APANECA: A Prospective, Parallel-arm, Multi-Surgeon Study of Cryopreserved AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (2024-E002-C)

The purpose of this study is to assess the safety and efficacy of cryopreserved AURN001 in patients with corneal edema secondary to endothelial dysfunction.

开始日期2024-09-16

申办/合作机构

Aurion Biotech, Inc.

NCT06041256

/ Active, not recruiting临床1/2期

CLARA: A Phase 1/2 Multi-center, Randomized, Double-Masked, Prospective, Parallel-Arm Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1)

The goal of this clinical trial is to compare different doses of AURN001 in patients with corneal edema secondary to corneal endothelial dysfunction. The main questions the clinical trial aims to answer are whether AURN001 effective and safe. Participants will receive a single injection of AURN001. A comparison between low, medium, and high doses of AURN001 against the contribution of each element, cells alone and Y27632 alone, will be conducted to determine the effects on corneal edema.

开始日期2023-10-18

申办/合作机构

Aurion Biotech, Inc.

NCT05309135

/ Completed临床1期

A Phase 1, Double-Masked, Randomized, Safety and Efficacy, Single Center Clinical Evaluation of Corneal Injection for Endothelial Dysfunction Using Human Corneal Endothelial Cell Therapy (HCEC-1) in Adult Subjects With Corneal Edema Secondary to Endothelial Dysfunction

The purpose of this study is to assess the safety of a fixed dose of human corneal endothelial cells when administered with varying concentrations of Rho kinase inhibitor (Y-27632) in patients with corneal edema secondary to endothelial dysfunction.

开始日期2022-03-24

申办/合作机构

Aurion Biotech, Inc.

100 项与 Neltependocel 相关的临床结果

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100 项与 Neltependocel 相关的转化医学

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100 项与 Neltependocel 相关的专利（医药）

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913

项与 Neltependocel 相关的文献（医药）

2025-03-01·JOURNAL OF BIOSCIENCE AND BIOENGINEERING

Formation of epithelial polarity on the fluorinated-oil microdroplet surface by regulating cell adhesion

Article

作者: Sonoi, Rie ; Kamihira, Masamichi

Polarized epithelial cells are compartmentalized into apical and basement membranes with asymmetrically distributed proteins. This study aimed to establish a method for culturing epithelial cells at the fluorinated oil (Novec-7500) microdroplet surface for the formation of epithelial polarity, which is desirable for regenerative medicine and drug discovery research. Microdroplet surfaces treated with fibronectin, which regulates a variety of cell behaviors through direct interactions with cell surface integrin receptors, were prepared for culturing epithelial cells. The cells adhered rapidly to the fibronectin-coated fluorinated oil-medium interface and reached confluence. However, as the culture time progressed, the cells began to detach from the microdroplet surface. To promote adhesion to the microdroplet interface, the cells were exposed to the Rho-associated protein kinase inhibitor Y27632, which increased the frequency of microdroplets with cells adhering to the liquid-liquid interface by 1.63-fold. However, continuous exposure to Y27632 caused the cells to detach from the microdroplet surface. When the drug was switched from Y27632 to forskolin, which enhances cell-cell and cell-substrate adhesion, the cells remained as a monolayer on the microdroplet interface. Na⁺/K⁺-ATPase and zonula occludens-2 were localized to the apical and lateral membranes of the cells, respectively, while paxillin co-localized with fibronectin at the microdroplet interface. This suggests that the cells exhibited epithelial polarity. These findings indicate that the regulation of cell-cell and cell-substrate adhesion is crucial for establishing epithelial polarity in cells cultured on the microdroplet interface.

2025-02-18·BRITISH JOURNAL OF DERMATOLOGY

Novel therapeutic strategy for intractable keloids: suppression of intracellular mechanotransduction and actin polymerization via Rho-kinase pathway inhibition

Article

作者: Lee, Mihyun ; Park, Jun Ho ; Park, Ji-Ung ; Hwang, Joseph ; Min, Sally ; Kim, Ki-Myo

Abstract:

Background:

Keloid is a dermal fibrotic disorder characterized by excessive extracellular matrix production by fibroblasts. Despite the significance of mechanostimulation in fibrotic diseases, its association with keloid pathophysiology or treatment remains unexplored.

Objectives:

To investigate the role of mechanical force in keloid formation and elucidate the significance of Rho-associated coiled-coil-containing kinase 1 (ROCK1) as a mechanoresponsive target for keloid treatment.

