This is a non-interventional long-term follow-up study of patients who have participated in LogicBio studies for the treatment of MMA and received hLB-001

开始日期2022-07-20

申办/合作机构

LogicBio Therapeutics, Inc.

[+1]

NCT04581785 / Terminated临床1/2期

A Phase 1/2 Open-label Clinical Study of hLB-001 Gene Therapy in Pediatric Patients With Methylmalonic Acidemia Characterized by MMUT Mutations

The SUNRISE trial is a first-in-human (FIH), open-label, Phase 1/2 clinical trial designed to assess the safety, tolerability and preliminary efficacy of a single intravenous infusion of hLB-001 in pediatric patients with MMA characterized by methylmalonyl-CoA mutase gene (MMUT) mutations. hLB-001 is a liver-targeted, recombinant engineered adeno-associated viral (rAAV) vector utilizing the LK03 capsid (rAAV-LK03), designed to non-disruptively integrate the human methylmalonyl-CoA mutase gene at the albumin locus.
The trial is expected to enroll pediatric patients with ages ranging from 6 months to 12 years, initially starting with 3 to 12 year-old patients and then adding patients aged 6 months to 2 years.

开始日期2021-05-29

申办/合作机构

LogicBio Therapeutics, Inc.

[+1]

100 项与 LB-001 相关的临床结果

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100 项与 LB-001 相关的转化医学

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100 项与 LB-001 相关的专利（医药）

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项与 LB-001 相关的文献（医药）

2014-06-01·Gut

LB-001 Suppressor Of Cytokine Signalling 3 (socs3) Impacts On Intestinal Epithelial Cell Proliferation During Intestinal Helminth Infection

Review

作者: Rachael Rigby ; Kathryn Else ; Elisabeth Shaw

Introduction In the murine model of whip worm infection Trichuris muris invades cecal and colonic epithelial cells and elicits either a Th1 (susceptible) or Th2 (resistant) immune response. An increase in intestinal epithelial cell (IEC) turnover has been implicated to aid in the physical expulsion of the worm in the resistant phenotype. 1 Failure to initiate a transient increase in IEC turnover can lead to chronic infection. SOCS3 limits IEC proliferation and its loss is associated with increased tumour growth and hyperproliferation in cancer and intestinal injury models. 2 SOCS3 may have an important role in regulating IEC in intestinal homeostasis and may mediate resistance to pathogens. This study aims to examine the role of SOCS3 in regulating IEC turnover in a murine model of T. muris infection. Methods SOCS3 expression was examined in the intestine of T. muris resistant or susceptible mice by immunohistochemistry and real-time PCR. SOCS3 IEC (villin cre) knockdown (SOCS3 fl/fl -VC) and control (SOCS3 fl/fl -WT) mice were infected with T. muris and intestinal tissue examined at 3, 12, 21 and 35 days after infection. Crypt depth was measured and cell proliferation rates determined using an EdU Click-iT assay. Worm burden and immune response was assessed at 35 days to determine outcome of infection. Results SOCS3 expression (mRNA and protein) was increased in the intestine of susceptible mice compared with resistant mice post T. muris infection. We hypothesised that increased SOCS3 may limit IEC turnover and therefore reduced SOCS3 expression may promote IEC proliferation and expulsion of parasites. At 35 days post-infection there was an increase in proliferation in cecal tissue from SOCS3 fl/fl -VC vs. SOCS3 fl/fl -WT mice. This supports an increase in cell turnover, as no concomitant change in crypt depth was observed. Examination of tissue from SOCS3 fl/fl -VC mice during the early stages of T. muris infection (days 3 and 12) showed little difference in crypt depth, proliferation or inflammation compared to control, suggesting that IEC SOCS3 impacts on crypt dynamics at >12 days post-infection. Evidence of T. muris infection was observed in both SOCS3 fl/fl -VC and SOCS3 fl/fl -WT mice at 35 days, but differences in worm burden and immune response remain to be determined. Conclusion Intestinal epithelial cell SOCS3 impacts on crypt dynamics during intestinal helminth infection. SOCS3 may play a role in susceptibility to intestinal parasites. Disclosure of Interest None Declared.

