A multiple-ascending-dose (MAD), randomized, placebo-controlled, blinded trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Elafin in healthy adult subjects. The purpose of this study is to assess Elafin that is being developed for treatment of PAH. Elafin inhibits elastase, an enzyme that is increased in pulmonary hypertension and is a major factor in the development of PAH. Elafin will be administered subcutaneously daily for 7 days in normal healthy subjects followed over a 28 day time period.

开始日期2019-03-18

申办/合作机构

Stanford University

[+3]

EUCTR2008-000938-49-DE

/ Not yet recruitingN/A

Placebo-controlled Randomized Trial to evaluate the Effect of Elafin on Cytokine Profiles after Major Surgery - Phase II - Elafin

开始日期2008-08-18

申办/合作机构-

100 项与 Tiprelestat(Proteo Biotech AG) 相关的临床结果

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100 项与 Tiprelestat(Proteo Biotech AG) 相关的转化医学

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100 项与 Tiprelestat(Proteo Biotech AG) 相关的专利（医药）

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项与 Tiprelestat(Proteo Biotech AG) 相关的文献（医药）

2025-05-08·Beneficial Microbes

Production of human elafin by genetically modified Lactococcus lactis: evaluation of its anti-inflammatory effects in a murine model of intestinal mucositis

Article

作者: Langella, P. ; LeBlanc, J.G. ; Gontier, S. ; Bermúdez-Humarán, L.G. ; Levit, R. ; de Moreno de LeBlanc, A. ; Aucouturier, A.

Abstract:

The aim of this study was to develop a recombinant strain of Lactococcus lactis designed to produce human elafin, a serine protease inhibitor, through a Stress-Inducible Controlled Expression (SICE) System, and to evaluate its anti-inflammatory potential both in vitro and in vivo. The impact of this recombinant strain on the efficacy of 5-Fluorouracil (5-FU) was evaluated by in vitro assays with Caco-2 (human colonic cancer cells) and IEC-18 (non-cancerous intestinal cells) exposed to 5-FU with or without the recombinant bacterium. In vivo, a mouse model of intestinal mucositis (IM) was induced by daily injections of 5-FU, followed by oral administration of the recombinant strain twice daily. Key assessments included the occurrence of diarrhea, small intestinal morphology and histopathology, and serum cytokines levels. In vitro results showed that the elafin-producing strain enhanced 5-FU cytotoxicity against Caco-2 cells, while preserving IEC-18 cell viability in the presence of 5-FU. In vivo, the strain significantly reduced the occurrence of diarrhea, improved the villus height/crypt depth ratio and attenuated intestinal inflammation. In addition, the recombinant strain reduced serum levels of the pro-inflammatory cytokines IL-6 and TNF-α, while significantly increasing the anti-inflammatory cytokine IL-10. Importantly, the strain did not compromise the anti-cancer efficacy of 5-FU on tumor cells and protected non-cancer cells. These results confirm the in vivo anti-inflammatory effects of this elafin-producing strain against IM.

2024-12-31·Hematology (Amsterdam, Netherlands)

Diagnostic and prognostic role of elafin in skin acute graft versus host disease: a systematic review

Review

作者: Bhandari, Pragya ; Abu Serhan, Hashem ; Barboza, Joshuan J. ; Neupane, Raksha ; Yadav, Rukesh ; Sah, Ranjit ; Paudel, Sunil ; Sah, Sanjit ; Shah, Sangam ; Bhattarai, Abhinav ; Dhakal, Garima

BACKGROUND AND OBJECTIVE:

Graft versus host disease (GVHD) is the common complication seen after allogeneic hematopoietic stem cell transplantation (HSCT) and a pleomorphic syndrome that resembles autoimmune and other immunologic disorders, leading to profound immune dysregulation and organ dysfunction. The most common targets of GVHD are skin, gastrointestinal tract and liver. GVHD is classified as acute graft versus host disease (aGvHD) if it occurs within the first 100 days after HSCT and chronic graft versus host disease(cGVHD) if it occurs after day 100. The skin is most frequently and earliest affected by aGvHD, followed by the gastrointestinal tract and liver. An ideal biomarker would predict the onset and severity of clinical acute GVHD and help to direct management, and this is an area of active research regarding the use of biomarkers for diagnosis and prognosis of acute GVHD. Recently, elafin has been identified as a potential plasma biomarker for aGVHD.