Methods:

Patient-derived keloid fibroblasts (KFs) were subjected to cyclic stretching ranging from 0% to 20% elongation using a cell-stretching system. We observed the inhibitory effects of the ROCK1 inhibitor Y27632 on KFs and keloid formation. Validation was performed using a keloid xenograft severe combined immune-deficient (SCID) mouse model.

Results:

ROCK1 was overexpressed in KFs isolated from patients. Cyclic stretching induced fibroblast proliferation and actin polymerization by activating Rho/ROCK1 signalling. Treatment with Y27632 downregulated fibrotic markers reduced the migration capacity of KFs and induced extensive actin cytoskeleton remodelling. In the keloid xenograft SCID mouse model, Y27632 effectively suppressed keloid formation, mitigating inflammation and fibrosis.

Conclusions:

The ROCK1 inhibitor Y27632 is a promising molecule for keloid treatment, exerting its effects through actin cytoskeleton remodelling and nuclear inhibition of fibrotic markers in keloid pathogenesis.

2025-02-01·INTERNATIONAL IMMUNOPHARMACOLOGY

CD271 regulates osteogenic differentiation of ectomesenchymal stem cells via the RhoA/ROCK signaling pathway

Article

作者: Zou, Yanhui ; Jin, Haoyang ; Cheng, Gu ; Ye, Jiaqi ; Zhang, Jiajun ; Nie, Xin ; Wang, Keyu ; Zeng, Xiaoke ; Zhao, Yeke

The low-affinity neurotrophic receptor CD271 plays a crucial role in the osteogenic differentiation of ectomesenchyme stem cells (EMSCs), which is essential for the development and regeneration of jaw bones. This study aimed to investigate the influence of CD271 on EMSCs osteogenic differentiation and to uncover the underlying mechanisms. CD271-deficient mice exhibited delayed mandibular bone development, with a significantly reduction in the expression of osteogenic makers such as ALP, Col-1, OPN, and RUNX2. Single-cell sequencing further proved that the RhoA/ROCK signaling pathway was downregulated in CD271^ExIII-/- EMSCs, highlighting the potential role of CD271 in regulating the osteogenic differentiation of EMSCs. After treatment with Pentanoic Acid or Y27632, the protein expression of Runx2 and Col-1 in EMSCs was either enhanced or reduced, respectively. These findings suggest that CD271 facilitates the osteogenic differentiation of EMSCs in vitro and contributes to mandibular alveolar bone formation in vivo through activation of the RhoA/ROCK signaling pathway.

项与 Neltependocel 相关的新闻（医药）

2025-03-27

·FierceBiotech

Alcon gains upper hand in Aurion power struggle via majority stake, removing CEO

Alcon has replaced Aurion Biotech\'s CEO Greg Kunst “effective immediately.”\n Eye care giant Alcon appears to have gained the upper hand in the ongoing power struggle with Aurion Biotech by securing a majority stake in the clinical-stage company and replacing its CEO.The move will see Aurion \"operate as a separate company with full support from Alcon to advance its clinical-stage allogeneic cell therapy asset, AURN001, into phase 3 for corneal edema secondary to corneal endothelial disease during the second half of 2025,” an Alcon spokesperson told Fierce Biotech.As part of the transaction, Alcon said in a March 26 release that it has promoted Aurion Chief Scientific Officer Arnaud Lacoste, Ph.D., to replace Greg Kunst as CEO “effective immediately.”The two companies have been locked in a struggle for months over Aurion’s desire to list on the New York Stock Exchange. Alcon’s subsidiary Alcon Research, which is an investor in Aurion, tried to block the IPO plans in court, arguing that its rights were being violated by Aurion’s plans to go public. Aurion countersued, claiming that the investor was trying to trap the biotech so it could buy Aurion at a low price. In late January, a judge determined that Alcon’s consent was not required for an Aurion IPO, writing that the investor’s “argument is illogical in light of the parties’ contractual scheme.” At the time, Alcon said it would appeal.On one point raised by the lawsuit, regarding Alcon’s ability to vote its full share of the 40% ownership stake it has had in Aurion since October 2024, the judge backed Alcon, saying the company “has the right to vote its full block of stock.” Deerfield Management, another one of Aurion’s investors, came to the biotech\'s defense last month. The firm sued Alcon to stop what it described as “an unrelenting campaign to take over Aurion” at a cheaper price.Deerfield’s intervention was triggered by what the firm called a “Valentine’s Day massacre,” where Alcon had entered into an agreement to buy Aurion stock from fellow investor Petrichor Opportunities Fund on Feb. 14, a move that would give Alcon a majority of voting shares. Later that day, Aurion\'s executive chair of the board Thomas Frinzi resigned, and Petrichor and Alcon swapped out a Petrichor board appointee for an Alcon designee, which resulted in Alcon holding three of six total board seats, according to the suit.Deerfield and Alcon both invested in Aurion as part of a $120 million series C round Deerfield led in 2022. Aurion’s focus is on regenerative therapies for eye diseases, and its lead candidate is a cell therapy for corneal edema secondary to endothelial dysfunction, a disease that currently requires invasive specialty surgery to treat.Deerfield declined to comment to Fierce yesterday about what Alcon’s newfound majority stake in Aurion means for the more recent litigation. Aurion had not responded to Fierce’s request for comment at time of publication.

