tumors, pancreatic and other cancers. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of pathogenic viruses, as well as certain cancer indications. For more information about the Company, please visit www.moleculin.com and connect on X, LinkedIn and Facebook. Forward-Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. Forward-looking statements in this press release include, without limitation, the timing of the MB-106 database lock for the trial and the publication of the final CSR, the timing of the release of the initial data on the first 45 subjects in the MIRACLE trial, and the Company’s ability to reconcile the US and EU MIRACLE protocols with the FDA and EMA, respectively. Moleculin will require significant additional financing, for which the Company has no commitments, in order to conduct its clinical trials as described in this press release, and the milestones described in this press release assume the Company’s ability to secure such financing on a timely basis. Although Moleculin believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Moleculin has attempted to identify forward-looking statements by terminology including ‘believes,’ ‘estimates,’ ‘anticipates,’ ‘expects,’ ‘plans,’ ‘projects,’ ‘intends,’ ‘potential,’ ‘may,’ ‘could,’ ‘might,’ ‘will,’ ‘should,’ ‘approximately’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including those discussed under Item 1A. “Risk Factors” in our most recently filed Form 10-K filed with the Securities and Exchange Commission (SEC) and updated from time to time in our Form 10-Q filings and in our other public filings with the SEC. Any forward-looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. Investor Contact:JTC Team, LLCJenene Thomas(908) 824-0775MBRX@jtcir.com