METHOD:

We searched the databases PubMed, Cochrane library, and medRxiv for all studies investigating the Diagnostic or prognostic role of elafin in GVHD. We set the search strategy incorporating the search terms, 'elafin', 'graft versus host', and 'GVHD', and operated using the Boolean operators 'AND', and 'OR'. Thus, retrieved articles were then exported on an Excel® sheet, and duplicates were removed. The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel version. The quality assessment of the included studies was determined using the QUIPS tool.

RESULT:

The search revealed 547 studies and 6 studies that met the eligibility criteria of this review have been included. The major finding of our study is the significant elevation of elafin in skin aGVHD.

CONCLUSION:

Elafin is a significant biomarker for diagnosis and prognosis of skin aGVHD and should be assessed within 2 weeks of the onset of the disease.

2024-09-20·MICROBIOLOGY-SGM

Use of Rgg quorum-sensing machinery to create an innovative recombinant protein expression system in Streptococcus thermophilus

Article

作者: Balvay, Aurélie ; Langella, Philippe ; Mézange, Christine ; Bermúdez-Humarán, Luis G. ; Monnet, Véronique ; Juillard, Vincent ; Maillot, Nathanael Jean ; Honvo-Houeto, Edith ; Gardan, Rozenn ; Rabot, Sylvie

Streptococcus thermophilus holds promise as a chassis for producing and secreting heterologous proteins. Used for thousands of years to ferment milk, this species has generally recognized as safe (GRAS) status in the USA and qualified presumption of safety (QPS) status in Europe. In addition, it can be easily genetically modified thanks to its natural competence, and it secretes very few endogenous proteins, which means less downstream processing is needed to purify target proteins, reducing costs. Extracellular degradation of heterologous proteins can be eliminated by introducing mutations that inactivate the genes encoding the bacterium’s three major surface proteases. Here, we constructed an inducible expression system that utilizes a peptide pheromone (SHP1358) and a transcriptional regulator (Rgg1358) involved in quorum-sensing regulation. We explored the functionality of a complete version of the system, in which the inducer is produced by the bacterium itself, by synthesizing a luciferase reporter protein. This complete version was assessed with bacteria grown in a chemically defined medium but also in vivo, in the faeces of germ-free mice. We also tested an incomplete version, in which the inducer had to be added to the culture medium, by synthesizing luciferase and a secreted form of elafin, a human protein with therapeutic properties. Our results show that, in our system, protein production can be modulated by employing different concentrations of the SHP1358 inducer or other SHPs with closed amino acid sequences. We also constructed a genetic background in which all system leakiness was eliminated. In conclusion, with this new inducible expression system, we have added to the set of tools currently used to produce secreted proteins in S. thermophilus, whose myriad applications include the delivery of therapeutic peptides or proteins.

