CD11a

DSMB approval to proceed to second cohort of REGALS trial (T Regulatory Cells for ALS). Ongoing Phase 1/1b study evaluating safety and efficacy of CK0803 (Neurotrophic T regulatory cells) HOUSTON, Feb. 19, 2024 /PRNewswire/ -- Cellenkos® today announced encouraging safety data from its innovative CK0803 neurotrophic T regulatory (Treg) cell therapy, being developed to help treat individuals with Amyotrophic Lateral Sclerosis (ALS). The company can now begin treating the second group of patients in the trial (clinicaltrials.gov: NCT05695521) The company was given the green light to move ahead following a review of safety data by the Data Safety Monitoring Board (DSMB). The DSMB found none of the participants experienced any serious adverse events or dangerous side effects from the therapy. "We are very excited and encouraged by this development," says Tara Sadeghi, Chief Operating Officer of Cellenkos. "This recommendation from the DSMB is an important step in bringing this potential disease modifying therapy to the patients and takes us closer to our ultimate goal of curing ALS." CK0803 is a neurotrophic, allogeneic, umbilical cord blood-derived T regulatory (Treg) cell therapy that preferentially homes towards inflamed microglia, developed by using Cellenkos' proprietary CRANE® technology, to generate disease-specific products. The completion of cohort 1 dosing allows for the continued enrollment on the Phase 1 Safety Run-in Study, to be followed by a Phase 1b Randomized, Double Blind, Placebo Control Trial of CK0803 in patients with ALS. The treatment will include four weekly infusions followed by five monthly infusions. Regulatory T Cells for Amyotrophic Lateral Sclerosis (REGALS) is a multicenter study including Columbia University, New York; Michael E. DeBakey VA Medical Center, Houston and Baylor College of Medicine, Houston. The primary objective of this study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients. This study will also provide preliminary efficacy data of CK0803 in ALS using the primary endpoint of combined assessment of function and survival (CAFS) that ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and secondary endpoint of longitudinal measurement of neurofilament light chain levels in serum and cerebrospinal fluid (CSF). About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. Majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. In a small (approximately 10%) of cases, ALS is caused by a mutation in a known ALS-associated gene. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. About CK0803 CK0803 is a novel allogeneic cell therapy product consisting of T regulatory cells, with a high cell surface expression of CD11a, that leverage CXCR3/CXCL10 axis to engage with the inflamed microglia. CK0803 is derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos' proprietary CRANE® process. There is no requirement for HLA or ABO matching of CK0803 to the recipient. Multiple doses of CK0803 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use, at the point of care, which makes it an ideal therapy that can be infused intravenously, in the outpatient setting. About Cellenkos®, Inc. Cellenkos is a clinical-stage biotechnology company located in Houston, Texas, USA, dedicated to the development and commercialization of the allogeneic, "off-the-shelf" cell-based products for the treatment of rare inflammatory diseases and autoimmune disorders. Cellenkos' T regulatory cells (Tregs) are derived from umbilical cord blood and as such are naïve, bonafide suppressor cells that do not require HLA or ABO matching and resolve inflammation through multiple direct and indirect mechanisms. Cellenkos' proprietary CRANE® process allows for tailoring of Tregs to become disease specific. Cellenkos' current clinical portfolio includes CK0801 (bone marrow failure); CK0802 (COVID ARDS); CK0803 (ALS) and CK0804 (myelofibrosis). For more information, please visit . Contact: Stacy Minor [email protected] SOURCE Cellenkos, Inc.