1991-02-12·Zentralblatt fur Veterinarmedizin. Reihe A

Serotonin Levels in the Hen Ovarian Follicles after Methallibure (I. C. I 33, 828) Treatment*

Article

作者: H. Paczoska-Eliasiewicz ; J. Rzαsa

Summary:

The purpose of the present study was to examine the effect of methallibure (MLB), a non‐steroid inhibitor of pituitary gonadotrophic activity on serotonin (5‐HT) levels in the wall of preovulatory follicles (F1 ‐ F4) in the domestic hen. 5‐HT was determined spectrofluorometrically.Hens were treated with MLB (10 mg/hen per os) twice a day for 3 successive days. 5‐HT was determined in F1‐F4 (Fl > F2 > F3 > F4) follicles of the control group, on the next day (MLB‐1 group) and 6 days following cessation of MLB administration (MLB‐6 group). During MLB treatment egg production was inhibited in all hens. In the MLB‐6 group, five hens out of seven took up egg laying on the sixth day after MLB administration. Within each examined group there were no significant differences in 5‐HT concentration between Fl ‐ F4 follicles. In comparison to the control, MLB caused a significant (P < 0.01 ‐ 0.05) increase of 5‐HT concentration in F1 (MLB‐1 group) and F4 (both MLB‐groups).The results obtained indicate that there is a relationship between pituitary activity and 5‐HT levels in the preovulatory follicles of the domestic hen.

PloS one

Novel AAV-mediated genome editing therapy improves health and survival in a mouse model of methylmalonic acidemia

Article

作者: Chiang, Kyle ; Wu, Carmen ; Amarwani, Shreya ; Walsh, Noel ; McCarthy, Elizabeth ; Drouin, Lauren ; Zhang, Xiaohan ; Xiong, Qiang ; Chau, B Nelson ; Gordo, Susana ; Zhang, Shengwen ; Vora, Jenisha ; Frank, Dylan ; Ramesh, Nikhil ; Ko, Chih-Wei ; Hebben, Matthias ; Bastille, Amy ; Liao, Jing

Methylmalonic acidemia (MMA) is an inborn error of metabolism mostly caused by mutations in the mitochondrial methylmalonyl-CoA mutase gene (MMUT). MMA patients suffer from frequent episodes of metabolic decompensation, which can be life threatening. To mimic both the dietary restrictions and metabolic decompensation seen in MMA patients, we developed a novel protein-controlled diet regimen in a Mmut deficient mouse model of MMA and demonstrated the therapeutic benefit of mLB-001, a nuclease-free, promoterless recombinant AAV GeneRideTM vector designed to insert the mouse Mmut into the endogenous albumin locus via homologous recombination. A single intravenous administration of mLB-001 to neonatal or adult MMA mice prevented body weight loss and mortality when challenged with a high protein diet. The edited hepatocytes expressed functional MMUT protein and expanded over time in the Mmut deficient mice, suggesting a selective growth advantage over the diseased cells. In mice with a humanized liver, treatment with a human homolog of mLB-001 resulted in site-specific genome editing and transgene expression in the transplanted human hepatocytes. Taken together, these findings support the development of hLB-001 that is currently in clinical trials in pediatric patients with severe forms of MMA.