项与 Tiprelestat(Proteo Biotech AG) 相关的新闻（医药）

2024-12-17

·医药速览

Nature┃ALDH4A1 是一种被保护性抗体靶向的动脉粥样硬化自身抗原

研究背景心血管疾病（CVD）是全球主要的致死原因，其中心肌梗死和中风导致的死亡占绝大多数。动脉粥样硬化是血栓形成和心血管事件的主要根本原因，它是一种慢性炎症性疾病，往往在长期内无明显症状。目前，该领域对于有效的治疗和诊断方法的需求十分迫切。动脉粥样硬化斑块中含有自身抗体，揭示了动脉粥样硬化与自身免疫反应之间的联系。尽管如此，对于动脉粥样硬化过程中自身抗体反应的免疫学机制及其影响的认识仍然有限。数十年前，研究者首次在动脉粥样硬化斑块中检测到抗体，而在动脉粥样硬化的发展过程中，B细胞和抗体免疫反应被认为具有既保护又致病的双重作用。然而，关于这些反应的潜在抗原触发因素及其对动脉粥样硬化的具体影响的知识仍然不足，因为大多数研究都集中于氧化特异性新表位（OSE），例如氧化低密度脂蛋白（oxLDL）。 2020年10月，来自西班牙马德里国家心血管研究中心的Cristina Lorenzo教授团队在Nature（IF:50.5）杂志上发表了题为：“ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies”的研究论文。在本研究中研究团队对动脉粥样硬化相关的抗体库进行了深入的高通量单细胞分析，并针对来自动脉粥样硬化易发的Ldlr−/−（低密度脂蛋白受体缺失）小鼠以及对照组小鼠的超过1700个B细胞进行了抗体基因测序。这项工作揭示了56种由体内扩增的B淋巴细胞克隆在动脉粥样硬化背景下表达的抗体，这些抗体中有三分之一能够与动脉粥样硬化斑块发生反应，发现病变中的多种抗原能够激发抗体响应。进一步的深度蛋白质组学分析发现了一种动脉粥样硬化相关自身抗体A12的靶抗原ALDH4A1——一种涉及脯氨酸代谢的线粒体脱氢酶。在动脉粥样硬化的发展过程中，ALDH4A1的分布会发生变化，且在患有动脉粥样硬化的小鼠和人类中，循环ALDH4A1的水平会增加，这支持了ALDH4A1作为疾病生物标志物的潜力。研究团队进一步将A12抗体注入Ldlr−/−小鼠体内，发现这能够延缓斑块的形成，并降低循环中的游离胆固醇和低密度脂蛋白水平。主要成果 ●研究揭示了动脉粥样硬化斑块中含有自身抗体，并且有多种抗原可以触发抗体反应。 ●通过基于质谱的蛋白质组学分析发现了ALDH4A1（一种线粒体脱氢酶，参与脯氨酸代谢）是动脉粥样硬化相关自身抗体A12的靶抗原。 ●ALDH4A1具有作为动脉粥样硬化生物标志物的潜力。 ●A12抗可以延缓斑块的形成，并减少循环中的游离胆固醇和低密度脂蛋白（LDL），暗示抗ALDH4A1抗体可能对抗动脉粥样硬化的进展，并可能在心血管疾病（CVD）治疗中具有潜力。研究设计 1. 动物模型的选择与处理：使用了两种小鼠模型：Ldlr−/−（低密度脂蛋白受体缺陷）小鼠和对照小鼠。Ldlr−/−小鼠被喂食高胆固醇和高脂肪饮食（HFD），以诱导动脉粥样硬化的发展。对照组小鼠则被喂食正常饮食。 2. 单细胞抗体库的构建与分析：从Ldlr−/−和对照小鼠中分离出B细胞，特别是生发中心B细胞和浆细胞。利用单细胞基因排序和PCR扩增，对这些细胞的免疫球蛋白重链（IgH）和轻链（IgL）基因进行测序。 3. 抗体的克隆与表达：从测序数据中识别出56种由体内扩增的B细胞克隆表达的抗体。将这些抗体克隆到含有人类IgG1恒定区的表达载体中，并在体外表达这些抗体。 4. 抗体反应性分析：通过ELISA（酶联免疫吸附试验）和免疫荧光染色等方法，测试这些抗体对动脉粥样硬化斑块的反应性。识别出与动脉粥样硬化斑块反应的抗体，并进一步分析它们的特异性。 5. 靶抗原的鉴定：通过深度蛋白质组学分析，鉴定了ALDH4A1作为A12抗体的靶抗原。验证了A12抗体对ALDH4A1的特异性，并探讨了ALDH4A1在动脉粥样硬化中的作用。 6. 疾病生物标志物的评估：评估了循环中ALDH4A1的水平，作为动脉粥样硬化的潜在生物标志物。 7. 治疗潜力的探索：将A12抗体注入Ldlr−/−小鼠体内，观察其对动脉粥样硬化进展的影响。