First cohort of REGALS (T Regulatory Cells for ALS) has been completed. Ongoing Phase 1/1b study evaluating safety and efficacy of CK0803 (Neurotrophic T regulatory cells). HOUSTON, Jan. 19, 2024 /PRNewswire/ -- Michael E. DeBakey VA Medical Center announces opening of a new clinical trial using CK0803- off-the-shelf, allogeneic T regulatory cells that have been modified to target neuroinflammation to treat the fatal neurodegenerative disease – Amyotrophic Lateral Sclerosis (ALS). Continue Reading ALS Clinical Coordinator Richel Aliboso, NP, Principal Investigator Dr. James Orengo and Study Coordinator Michelle Espiritu are thrilled to enroll Houston VA Veterans into this groundbreaking clinical trial. "We are very excited to open this first-in-class, best-in-class, cell therapy aimed to resolve neuroinflammation which fuels the ALS disease process. We believe that this novel approach of calming the inflamed microglia in the brain and spinal cord holds the promise for halting this relentlessly progressing disease", said Dr. James Orengo, principal investigator at the Michael E. DeBakey VA Medical Center and Assistant Professor of Neurology at Baylor College of Medicine. "Specifically, we are thrilled that our veterans will get the opportunity to receive such a cutting edge therapeutic that could be life altering. The incidence of ALS is elevated in Veterans and novel therapies are desperately needed. We are proud to be the first and only VA hospital in the nation to be part of this multi-center study". Please click here for the VA announcement. ALS is a rare, rapidly progressing and fatal neurodegenerative disorder that affects approximately 55,000 people globally. People with ALS experience muscle weakness, loss of movement, and difficulty breathing and swallowing, resulting in a severely declining quality of life and eventually death. The incidence of ALS has been rising in the veteran population and is a large unmet need. More than 16% of patients with ALS are veterans1. There are many health issues that veterans are at increased risk of, including ALS2. Veterans are twice as likely to be diagnosed with ALS than people who haven't served in the military3. "There is an urgent need for novel treatments for all forms of ALS, a devastating disease that affects far too many patients and their families. We made a conscious decision to make this novel cell therapy available to the veterans and remain committed to provide our continued support to those who have served our country," said Tara Sadeghi, Cellenkos' chief operating officer. "Leveraging our experience in consistently developing and manufacturing, robust, T regulatory cell therapies that are targeted towards disease specific mechanism of action and our intimate connection to the ALS patient community, Cellenkos made the decision to advance CK0803 to the clinic and, ultimately, to the market because we believe we are uniquely positioned to make it available to patients living with ALS." The first cohort of phase 1/ 1b CK0803 trial has been completed and is currently open for enrollment at Columbia University, New York, NY, led by PI, Dr Neil Shneider, M.D., Ph.D., director of Columbia University's Eleanor and Lou Gehrig ALS Center. About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. The majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. In a small (approximately 10%) of cases, ALS is caused by a mutation in a known ALS-associated gene. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. About CK0803 CK0803 is a novel allogenic cell therapy product consisting of T regulatory cells, with a high cell surface expression of CD11a, that leverage CXCR3/CXCL10 axis. CK0803 is derived from clinical-grade umbilical cord blood units and manufactured using Cellenkos' proprietary CRANE® process. There is no requirement for HLA or ABO matching of CK0803 to the recipient. Multiple doses of CK0803 can be manufactured from a single umbilical cord blood unit, where the final cryopreserved product is readily available for use, at the point of care, which makes it an ideal therapy that can be infused intravenously, in the outpatient setting. About Cellenkos®, Inc. Cellenkos is a clinical-stage biotechnology company located in Houston, Texas, USA, dedicated to the development and commercialization of the allogeneic, "off-the-shelf" cell-based products for the treatment of rare inflammatory diseases and autoimmune disorders. Cellenkos' T regulatory cells (Tregs) are derived from umbilical cord blood and as such are naïve, bonafide suppressor cells that do not require HLA or ABO matching and resolve inflammation through multiple direct and indirect mechanisms. Cellenkos' proprietary CRANE® process allows for tailoring of Tregs to become disease specific. Cellenkos' current clinical portfolio includes CK0801 (bone marrow failure); CK0802 (COVID ARDS); CK0803 (ALS) and CK0804 (myelofibrosis). For more information, please visit . Contact: Stacy Minor [email protected]. SOURCE Cellenkos, Inc.