高管变更细胞疗法

2025-03-27

·抗体圈

全球药企创新力榜单揭榜，这些“新”值得关注

近日，商业媒体《快公司》（Fast Company）对2024年全球最具创新力的医药公司进行梳理总结，10家药企为此前研发进展甚微的疾病推出突破性疗法，并推动现有疗法可及性。疗法涉及阿尔茨海默病（AD）、精神分裂症、血友病、癌症等多领域。 ARS公司肾上腺素开启鼻喷时代当前，治疗过敏性休克的唯一疗法是肾上腺素，长期以来仅可通过注射给药。但有不少患者无法及时接受注射，甚至因针头过大而犹豫不决。2024年8月，ARS公司的肾上腺素鼻喷雾剂Neffy获美国FDA批准上市。据悉，该药的喷雾容器无需预热，只需插入并按下，且在高达122°F（50℃）的温度下其保质期为30个月。这比自动注射器有很大优势，后者保质期为18~20个月，且对温度的要求更严格。 BMS 精分新机制药物绽放 2024年9月，FDA批准百时美施贵宝（BMS）的Cobenfy成为几十年来首个治疗精神分裂症的主要新药。Cobenfy的使用机制与现有治疗方法完全不同，通过触发毒蕈碱受体而不是多巴胺受体起作用，是首个通过这种方式治疗精神分裂症的药物。 Cobenfy在临床试验中总体耐受性良好，与常用的非典型抗精神病药物不同，没有关于某些老年患者死亡率增加的黑框警告。 BMS目前正在努力扩大该药的适应症：可能会在2026年公布该药治疗AD的试验数据，还计划针对双相情感障碍Ⅰ型和AD适应症启动另外3项Ⅲ期试验。礼来 AD疗法新秀善补短板 2024年7月，FDA批准了礼来的AD药物Kisunla上市，这是一种用于治疗早期AD症状的单克隆抗体。Kisunla由礼来开发，是首个也是唯一一个使用有限给药疗程靶向清除淀粉样斑块的疗法。在1736名患者的Ⅲ期试验中，与安慰剂相比，Kisunla在18个月时将认知和功能衰退减缓了35%，并将疾病进展到下一临床阶段的风险降低了39%。 Kisunla与其竞争对手，即百健和卫材的Leqembi相比，给药间隔更长。前者每4周给药一次，后者每2周给药一次。除了AD领域创新，礼来还继续巩固其利润丰厚的GLP-1产品Mounjaro和Zepbound的市场地位。该公司于2024年1月推出了直接面向消费者的渠道，以折扣价提供Zepbound处方药，并提供送货上门服务。礼来也在不断扩大GLP-1药物适应症，例如在2024年12月23日，FDA批准减肥药Zepbound成为首个专门用于治疗阻塞性睡眠呼吸暂停的处方药，据估计，该病影响超过2200万名美国人。 Aurion公司细胞治疗预防失明该公司的Vyznova于2023年5月在日本获批，并于2024年9月在日本上市，是首个经过临床验证的角膜护理细胞疗法。Vyznova用于治疗角膜内皮疾病（如大泡性角膜病变），这是一种影响全球数百万人的渐进性疾病，如果不及时治疗，会导致失明。在Vyznova之前，大泡性角膜病变的唯一治疗方法是使用供体组织进行角膜移植，但每70只患病眼睛中，只有1个供体角膜可用，数量稀少。Aurion公司开发了一种制造工艺，可以从单个供体的角膜内皮细胞中生产多达1000剂Vyznova。 2024年6月，FDA授予Vyznova突破性疗法认定和再生医学先进疗法认定，为该细胞疗法提供了快速审批途径。2024年12月公司发布的美国Ⅰ/Ⅱ期临床试验数据显示，其最高剂量可显著改善视力。 Iovance公司冲破实体瘤治疗壁垒 2024年2月，FDA加速批准Iovance公司的Amtagvi用于治疗晚期黑色素瘤（正在进行Ⅲ期试验）。Amtagvi是首个获批用于治疗实体瘤的一次性个体化T细胞疗法。据悉，目前CAR-T细胞疗法虽然对血液肿瘤较为有效，但在实体瘤中表现不佳。Amtagvi是一种一次性疗法，使用肿瘤浸润淋巴细胞（TIL），持久治疗更多实体瘤。 Amtagvi获批使TIL疗法有望成为治疗实体肿瘤的新型药物。目前，该药正在进行肺癌、宫颈癌等临床试验。这种一次性疗法每位患者的费用为51.5万美元（未扣除返款和折扣）。