研究结果动脉粥样硬化与生发中心B细胞反应的增强有关探索动脉粥样硬化相关的抗体免疫反应时，采用了Ldlr-/-小鼠模型。这些小鼠在高胆固醇和脂肪饮食（HFD）的喂养下，会发展出动脉粥样硬化的病理特征。本文研究重点在于评估生发中心反应，这是一个B细胞在生发中心经历类别转换重组（CSR）和体细胞超突变（SHM）以产生多样化抗体，并最终分化为记忆B细胞和高亲和力浆细胞的过程（图1a，扩展数据图1a-c、2a、b）。结果观察到Ldlr-/-HFD小鼠它们逐渐积累了生发中心B细胞（Fas+GL7+）、T滤泡辅助细胞（TFH；CXCR5+PD1+）、记忆B细胞（PD-L2+）、IgG+转换B细胞以及表达kappa轻链的CD138+浆细胞或浆细胞。这种积累伴随着血浆中IgM和IgG水平的增加，以及针对低密度脂蛋白、丙二醛修饰（MDA）-LDL和HSP60的IgM抗体的积累（扩展数据图1d、e），这些现象在其他动脉粥样硬化模型中也有报道。为了深入分析动脉粥样硬化中的生发中心反应，作者对Ldlr-/- HFD小鼠和对照组小鼠的生发中心B细胞及浆细胞进行了高通量单细胞抗体复合物基因测序（扩展资料图2c）。从超过1700个B细胞中，作者获得了免疫球蛋白重链（IgH）和轻链（IgL）基因的配对序列（图1b，扩展数据图2d、e）。分析显示，Ldlr-/- HFD小鼠和对照组小鼠在可变区（V）和连接区基因（J）的使用以及CDR3（互补决定区第三环）长度上没有显著差异（扩展数据图2f-h），这表明两组小鼠中抗体多样性形成的基因重组过程是相似的。值得注意的是，Ldlr-/- HFD小鼠显示出抗体亚型分布的差异，其中IgG2亚型的比例较高，而IgG3亚型的比例较低（图1c、d），并且SHM负荷较高（图1e、f）。这些发现表明，动脉粥样硬化与生发中心B细胞反应的增强有关，这种增强特征为SHM负荷的增加和IgG2亚型的偏向性增强。图1 动脉粥样硬化过程中的抗体免疫反应扩展数据图1 动脉粥样硬化过程中的生殖中心反应和抗体产生扩展数据图2 通过单细胞测序和免疫球蛋白基因克隆鉴定动脉粥样硬化相关抗体体液免疫针对动脉粥样硬化斑块中的多种抗原为了探究动脉粥样硬化相关反应是否针对特定的靶抗原，研究者首先依据免疫球蛋白重链（H）和轻链（L）相同的V(D)J基因使用以及相同的免疫球蛋白重链CDR3长度，确认了体内扩增B细胞产生的抗体群（扩展数据图4a）。从Ldlr-/- HFD小鼠中筛选出代表30个抗体群的56种抗体进行表达（扩展数据图2c、3b）。作为对照，同样从正常饮食的野生型小鼠（Ldlr+/+ ND小鼠）的B细胞中克隆并表达了25种抗体（扩展数据图2c）。在Ldlr-/- HFD小鼠中，针对MDA-LDL、原生LDL和HSP60的抗体比例略高，尽管这一差异并不显著（扩展数据图3c）。在两组小鼠的抗体中，均未检测到多反应性（扩展数据图3d）。为了验证动脉粥样硬化相关抗体是否能识别斑块病变，对动脉粥样硬化小鼠的主动脉窦切片进行了免疫荧光染色。结果显示，从Ldlr-/- HFD小鼠克隆的抗体中有三分之一（18/56）对动脉粥样硬化斑块表现出反应活性，而从Ldlr+/+ ND小鼠克隆的抗体中仅有8%（2/25）表现出反应（图2a，扩展数据图4）。自身反应抗体展现出不同的斑块反应模式，这些模式与使用商用抗氧化LDL（oxLDL）抗体观察到的染色模式有所区别（图2b，扩展数据图4）。这些发现表明，在动脉粥样硬化过程中，体液免疫反应确实是针对动脉粥样硬化斑块中的多种抗原。图2 从动脉粥样硬化小鼠克隆出来的抗体对斑块的反应性扩展数据图3 克隆相关B细胞集群的分析扩展数据图4 来自Ldlr−/− HFD老鼠克隆抗体的斑块反应扩增抗体A12能够识别动脉粥样硬化过程中异常表达的抗原在深入探究动脉粥样硬化相关抗体反应的特异性时，研究者特别关注了抗体A12，它在Ldlr-/- HFD小鼠的主动脉窦中表现出强烈的斑块反应性。随着疾病的进展，A12的斑块反应性逐渐增强（图2b，c），且主要表现为细胞外反应（图2c，扩展数据图5a）。同样值得注意的是，与克隆相关抗体A8也展现出了强烈的斑块反应性。