☝ 点击上方 一键预约 ☝   最新最热的医药健康新闻政策眼科疾病的患者人数越来越多，其中干眼症和近视在我国有很多患者人群，今年年初大爆剧“狂飙”中高启强被诊断为干眼症，让更多人熟知这一疾病，干眼症听起来不像是很吓人的“绝症”，但是这个病不仅对患者生活质量产生负面影响，甚至可导致永久性视力损害，不容小视。据预计到2030年，国内干眼症药物市场规模将大幅增长至67亿美元，市场前景广阔，药物需求巨大。干眼症是经过诊断的由于泪液分泌减少或泪液蒸发过多造成眼睛干涩的一种疾病，其治疗药物有多种。人工泪液是最常用也是最基础的干眼症眼药水，随着技术的发展，更安全有效的环孢素类药物越来越受到重视，国内很多药企通过引进、仿制或者自研等方式纷纷加入布局环孢素类干眼症药物，其中兴齐药业的兹润是国内首款上市的环孢素仿制药。除此之外，临床上还在开发很多新机制的干眼症药物，包括今年5月上市的全氟己基辛烷Miebo、临床III期的TRPM8激动剂AR-15512和临床II期新一代的LFA-1拮抗剂VVN-001等。01市场规模大 增速快随着电子产品的普及和老龄化加剧等原因，眼科疾病发病率越来越高，眼部疾病主要有眼部炎症、青光眼、白内障、视疲劳、近视眼和干眼症等，其中屈光不正、干眼症的患者基数最大。干眼症，又称为角结膜干燥综合征，是经过诊断的由于泪液分泌减少或泪液蒸发过多的眼睛干涩的一种疾病，患病原因有多种，如过度依赖电子产品、空气污染、长期化眼妆、戴隐形眼镜和维生素A缺乏导致的眼睛干涩等。据《国人干眼多中心大数据报告》数据，目前中国干眼症患者约有3.6亿人，每年可能新增10%，经常使用视频终端者干眼发病率高达93%，佩戴隐形眼镜患者患病率高达90%，干眼正在成为继近视眼之后又一国民用眼健康问题。眼科技术壁垒比较强，国外的渗透率更高，近些年来，随着人们的重视，眼科领域得到快速发展，国内干眼症药物的市场规模逐渐增大，预计到2030年，干眼症药物市场规模将按28.4%的复合年增长率大幅增长至67亿美元。02治疗药物分类及盘点干眼症治疗手段主要包括药物治疗和非药物治疗。干眼症治疗药物可分为三大类：1. 人工泪液和促泌剂等，可以润滑眼表和促进修复；2. 抗菌药，针对感染相关或脂质异常型干眼症；3. 抗炎药物，靶向干眼症核心病理炎症机制[1]。表1. 部分获批或在研的干眼症药物NO.1人工泪液人工泪液已成为干眼症治疗的基础用药，起到可替代人体泪液的作用，通常是一类水溶性的高分子聚合物，滴到眼睛局部起到对眼睛黏膜舒缓和润滑作用，从而缓解眼睛干涩的症状，有眼药水和眼药膏两种形式。国内市场上人工泪液主要有玻璃酸钠、透明质酸和重组牛碱性成纤维细胞生长因子眼用制剂等，其中玻璃酸钠眼用制剂是目前医院市场销售规模最大的干眼症眼药水，市场占比超25%，其次是透明质酸眼用制剂和重组牛碱性成纤维细胞生长因子眼用制剂，分别占比约为25.8%和25.6%。不过，近两年玻璃酸钠和透明质酸在医院销售额呈现下滑态势，而重组牛碱性成纤维细胞生长因子眼用制剂如亿胜生物的贝复舒则呈上升趋势。目前，国内市面上在售的人工泪液有：SYSTANE® ULTRA（思然）、Refresh plus（亮视）、爱丽、润洁、润舒、贝复舒（含重组人成纤维生长因子）、泪然和大正制药爱丽丝人工泪目等。人工泪液与人体产生的泪液还是有所不同，大多数品种的人工泪液眼药水含有防腐剂，经常、频繁使用会伤害角膜，所以最好在医生指导下使用。NO.2免疫抑制剂（环孢素滴眼液）环孢素滴眼液在眼科的应用十分广泛，但不同浓度的环孢素滴眼液有不同的用途，国内目前已上市的环孢素滴眼液主要有三个品种：1.  主要用于预防和治疗眼角膜移植术后的免疫排异反应的1%环孢素滴眼液（3 mL:30 mg）；2. 主要用于治疗4岁及以上儿童和青少年的严重性春季角结膜炎（VKC）的0.1%环孢素滴眼液（Ⅲ）（0.3 mL:0.3 mg）；3. 主要用于干眼症患者的0.05%环孢素滴眼液（Ⅱ）（0.4 mL:0.2 mg）。 环孢素滴眼液是目前治疗干眼症最为有效的药物，且已经成为美国干眼症领域最为畅销的药品。全球已有多款环孢素滴眼液获批上市，如艾尔建（Allergan）的Restasis眼用乳剂0.05% 、太阳制药的Cequa 0.09%纳米胶束和参天的Ikervis阳离子银用乳液制剂0.1%等（图2）。除了原创新药外，全球也有很多环孢素仿制药获批上市，如迈兰的环孢素眼用乳剂0.05%以及国内首个获批上市的兴齐眼药的三类仿制药0.05%环孢素滴眼液（兹润）（图2）。表2. 