AIC-100

NATICK, Mass.--( BUSINESS WIRE )-- AffyImmune , a clinical-stage biotechnology company committed to developing novel, first-in-class chimeric antigen receptor (CAR) T cell therapies, announced today the designation of Regenerative Medicine Advanced Therapy (RMAT) by the U.S. Food and Drug Administration (FDA) for its CAR T-cell product candidate, AIC100 as a potential treatment for patients with recurrent anaplastic thyroid cancer (ATC), the most aggressive form of the disease. “We believe this important recognition from the FDA further supports the therapeutic potential of AIC100 to change the current treatment paradigm in advanced thyroid cancer and potentially other forms of aggressive solid tumors,” said Daniel Janse, Ph.D., CEO at AffyImmune. “RMAT designation was granted following the FDA’s review of safety and efficacy data from the first ten patients dosed with AIC100 in our Phase 1 study. We believe the RMAT designation reinforces the potential ability of AIC100 to meet the high unmet medical need in recurrent ATC, an aggressive disease where a standard of care is currently not available.” RMAT designation was designed to expedite the development and review of regenerative medicine therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious condition, and preliminary clinical evidence indicates the therapy has the potential to address unmet medical needs for the disease. Sponsor companies receiving RMAT designation can benefit from increased interactions with the FDA involving senior managers, with the goal of expediting drug development. “We remain focused on advancing the development of AIC100 for patients and families living with this devastating cancer,” said Sonal Gupta, M.D., Ph.D., Senior Vice President and Head of Clinical Development. “Receiving RMAT designation helps facilitate this goal by enabling increased dialogue with the FDA to expedite our development plan for our affinity-tuned CAR T therapy. We look forward to working closely with the FDA and other regulatory agencies as we continue to advance this program.” At ASCO 2024, AffyImmune reported interim results from their Phase 1 study evaluating the safety and efficacy of AIC100, an ICAM-1 targeting and affinity-tuned LFA-1 binder CAR T-cell therapy, in patients with advanced thyroid cancer. Notably, a metabolic complete response was achieved in one patient with ATC, the most aggressive form of the disease. For more information about the Phase 1 study, visit www.clinicaltrials.gov (NCT04420754). About AffyImmune Therapeutics AffyImmune is a clinical-stage biopharmaceutical company committed to developing a first-in-class, ICAM-1 targeting and affinity-tuned LFA-1 binder CAR T therapy to transform the lives of patients with advanced solid cancers. The Company’s proprietary technology utilizing ICAM-1/LFA-1 interaction can potentially address the critical CAR T challenges such as toxicity, antigen loss, T-cell trafficking and exhaustion, while also allowing in vivo tracking of the CAR T cells. Its lead candidate, AIC100, is currently in a Phase 1 study to treat patients with advanced thyroid cancers including advanced differentiated thyroid cancer and ATC. AffyImmune is developing a focused pipeline in ICAM-1-positive cancers with high unmet medical need. AffyImmune is based in Natick, Massachusetts. For more information, visit www.affyimmune.com .