项与 LB-001 相关的新闻（医药）

2023-07-28

·Pharma Manufacturing

Alexion buys Pfizer preclinical gene therapy portfolio for $1B

AstraZeneca's rare disease business Alexion has into a definitive purchase and license agreement with Pfizer for a portfolio of preclinical gene therapy programs and enabling technologies. According to the agreement, Alexion will acquire and license Pfizer's early-stage rare disease gene therapy portfolio for a total amount of up to $1 billion. Alexion will also pay tiered royalties on sales as part of the arrangement. The portfolio acquired includes preclinical gene therapy programs and innovative technologies, such as novel adeno-associated virus (AAV) capsids. AAV capsids have proven to be effective in delivering therapeutic gene cargo for gene therapy and gene editing. By leveraging these resources with their existing capabilities and the recent acquisition of LogicBio, Alexion is hoping to develop and advance next-generation genomic medicines. AstraZeneca's Alexion acquired LogicBio Therapeutics last year in a deal worth $68 million, aiming to rare disease treatments by utilizing LogicBio's technology platforms for gene therapy. LogicBio's research has focused on developing genetic medicine for pediatric patients with rare diseases, and they recently received FDA clearance to proceed with phase 1/2 trials for LB-001, a potential single-administration treatment for methylmalonic acidemia.

引进/卖出并购基因疗法临床研究

2023-03-15

·BioSpace

OncoNano Medicine to Present at the American Association for Cancer Research (AACR) Annual Meeting 2023

SOUTHLAKE, Texas--(BUSINESS WIRE)-- OncoNano Medicine, Inc. today announced three poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023 at the Orange County Convention Center, Orlando, Florida. Presentation Overview: TITLE: Improved tolerability and tumor specific delivery of a therapeutic bispecific T cell engager using a pH-sensitive nanoparticle platform PRESENTER: Qingtai Su, Ph.D. DATE: April 16, 2023 TIME: 1:30 – 5:00 PM ET SECTION and PRESENTATION NUMBER: Poster Section 30, No. 815 TITLE: Encapsulation of IL-12 with an ultra pH-sensitive nanoparticle platform improves tolerability and promotes antitumor response in mice PRESENTER: Tian Zhao, Ph.D. DATE: April 16, 2023 TIME: 1:30 – 5:00 PM ET SECTION and PRESENTATION NUMBER: Poster Section 34, No. LB001 TITLE: ONM-501, a dual-activating polyvalent STING agonist, enhances tumor retention and demonstrates favorable preclinical safety pro > PRESENTER: Zirong Chen, Ph.D. DATE: April 18, 2023 TIME: 1:30 – 5:00 PM ET SECTION and PRESENTATION NUMBER: Poster Section 34, No. LB245 About OncoNano Medicine OncoNano Medicine is developing a new class of products that utilize principles of molecular cooperativity in their design to exploit pH as a biomarker to diagnose and treat cancer with high specificity. Our product candidates and interventions are designed to help patients across the continuum of cancer care and include solid tumor therapeutics, agents for real-time image guided surgery and a platform of immune-oncology therapeutics that activate and guide the body’s immune system to target cancer. OncoNano’s lead development candidate is pegsitacianine, a novel fluorescent nanoprobe using the ONBOARD platform, that is currently under study in Phase 2 clinical trials as a real-time surgical imaging agent for use in multiple cancer surgeries. ONM-501, OncoNano’s second development program, is a next generation STING (STimulator of INterferon Genes) agonist that is advancing towards a first in human trial in the first half of 2023. Pegsitacianine and ONM-501 have been supported by grants received from the Cancer Prevention Research Institute of Texas. Learn more at .