研究进一步发现，A12不仅在Ldlr-/- HFD小鼠的主动脉根部（扩展数据图5b）有染色，还在另一种动脉粥样硬化小鼠模型——ApoE缺失小鼠的主动脉（扩展数据图5c）中显示出染色。此外，在Ldlr-/- HFD小鼠的脾脏滤泡中也检测到了A12的染色（扩展数据图5d）。这一发现与从脾脏B细胞克隆出的A12反应相吻合，表明A12的靶抗原可能循环至脾脏或在脾脏表达，参与触发免疫反应。在肝脏切片的染色中，观察到在Ldlr-/- HFD动脉粥样硬化小鼠中，肝静脉周围的A12反应性增强并发生变化（扩展数据图5e），这表明A12抗原的分布或表达变化不仅限于动脉。尤为重要的是，A12与人类动脉粥样硬化病变也有反应（图2d）。因此，A12能够识别在小鼠模型和人类动脉粥样硬化过程中异常表达的抗原。扩展数据图5 A12抗体反应性的荧光染色分析 ALDHA1是A12的靶抗原并可引起T细胞依赖性抗原特异性免疫反应为了确定A12抗体的抗原特异性，研究者采用了A12抗体免疫沉淀Ldlr-/- HFD和Ldlr+/+ ND小鼠的主动脉总提取物，并随后进行了高通量质谱分析（图3a）。作为特异性对照，还分析了从动脉粥样硬化小鼠和对照小鼠身上克隆的其他抗体（A10、A11、D7CT、E9CT）以及与动脉粥样硬化无关的B1-8抗体的免疫沉淀物。A12抗体特异性地沉淀了醛脱氢酶4家族成员A1（ALDH4A1），这是一种位于线粒体基质中参与脯氨酸降解途径的脱氢酶（图3b，扩展数据图6a）。A12同样能在对照野生型主动脉中沉淀ALDH4A1（图3b，扩展数据图6a），这表明A12并不识别动脉粥样硬化氧化特异性新表位(OSE)。通过酶联免疫吸附试验（ELISA）、商用抗ALDH4A1抗体免疫印记法和竞争ELISA法，进一步证实了A12对ALDH4A1的特异性（图3c，扩展数据图6b，c）。商用抗ALDH4A1抗体对主动脉窦切片的染色显示，其斑块反应性与A12相似（扩展数据图6f）。此外，抗ALDH4A1抗体在Ldlr-/- HFD动脉粥样硬化小鼠肝静脉周围显示出与A12相同的反应模式（扩展数据图5e、6g）。值得注意的是，在Ldlr-/- HFD小鼠和Apoe-/- HFD小鼠的血浆中测得了高滴度的抗ALDH4A1抗体，而在对照组中却没有测到，这些抗体在动脉粥样硬化的进展过程中不断累积（图3d，扩展数据图6d，e）。此外，用ALDH4A1免疫野生型小鼠或Ldlr-/-小鼠会引发T细胞依赖性免疫反应和抗ALDH4A1 IgG1抗体的积累（扩展数据图7）。这些结果不仅确定了ALDH4A1是A12的靶抗原，而且表明ALDH4A1能够引发T细胞依赖性抗原特异性免疫反应，这种反应与血浆中高滴度抗ALDH4A1 IgG抗体的产生有关。图3 ALDH4A1是动脉粥样硬化中的一种B细胞自身抗原扩展数据图6 ALDH4A1自身抗原可被A1抗体识别，并与小鼠和人类的动脉粥样硬化相关扩展数据图7 ALDH4A1触发一种依赖于T细胞的B细胞反应 ALDH4A1具有作为动脉粥样硬化生物标志物的潜力在Ldlr−/− HFD小鼠模型中，观察到血浆中的ALDH4A1水平显著升高（图3e）。同样，在人体动脉粥样硬化组织中的ALDH4A1含量也被发现高于健康人的主动脉组织（扩展数据图6h）。此外，对一组颈动脉粥样硬化患者的分析显示，血浆中的ALDH4A1水平明显升高：在患者中，有23%（13/56）的人血浆ALDH4A1水平超过75纳克/毫升，而对照组个体中只有5%（3/54）（图3f）。这些患者的血浆ALDH4A1水平与动脉粥样硬化的存在密切相关，而与传统的风险因素和C反应蛋白（CRP）水平无显著关联（扩展数据图6i）。因此，循环中的高ALDH4A1水平与动脉粥样硬化的发病机制紧密相关，这表明ALDH4A1有潜力成为该疾病的一个生物标志物。抗ALDH4A1 A12抗体治疗可减缓动脉粥样硬化的进展并改善血脂状况为了探究A12抗体对动脉粥样硬化进程的影响，对Ldlr-/-高脂饮食（HFD）小鼠进行了为期12周的连续静脉注射。为了进行对照，同样给小鼠注射了PBS或B1-8 IgG2b同型对照抗体（图4a）。