▎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。Atara Biotherapeutics公司的突破性现货型T细胞疗法tabelecleucel（tab-cel）已向FDA递交了上市申请。在Orca Bio公司的在研同种异体T细胞免疫疗法Orca-T治疗急性髓系白血病（AML）的1期研究中，患者的一年总生存率达100%。一款HER2靶向的嵌合抗原受体（CAR）T细胞疗法在临床试验中使1名肉瘤患者保持完全缓解已超过6年。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✦———◇ Atara Biotherapeutics宣布已向美国FDA提交了tabelecleucel（tab-cel）的生物制品许可申请（BLA），以申请tab-cel作为单药疗法，用于治疗爱泼斯坦-巴尔病毒（EBV）阳性的移植后淋巴增殖性疾病（PTLD）。患者群体包括至少接受过一次治疗的成人以及两岁以上儿科患者。新闻稿指出，如果获批，tab-cel将成为FDA批准的首款同种异体T细胞疗法，以及治疗EBV阳性PTLD的首款疗法。Tab-cel是一种同种异体的EBV特异性T细胞免疫疗法，旨在靶向并消除EBV感染的细胞。在关键性临床试验ALLELE中，tab-cel的客观缓解率（ORR）达48.8%。此前，tab-cel（商品名：Ebvallo）已被欧盟委员会以及英国和瑞士的监管机构批准上市。在这三个地区，Ebvallo被批准作为单药疗法，治疗至少接受过一次治疗的复发/难治性EBV阳性PTLD成人患者，以及两岁以上儿科患者。去年11月，Pierre Fabre Laboratories和Atara Biotherapeutics达成合作协议，Pierre Fabre Laboratories囊获tab-cel的全球开发和商业化权益。◇ NKGen Biotech公司宣布，安全审查委员会已批准其在研NK细胞疗法SNK01进入阿尔茨海默病（AD）的2期临床试验，预计在2024年第二季度启动。SNK01是一款自体、非基因工程改造的NK细胞产品。它具有增强的细胞毒性和激活性受体的表达。此前公布的1期试验结果显示，SNK01除了先前披露的对淀粉样蛋白β（Aβ）和神经炎症生物标志物的积极影响外，对晚期AD患者的认知功能也具有临床疗效。在10名可评估的AD患者中，90%患者的阿尔茨海默病综合评分（ADCOMS）较基线时有改善或保持稳定。◇ Orca Bio公司公布了其在研同种异体T细胞免疫疗法Orca-T用于治疗AML患者的1b期临床试验的积极结果。接受Orca-T治疗的37例AML患者中，12个月的无复发生存率和总生存率分别为82.5%和100%，12个月的非复发死亡率为0%。Orca-T在该患者亚组中的安全性与更大范围的1b期人群一致，没有发现新的安全性信号。Orca-T目前正在美国各大治疗中心进行关键性的3期临床试验评估。Orca-T由富集的CD34+干细胞，以及通过高精度平台纯化、取材自单倍体匹配供体的特定T细胞亚群组合而成。Orca-Q有潜力改善患者的预后和降低移植物抗宿主疾病（GvHD）风险，并且无需对无法找到人类白细胞抗原（HLA）匹配的患者进行移植后环磷酰胺（PTCy）治疗。◇ iCell Gene Therapeutics公布了其BCMA与CD19靶向复合嵌合抗原受体-T（BCMA-CD19 cCAR-T）细胞免疫疗法的研究者发起临床试验（IIT）的积极结果。分析显示，所有接受足量初始剂量cCAR-T治疗的系统性红斑狼疮（SLE）/狼疮性肾炎（LN）患者，在治疗3个月后体内自身抗体呈现阴性，并在随访46个月时，均达到无症状和无药物缓解（MFR）。▲iCell的BCMA-CD19 cCAR-T疗法作用机制（图片来源：参考资料[12]）这款由iCell所设计的cCAR-T细胞免疫疗法，在单一结构中表达两种不同且功能齐全的CAR分子，一种靶向B细胞上的CD19，另一种靶向浆细胞上的BCMA。鉴于B细胞和长寿浆细胞具有独立的记忆，因此需要同时靶向B细胞和长寿浆细胞以消除所有升高的自身抗体。◇ AffyImmune Therapeutics公司公布了细胞间粘附分子-1（ICAM-1）靶向CAR-T细胞疗法AIC100治疗晚期甲状腺癌的1期临床试验数据。结果显示，在6例可评估的患者中，ORR为33%，其中一名患者获得了持久的部分缓解（PR），一名患有侵袭性甲状腺未分化癌的患者获得了持久的代谢完全缓解（mCR），该患者可以停止所有化疗。该研究中的疾病控制率（DCR）为67%。◇ Anixa Biosciences公司宣布其新型CAR-T细胞疗法治疗卵巢癌的1期临床试验已开始第5位患者的治疗。Anixa公司的CAR-T疗法是一种自体细胞疗法，由针对促卵泡激素受体（FSHR）的工程T细胞组成。FSHR在免疫学上只存在于卵巢的颗粒细胞中。由于靶点是一种嵌合内分泌（CE）受体，而靶点结合域来自其天然配体，因此这种技术被称为CER-T（嵌合内分泌受体T）细胞疗法，是一种新型CAR-T细胞疗法。◇ 美国得克萨斯儿童医院和贝勒医学院的研究团队近期在Nature Cancer杂志上领衔发表了一篇论文，内容是关于一种HER2特异性CAR-T细胞疗法治疗晚期肉瘤患者的1期临床试验结果。在接受治疗的14名患者中，有7名（50%）患者的病情得到稳定或缓解。中位随访时间为8.2个月时，患者的1年生存率为46%。一名患者在接受多次CAR-T细胞输注后达到完全缓解，并持续缓解超过6年。安全性方面，大多数患者出现了细胞因子释放综合征（CRS），但均可通过支持性治疗得到控制。没有观察到与HER2 CAR-T细胞相关的严重神经毒性或心脏毒性。▲患者的生存曲线和无进展生存曲线（图片来源：参考资料[4]）◇ NKGen Biotech公司公布了其非基因修饰的异体NK细胞SNK02治疗晚期实体瘤患者的1期临床试验的中期结果。