临床2期AACR会议免疫疗法

2023-01-04

·美通社

北海康成已完成基因疗法管线整合

已从马萨诸塞州立大学Chan医学院(UMass Chan Medical School)获得治疗脊髓性肌萎缩症(SMA)的潜在同类最佳基因疗法的全球独家授权。已完成两种溶酶体贮积症的基因疗法的技术转让。北京和马萨诸塞州伯灵顿 2023年1月4日 /美通社/ -- 北海康成制药有限公司（以下简称“ 北海康成 ”，股票代码1228.HK）是一家在中国领先并专注罕见疾病及肿瘤领域的全球化的生物制药公司，致力于创新疗法的研究、开发和商业化。公司宣布已从马萨诸塞州立大学Chan医学院获得开发、生产和商业化治疗脊髓性肌萎缩症(SMA)的新型第二代基因疗法的全球独家授权。 2022年在美国基因与细胞治疗学会(ASGCT)、欧洲基因与细胞治疗学会(ESGCT) 及世界肌肉学会年会上发表的动物数据显示，在通过静脉注射治疗SMA小鼠模型中，该基因疗法在多个关键终点上表现优于基准疗法，且表现出更少的肝脏毒性。基准疗法中所使用的载体与世界上唯一获批的治疗SMA的基因疗法的载体相似。北海康成赞助了该项研究，并将继续评估这一新型基因疗法与目前的标准治疗方案相比可能具有的额外优势。此外，北海康成宣布已完成LogicBio® Therapeutics用于治疗法布雷病和庞贝氏病而开发的基因治疗产品的全部技术转让。根据修订后的协议，北海康成保留了基于肝靶向腺相关病毒(AAV)衣壳sL65的法布雷病和庞贝氏病基因疗法项目的全球独家许可。北海康成还取得LogicBio用于法布雷病和庞贝氏病基因疗法专有制造工艺的非独家全球授权。此外，新协议不再保留原始协议中公司获得的可研发基于sL65的针对另外两个适应症基因疗法的选择权以及对大中华区的LB-001（一种甲基丙二酸血症的研究性疗法）的选择权。北海康成制药有限公司的创始人、董事长兼首席执行官薛群博士表示：“我们与马萨诸塞州立大学医学院共同开发了这一有望成为治疗SMA的同类最佳基因疗法，并且拥有该疗法的全球权利。此外，我们在马萨诸塞州伯灵顿开设的北海康成新一代创新技术研发中心也已经投入运营。我们将积极开发治疗包括SMA、法布雷病及庞贝氏病在内的罕见病的潜在同类最佳基因疗法，以改善这些疾病的治疗选择非常有限的现状。” Penelope Booth Rockwell生物医学研究教授、微生物与生理系统教授、红瑞(Horae)基因治疗中心主任和李伟波罕见病研究所联席所长高光坪博士表示：“新型hSMN1 AAV基因治疗载体由内源性SMN1启动子和密码子优化的人源SMN1基因组成，与基准载体相比，其疗效和安全性有明显改善，从而支持对该疗法的进一步临床开发。我们对北海康成开发这一脊髓性肌萎缩症基因疗法的能力充满信心，并希望通过该疗法最终可以帮助到更多遭受此灾难性疾病折磨的患者和家庭。” 关于第二代基因疗法新型第二代基因疗法(scAAV9-SMN1p-co-hSMN1)是一种在内源性启动子控制下表达密码子优化的人源SMN1基因的自互补AAV9基因疗法。在小鼠脊髓性肌萎缩症(SMA)模型研究中，与静脉给药的基准基因疗法相比，第二代疗法表现出更长的寿命、更好的运动功能恢复和更完整的神经肌肉接头神经支配，而没有基准载体所见的肝脏毒性。基准载体与已获批准的SMA基因疗法中使用的载体相似，在巨细胞病毒增强子(cytomegalovirus enhancer)及鸡β－肌动蛋白(chicken β-actin)启动子驱动表达人源SMN1 基因，以便在所有细胞类型中普遍表达，与基准载体不同的是，第二代基因疗法载体采用了内源性SMN1 启动子控制在不同组织的基因表达的策略。有关数据在2022年的美国基因和细胞治疗学会(ASGCT)、欧洲基因与细胞治疗学会(ESGCT)及世界肌肉学会年会上公布。该基因疗法由北海康成开发，用于治疗脊髓性肌萎缩症。北海康成拥有全球独家开发、生产和商业化的权利。关于脊髓性肌萎缩症(SMA) 脊髓性肌萎缩症(SMA)是一种由缺乏功能性运动神经元存活基因1(SMN1)引起的罕见遗传性疾病。