该公司预计，许多保险公司将以与CAR-T细胞疗法相同的水平纳入对应报销范围。 Adaptimune公司滑膜肉瘤患者获新希望 2024年8月，Adaptimmune公司工程化T细胞疗法Tecelra获FDA加速批准。该药用于治疗之前接受过化疗的特定类型滑膜肉瘤成人患者。这项批准使Tecelra成为美国批准的首个针对实体瘤癌症的自体T细胞免疫疗法，也是十多年来首个针对滑膜肉瘤的新治疗选择。滑膜肉瘤是一种罕见的软组织癌，最常见于年轻人。2024年12月，公司宣布第一位患者已接受了治疗。该疗法定价为727,000美元，在美国癌症细胞药物中每剂成本最高。该公司第二款在研T细胞疗法lete-cel已在Ⅱ期试验达到主要终点。公司估计，这两种疗法结合可在美国市场产生4亿美元的销售额年峰值。 Verona公司畅通慢阻肺呼吸通道 2024年6月，FDA批准Verona公司慢性阻塞性肺病（COPD）疗法Ohtuvayre上市，用于成人患者。该疗法是20多年来治疗该病的首个具有新型作用机制的吸入维持疗法，有望为美国约1600万患有COPD的成年人带来新治疗选择。 Ohtuvayre是一种单一小分子药物，具有独特的双重作用机制，可选择性抑制磷酸二酯酶3/4（PDE3/4），同时增强支气管扩张（打开肺部小气道）并减少与COPD相关的炎症，无需使用类固醇。据悉，该公司目前正在进行Ohtuvayre的Ⅱ期临床试验，用于治疗其他有未满足医疗需求的呼吸系统疾病，包括慢性非囊性纤维化支气管扩张、囊性纤维化和哮喘。辉瑞释放血友病前沿产品活力 2024年10月，FDA批准了辉瑞的Hympavzi上市，这是首个每周注射一次的药物，用于预防或减少患有A型血友病（缺少凝血因子Ⅷ）和B型血友病（缺少凝血因子Ⅸ）成人和12岁及以上儿童患者的出血发作频率。在其他治疗领域，辉瑞已进军抗体药物偶联物（ADC）市场，2024年4月，FDA全面批准了Tivdak，该药物此前已于2021年获得加速批准，用于治疗复发性或转移性宫颈癌患者。 ImmunityBio公司 IL-15受体激动剂攻克膀胱癌多达40%的非肌层浸润性膀胱癌（NMIBC）患者对传统的免疫疗法（即卡介苗，BCG疗法）没有反应。2024年4月，FDA批准了ImmunityBio公司的Anktiva上市，是对BCG无应答的NMIBC患者的首创疗法和罕见突破。Anktiva被批准用于与标准护理BCG疗法联合进行维持治疗，以提高疗效。 Anktiva的作用方式新颖，其为一种IL-15受体激动剂，可激活自然杀伤（NK）和T细胞攻击肿瘤和癌细胞。2024年第三季度，Anktiva创造了约600万美元的净产品收入。据公司披露，截至2024年11月，已有100名患者接受了Anktiva-BCG联合疗法治疗，完全缓解率为71%。Anktiva在对检查点抑制剂无反应的非小细胞肺癌患者中进行的Ⅱ期试验数据显示，中位总生存期几乎是标准化疗的2倍。 Zevra公司小分子药穿越血脑屏障 2024年9月，FDA批准了Zevra公司的小分子口服药物Miplyffa与酶稳定剂miglustat联用，治疗C型尼曼匹克病（NPC）。NPC是一种极为罕见的遗传性疾病，会导致进行性神经系统症状和器官功能障碍。Miplyffa是FDA批准的首个用于治疗成人和2岁及以上儿童NPC相关神经系统症状的药物，可穿越血脑屏障。 NPC会阻止人体对细胞中的胆固醇和其他脂质的使用，进而导致这些物质在体内病理性积累。该疾病会对患者的言语、认知、吞咽、运动和精细运动技能造成损害，患有该疾病的人平均寿命约为13年。来源：From cancer vaccines to COPD treatments,these 10 companies are developing innovative medicines，FAST COMPANY 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