经过12周的高密度脂蛋白饮食和常规抗体治疗后，发现接受mA12-IgG2b治疗的小鼠相较于接受mB1-8-IgG2b对照抗体或仅PBS治疗的小鼠，其动脉粥样硬化斑块显著减小（图4b, c）。尽管未观察到斑块的细胞或胶原成分存在定性差异，但mA12-IgG2b治疗组小鼠的血浆中游离胆固醇和低密度脂蛋白水平较低（图4d, e）。特别值得注意的是，对经A12处理的小鼠肝脏进行的定量高通量蛋白质组分析揭示了与碳水化合物、氨基酸和脂质代谢以及免疫系统和炎症通路相关的蛋白质表达发生了特定变化（扩展数据图8a-c）。此外，非靶向脂质组学分析也显示出几种脂质代谢途径的变化，包括花生四烯酸（一种炎症介质的前体）代谢的调整和多种甘油三酯种类的减少（图4f，扩展数据图8d）。因此，蛋白质组学和代谢组学数据均表明，A12治疗对肝脏中的脂质代谢和免疫途径产生了显著影响，这可能与A12治疗小鼠体内观察到的全身脂质变化相关。这些结果表明，抗ALDH4A1 A12抗体治疗能够减缓动脉粥样硬化的进展并改善血脂状况。图4 输注 A12 可延缓 Ldlr-/- HFD 小鼠的动脉粥样硬化进展扩展数据图8 A12处理小鼠肝脏的高通量定量蛋白质组学研究总结文章研究成果揭示了A12抗体及其靶向的抗原ALDH4A1，它们分别作为动脉粥样硬化的潜在治疗和诊断工具。进一步鉴定本研究中识别的其他斑块反应性抗体的靶标，将深化对抗体在动脉粥样硬化中作用机制的理解。尽管ALDH4A1的免疫原性起源尚未明确，但有假设认为动脉粥样硬化引起的细胞损伤可能使ALDH4A1从其在细胞内的线粒体隐藏位置释放，这种分布或浓度的变化可能触发抗体反应。未来研究需要阐明A12是否通过清除受损组织中的ALDH4A1来发挥其在动脉粥样硬化中的保护作用。无论如何，研究结果表明ALDH4A1和A12是心血管疾病治疗领域具有潜力的临床工具。原文链接：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41586-020-2993-2 参考文献 Lorenzo C, Delgado P, Busse CE, Sanz-Bravo A, Martos-Folgado I, Bonzon-Kulichenko E, Ferrarini A, Gonzalez-Valdes IB, Mur SM, Roldán-Montero R, Martinez-Lopez D, Martin-Ventura JL, Vázquez J, Wardemann H, Ramiro AR. ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies. Nature. 2021 Jan;589(7841):287-292. doi: 10.1038/s41586-020-2993-2. Epub 2020 Dec 2. PMID: 33268892. 编译：Sail 校对：Evan Flle 排版：Sail 封面来源：Chatgpt 往期推荐 J.Infect∣北京地坛医院王雅杰教授团队联合国家蛋白质科学中心于晓波教授团队揭示真实世界新冠变异株感染人群的免疫系统进化规律 2024-11-07 旦生医学 | 工业化智能蛋白芯片技术助力新冠感染人群免疫力适应性进化研究再创突破 2024-10-18 Cell┃细胞外囊泡与颗粒标志物揭示泛癌图谱 2024-11-24 国际血浆蛋白质组计划2024年进展 2024-11-01 旦生医学 | 蛋白质芯片技术鉴定首个银屑病全周期无创检测标志物Elafin校准品获批临床注册 2024-10-09 旦生医学 | 工业化智能蛋白芯片助力新发传染病全周期应对能力建设 2024-09-16 往期链接 “小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学 | 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普 | 医药前沿笔记 PROTAC技术 | 抗体药物 | 抗体药物偶联-ADC 核酸疫苗 | CAR技术 | 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