该基因编码为运动神经元存活所必需的蛋白质，缺乏则会导致运动神经元快速且不可逆的损伤，从而引起衰弱性运动功能丧失，在大多数情况下可导致死亡。最常见的SMA1 在出生至6 个月期间发病，占SMA病例的60%（根据Cure SMA）。如不治疗，SMA1会导致进食及呼吸困难，或在两岁前死亡。SMA2 在出生6 至24 个月期间发病。患者即使能够自行坐立，也将无法行走，30%的患者在25岁前死亡(Cure SMA)。SMA3和SMA4则属更为罕见、发病较晚的疾病类型，在儿童期至成年早期发病，也会导致运动功能丧失及死亡。根据spinalmuscularatrophy.net的资料，全世界每6,000至10,000名新生儿中，就有一名SMA患者。目前，已获批的SMA治疗方案有限。即使近期有新方案获批，仍存在大量未满足的医疗需求。北海康成制药有限公司简介北海康成制药有限公司（以下简称「北海康成」，股票代码1228.HK）是一家在中国领先并专注罕见疾病领域的全球化的生物制药公司，致力于创新疗法的研究、开发和商业化。公司目前拥有13个具有可观市场潜力的药物资产组合，其中包括三种已获批上市产品和10 个在研药物。这些产品均针对一些较普遍的罕见疾病和罕见肿瘤适应症，比如亨特综合征和其他溶酶体贮积症、补体介导的疾病、血友病A、代谢紊乱、罕见的胆汁淤积性肝病、神经肌肉疾病以及胶质母细胞瘤。北海康成的新一代基因技术研发中心实验室正在开发针对罕见遗传病，包括庞贝氏症、法布雷病、脊髓性肌萎缩症(SMA)和其他神经肌肉疾病的新型及潜在治愈性的基因疗法，并与世界领先的研究人员和生物技术公司合作。来自SMA基因治疗的动物数据已在美国基因和细胞治疗学会(ASGCT)、欧洲基因和细胞治疗学会(ESGCT)以及世界肌肉组织大会上发表。公司的全球合作伙伴包括不限于Apogenix、GC Pharma、Mirum、药明生物、Privus、UMass Chan医学院、华盛顿大学医学部和Scriptr Global等。如需了解更多关于北海康成制药有限公司的资讯，请访问： www.canbridgepharma.com 前瞻性声明本文中作出的前瞻性陈述仅与本文作出陈述之日的事件或信息有关。除非法律要求，否则我们不承担公开更新或修改任何前瞻性陈述的义务，无论是由于新信息、未来事件或其他原因，在做出陈述的数据之后或反映意外事件的发生情况。您应完整阅读本文，并了解我们未来的实际结果或表现可能与我们的预期存在重大差异。在本文中，我们或我们的任何董事或我们公司的意图的陈述或引用均在本文发表之日作出。这些意图中的任何一个都可能随着未来的发展而改变。

基因疗法细胞疗法

100 项与 LB-001 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
甲基丙二酸血症	临床2期	美国	Alexion Pharmaceuticals, Inc.	2021-05-29

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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


NCT04581785 (147 \| SUNRISE, CTgov)	临床1/2期	甲基丙二酸血症	4	hLB-001 (Cohort 1 Part A: 3- to 12-years Old)	壓齋齋範簾鹽餘選觸構(餘獵窪壓顧壓積鏇網觸) = 壓艱鏇廠築構鑰顧壓顧簾簾範鬱願淵簾襯餘築 (繭積窪膚襯淵壓鏇窪醖, 醖獵積廠獵廠顧夢憲醖 ~ 廠構獵網遞齋鏇窪糧襯) 更多	-	2024-02-23
				hLB-001 (Cohort 1 Part B: 6- to 36-months Old)	壓齋齋範簾鹽餘選觸構(餘獵窪壓顧壓積鏇網觸) = 齋艱餘願餘積艱鹽鹽壓簾簾範鬱願淵簾襯餘築 (繭積窪膚襯淵壓鏇窪醖, 願顧鹽醖壓齋鏇壓鏇鹽 ~ 壓範獵繭獵簾鑰夢膚選) 更多