突破性疗法临床3期上市批准临床结果细胞疗法

2025-03-27

·BioPharmaDive

Alcon buys majority stake in IPO-seeking cell therapy startup Aurion

The leading eye-care company Alcon on Wednesday said it has acquired a majority stake in Aurion Biotech, capping months of legal wrangling over the future of the cell therapy developer.As part of the takeover, Aurions board appointed Chief Scientific Officer Arnaud Lacoste as the companys new CEO, immediately replacing Greg Kunst. Aurion will continue as a separate company, with full support from Alcon, according to Wednesdays press release.Aurion is focused on diseases that affect the endothelium, the layer of cells on the posterior surface of the cornea. Using cell therapy, the company aims to reverse vision loss and offer patients an easier recovery than treatments that involve corneal endothelial transplant procedures. Aurion has an approved product in Japan and is advancing another, AURN001, in Phase 1/2 research in the U.S.The company had generated interest among investors, raising $120 million in a 2022 financing led by Deerfield Management that included participation from Alcon. As Aurion looked for further funding, Alcon expressed interest in buying the company, but its offer was rejected, according to court documents. Aurion then made plans to go public.Alcon, however, was already a top shareholder and sued to block Aurions IPO, losing in court in January. Deerfield also sued Alcon, saying Alcon was trying to thwart the IPO so it could buy Aurion itself at a discount. Independent analyses placed a multibillion-dollar value on Aurion even before it launched its first product in Japan and completed a clinical trial in the U.S., Deerfield said.For more than two years, Alcon has waged an unrelenting campaign to take over Aurion at a highly discounted valuation, Deerfield alleged. Alcon has sought to cut off Aurions ability to obtain financing from sources other than Alcon.As of February, Alcon held about 40.5% of Aurion and Deerfield held about 34%, according to Deerfields lawsuit. Alcons statement on Wednesday made no mention of the planned IPO. An Aurion spokesperson declined to comment to BioPharma Dive. Officials at Alcon and Deerfield didnt immediately respond to requests for comment.In Alcons release, new Aurion CEO Lacoste said his company looks forward to leveraging Alcons global resources and commercial expertise to move AURN001 into Phase 3 development later this year. The Phase 1/2 study included 97 patients with corneal edema secondary to corneal endothelial dysfunction. '

细胞疗法临床3期高管变更临床结果

100 项与 Neltependocel 相关的药物交易

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研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
大疱性角膜病变	日本	Aurion Biotech, Inc.	2023-03-17

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
内皮功能障碍	临床2期	萨尔瓦多	Aurion Biotech, Inc.	2024-09-16
角膜水肿	临床2期	美国	Aurion Biotech, Inc.	2023-10-18
角膜水肿	临床2期	加拿大	Aurion Biotech, Inc.	2023-10-18

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06041256 (CLARA, BusinessWire) 人工标引	临床1/2期	角膜水肿	97	AURN001: 1.0 × 10^6 neltependocel + 100 μM Y-27632 (high cell dose)	廠願鹹簾遞醖鑰鹹遞鹽(繭範積壓醖鹹窪網網顧) = 構廠膚築遞餘餘簾窪遞鬱壓鏇醖遞鏇膚壓鹽憲 (蓋窪窪膚淵艱範鹽蓋餘 )	积极	2024-12-18
				AURN001: 5.0 × 10^5 neltependocel + 100 μM Y-27632 (medium cell dose)	-