全球获批上市的环孢素滴眼液除了兴齐眼药之外，国内也有很多企业在开发环孢素滴眼液，如兆科眼科、康哲药业、和铂医药和恒瑞医药等，致力于改进现有药物的环孢素活性、提升环孢素浓度，加速产品落地进程。表3. 部分在研环孢素滴眼液产品SHR8028滴眼液SHR8028滴眼液是由恒瑞医药从德国Novaliq公司授权引进的CyclASol®（0.1%环孢素A制剂）药物，CyclASol® 是一种由不溶于水的活性药物成分环孢霉素溶解在新型无水赋形剂全氟丁基戊烷中制成的，CyclASol®原研药已于今年6月份被FDA批准上市，SHR8028的药品上市许可申请于2023年3月20日获NMPA受理，用于治疗干眼的体征和症状。环孢素纳米胶束溶液康哲药业的环孢素纳米胶束溶液是引进自太阳制药的0.09%环孢素滴眼液，太阳制药的环孢素滴眼液于2018年在美国获批上市，不过，在2021年5月Sun Pharma在美国主动召回一批0.09%环孢素滴眼液，基于此，康哲药业决定主动暂停中国III期桥接试验，待收到符合公司质量要求的新批次试验用产品后，再启动桥接试验。环孢素A眼用凝胶除了滴眼液之外，兆科眼科正在开发公司自研的2.2类改良型新药环孢素A眼用凝胶，2022年6月8日，它的新药上市申请获国家药监局CDE受理，并且今年1月国家药监局通过该环孢素A眼用凝胶的药品注册及完成临床试验现场核查，并核实了环孢素A研发过程以及第III期临床试验中的原始记录及数据，向着最终注册及商业化迈进。NO.3LFA-1拮抗剂LFA-1（淋巴细胞功能相关抗原-1）属于β2家族整合蛋白，由αL(CD11a)和β2(CD18)亚单位组成的整合素，对白细胞向炎症局部移行以及淋巴细胞归巢和再循环起重要作用。Xiidra滴眼液Xiidra滴眼液是由Shire（于2019年1月被武田制药收购）开发的一款用于治疗干眼症的LFA-1拮抗剂，可以通过阻止T细胞粘附到ICAM-1，抑制细胞因子的分泌，最终防止炎症发生来治疗干眼症，2016年获FDA批准上市。2019年5月，诺华支付34亿美元的前期款项从武田制药获得该药物全球经营权，未来达到特定销售额时还将支付19亿美元的里程碑款。Xiidra在2022年为诺华制药带来了4.87亿美元的销售额，显示出成为重磅产品的潜力。今年6月30日，诺华以高达25亿美元与博士伦达成合作协议，将包括干眼症药物Xiidra在内的眼科药物转让给博士伦，剥离出了其眼科管线。VVN001VVN001是由维眸自主研发的全新、强效的第二代LFA-1抑制剂。去年VVN001在美国的临床II期试验取得积极结果：在完成84天治疗期后，5%治疗组的下方角膜荧光染色较基线的改善明显高于对照组。在总角膜荧光染色中，相对于溶媒组，VVN001治疗组具有明显的临床意义和统计学意义，并呈现了良好的剂效和时效关系。基于美国的临床试验结果，VVN001（5%）将在中国和美国开展关键性III期临床试验。NO.4全氟己基辛烷类药物：Miebo（NOV03）Miebo（NOV03）是由博士伦和Novaliq合作开发的一款全氟己辛烷滴眼液，它是一种半氟化烷烃，通过在泪膜上形成一层膜来减少泪液蒸发，于今年5月被FDA批准上市用于治疗与干眼病相关的过度眼泪蒸发，成为FDA批准的唯一一种专门针对泪液过度蒸发的药物。此次批准是基于两项为期57天，多中心、随机、双掩蔽，盐水对照研究GOBI和MOJAVE的结果，这些研究共招募了1,217名具有干眼病病史和睑板腺功能障碍（MGD）临床症状的患者。研究结果显示，Miebo达到其主要临床体征和患者报告的症状终点[2]。恒瑞医药2019年11月从Novaliq公司引进了该干眼病药物NOV03（SHR8058滴眼液），并且在今年2月它的上市申请获NMPA受理，用于治疗睑板腺功能障碍相关干眼症。03小结随着老龄化、工作压力的加剧以及电子产品的普及，用眼过度成为越来越普遍的现象，眼科疾病发病率越来越高，其中我国干眼症患者人数越来越多。目前，国内干眼症的药物治疗主要是人工泪液，随着技术的发展，越来越多新机制的更好的干眼症药物在研发中，全球已有环孢素滴眼液、LFA-1拮抗剂和全氟己基辛烷类药物上市，临床上在开发的新机制药物更多，期待后续有更安全有效的干眼症药物获批上市，药渡将带你持续关注。（来源:药渡  作者:五月)药闻康策新媒体矩阵微信公众号点击下方  一键关注  【免责声明】1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、收藏、点赞、点在看