结果显示，100%的患者（n=4）在完成8个周期的SNK02治疗后实现了疾病稳定（SD）的最佳客观缓解。此外，SNK02作为单一疗法的耐受性良好。SNK02有望成为潜在“first-in-class”的低温保存的异体NK细胞疗法，用于治疗实体瘤。这种疗法在给药前不需要进行淋巴清除，这可能会使其在未来与免疫检查点抑制剂联用时产生更好的整体协同作用。◇ Antion Biosciences公司宣布将开发新一代CD19靶向CAR-T细胞疗法，用于治疗B细胞驱动的自身免疫性疾病。Antion公司基于微RNA（miRNA）的miCAR技术平台能够将单个基因载体中多个基因的共同表达和沉默无缝地整合在一起。与其他基因工程技术相比，这种方法只需一个基因递送步骤就能安全高效地制造出多重工程细胞。▲miCAR技术平台图示（图片来源：Antion Biosciences公司官网）Antion公司的多重工程细胞旨在解决现有细胞疗法产品的关键限制。例如，其细胞产品经过基因工程改造提升了安全性，能够规避传统细胞疗法使用前的化疗预处理，并进一步减轻炎症风险。作为一种同种异体现货型细胞疗法，它能够规模化生产，满足全球患者的需求。———✦融资、合作、M&A✦———图片来源：123RF◇ Captain T Cell公司宣布完成了850万欧元的种子轮融资，该资金将用于进一步推动其潜在“first-in-class”主打产品进入临床，以及用于开发针对实体瘤的新型现货型同种异体细胞疗法平台。i&i Biotech Fund I、Brandenburg Kapital和HIL-INVENT等经验丰富的生命科学投资者参与了本轮融资。利用新一代技术，Captain T Cell公司生产的T细胞受体（TCR）T细胞具有更强的持久性，能够应对难治性实体瘤的恶劣肿瘤微环境。在临床前的体内模型中，这些功效增强的T细胞能够彻底根除侵袭性的肿瘤。◇ Indapta Therapeutics公司宣布获得了得克萨斯州癌症预防与研究所（CPRIT）授予的450万美元的资助，该资金将支持Indapta公司用于治疗晚期非霍奇金淋巴瘤和多发性骨髓瘤患者的主打NK细胞疗法IDP-023的临床开发。Indapta Therapeutics的NK细胞疗法基于NK细胞的特定亚群。这一名为g-NK的细胞亚群能够在不需要基因工程改造的情况下，显著增强单克隆抗体的肿瘤杀伤能力。G-NK细胞的产生源于NK细胞接触巨细胞病毒（CMV）后产生的表观遗传学变化。Indapta的技术平台可以从健康供体中倾向性扩增g-NK细胞，从而生产IDP-023。这一现货型细胞疗法的差异化特征在于它是一种可以冷冻保存的细胞疗法，并且与传统NK细胞相比，能够释放更多免疫激活细胞因子和肿瘤杀伤化合物。Indapta Therapeutics公司的首席执行官Mark Frohlich博士在接受药明康德内容团队采访时表示，在目前获批的疗法中，每一种细胞疗法只能针对一种癌症抗原。然而癌症抗原表达有着固有异质性，尤其是在面临选择性压力时，这促成了肿瘤的难治性或复发。该公司相信g-NK细胞有望成为一种“best-in-class”的NK细胞疗法，特别是当它与单克隆抗体或先天免疫双特异性衔接分子等靶向疗法联合使用，可以靶向多种癌症抗原并解决肿瘤异质性问题。相关阅读：单一疗法便能覆盖多种癌症抗原，“全能型”肿瘤NK细胞疗法是如何诞生的 | 迅猛新分子▲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] Atara Biotherapeutics Submits Tabelecleucel (Tab-cel®) Biologics License Application for Treatment of Epstein-Barr Virus Positive Post-Transplant Lymphoproliferative Disease with U.S. FDA. Retrieved May 20, 2024, from https://www.businesswire.com/news/home/20240520985176/en[2] NKGen Biotech’s SNK01 NK Cell Therapy Cleared to Start Phase 2 Clinical Trial in Alzheimer’s Disease. Retrieved May 23, 2024, from https://nkgenbiotech.com/nkgen-biotechs-snk01-nk-cell-therapy-cleared-to-start-phase-2-clinical-trial-in-alzheimers-disease/[3] Anixa Biosciences Commences Treatment of Fifth Patient in Ovarian Cancer CAR-T Clinical Trial. Retrieved May 23, 2024, from https://www.prnewswire.com/news-releases/anixa-biosciences-commences-treatment-of-fifth-patient-in-ovarian-cancer-car-t-clinical-trial-302150758.html[4] Hegde M, Navai S, DeRenzo C, Joseph SK, Sanber K, Wu M, Gad AZ, Janeway KA, Campbell M, Mullikin D, Nawas Z, Robertson C, Mathew PR, Zhang H, Mehta B, Bhat RR, Major A, Shree A, Gerken C, Kalra M, Chakraborty R, Thakkar SG, Dakhova O, Salsman VS, Grilley B, Lapteva N, Gee A, Dotti G, Bao R, Salem AH, Wang T, Brenner MK, Heslop HE, Wels WS, Hicks MJ, Gottschalk S, Ahmed N. Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial. Nat Cancer. 2024 Apr 24. doi: 10.1038/s43018-024-00749-6. Epub ahead of print. PMID: 38658775.[5] Antion Biosciences announces development of safety-enhanced and off-the-shelf CAR T-cells for autoimmune disease. Retrieved May 23, 2024, from https://www.globenewswire.com/news-release/2024/05/22/2886347/0/en/Antion-Biosciences-announces-development-of-safety-enhanced-and-off-the-shelf-CAR-T-cells-for-autoimmune-disease.html[6] Captain T Cell Secures Seed Financing Round Totaling € 8.5 Million. Retrieved May 23, 2024, from https://www.globenewswire.com/news-release/2024/05/22/2886221/0/en/Captain-T-Cell-Secures-Seed-Financing-Round-Totaling-8-5-Million.html[7] Indapta Therapeutics Awarded $4.5 Million by CPRIT to Advance Clinical Development of its Allogenic Natural Killer Cell Therapy. Retrieved May 23, 2024, from https://www.businesswire.com/news/home/20240521592452/en/[8] NKGen Biotech Publishes Phase 1 Interim Analysis Results of SNK02 Allogeneic NK Cell Therapy in Advanced Solid Tumors at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved May 24, 2024, from https://www.globenewswire.com/news-release/2024/05/23/2887701/0/en/NKGen-Biotech-Publishes-Phase-1-Interim-Analysis-Results-of-SNK02-Allogeneic-NK-Cell-Therapy-in-Advanced-Solid-Tumors-at-the-2024-American-Society-of-Clinical-Oncology-ASCO-Annual-.html[9] Orca Bio to Present Positive Clinical Outcomes with Orca-T in Patients with AML at 2024 ASCO Annual Meeting. Retrieved May 24, 2024, from https://www.businesswire.com/news/home/20240523266449/en/[10] AffyImmune Announces Confirmed Complete Response in Patient with Anaplastic Thyroid Cancer. Retrieved May 24, 2024, from https://www.businesswire.com/news/home/20240523653892/en[11] iCell Gene Therapeutics Announces Positive Clinical Data from Investigator Initiated Phase 1 Trial Evaluating BCMA-CD19 Compound CAR in Patients with Systemic Lupus Erythematosus/Lupus Nephritis Published in Annals of the Rheumatic Diseases. Retrieved May 24, 2024, from https://www.businesswire.com/news/home/20240523089601/en[12] Our Pipeline. Retrieved May 23, 2024 from https://www.icellgene.com/our-pipeline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