2024-12-09

·PipelineReview

tiakis Biotech AG Reports Clinical Phase Ib/II Trial Results of Tiprelestat for the Treatment of Hospitalized COVID-19 Patients

Tiprelestat was safe and well tolerated, with initial signs of clinical efficacy KIEL, Germany I December 9, 2024 I tiakis Biotech AG , a clinical-stage biopharmaceutical company developing novel therapeutics for life-threatening pulmonary and cardiovascular diseases, today announced the results of its randomized, double-blind, placebo-controlled clinical Phase Ib/II COMCOVID trial evaluating Tiprelestat for the treatment of patients hospitalized due to COVID-19. In 2021, tiakis Biotech received support from the German Federal Ministry of Education and Research (“BMBF”) to initiate the COMCOVID trial. Tiprelestat (human recombinant Elafin) is an anti-inflammatory human protein and a reversible inhibitor of human neutrophil elastase and proteinase 3 as well as an inhibitor of the formation of neutrophil exosomes and neutrophil extracellular traps. The compound is in development as a potential therapeutic in diseases characterized by an adverse overreaction of innate immune responses, e.g., pulmonary arterial hypertension (PAH) or COVID-19. During the study period, tiakis had to adapt to changes in the COVID-19 pandemic, which led to a significant decrease in the rate of hospitalizations due to this disease. 17 patients could be recruited and treated (9 Tiprelestat, 8 placebo) until the end of the trial period. Even though the power of the small sample size of this study does not allow for a reliable efficacy assessment, it was decided to report all efficacy results. From an exploratory perspective, it is interesting to note that the number of days (mean ± SD) with any oxygen support (i.e. COVID-19 WHO-CPS ≥5 score points) was lower in the Tiprelestat group (2.4 ± 3.6 days) compared to placebo (4.0 ± 6.2 days). In addition, the number of days with relevant renal issues after day 1 was zero in the Tiprelestat group (0 ± 0) compared to the placebo group (1.5 ± 4.2). Consistent with previous clinical trials, the results regarding adverse events, clinical laboratory parameters and vital signs demonstrate that Tiprelestat was safe and well tolerated when administered via infusion in a multiple dose regimen over 7 days. In addition, results of pharmacokinetic evaluation show that Tiprelestat does not accumulate in blood plasma. “Although the trial did not reach the targeted patient number and we cannot draw a reliable conclusion on efficacy, the data reinforce our confidence in the safety profile of Tiprelestat, indicating that it can be administered repeatedly without significant adverse effects in this patient population aged up to 89 years and suffering from a severe inflammatory lung disease,” said Dr. Michael Dreher, Professor of Medicine / Pneumology and Head of the Department of Pneumology and Intensive Care Medicine at the University Hospital Aachen, Germany, and lead medical investigator of the COMCOVID trial. “The solid safety and supportive data in such a diverse and vulnerable patient population will strengthen the development of Tiprelestat in other pulmonary diseases. I would like to thank all our colleagues and partners for their fantastic work under such challenging and unprecedented pandemic conditions,” added Martin Voss, CEO of tiakis Biotech AG. The summary of the clinical study report is publicly available in the German Registry for Clinical Trials ( https://drks.de/search/en/trial/DRKS00031463 ). About tiakis Biotech tiakis Biotech AG is an innovative, clinical-stage pharmaceutical company specializing in groundbreaking approaches to protect human tissues and organ structures. The Company develops anti-inflammatory treatments to prevent severe organ damage and failure, particularly after invasive surgeries, with a primary focus on pulmonary arterial hypertension (PAH). tiakis´ lead candidate Tiprelestat is in clinical development and addresses unmet medical needs in life-threatening conditions. The Company is based in Kiel, Germany. For further information, please visit https://tiakis.bio. SOURCE: tiakis Biotech

临床结果临床研究

2023-05-16

·BioSpace

tiakis Biotech AG and Northway Biotech: Successful Tech Transfer and Expansion of Manufacturing Capabilities for Tiprelestat

KIEL, GERMANY / ACCESSWIRE / May 16, 2023 / tiakis Biotech AG (tiakis), in collaboration with its CDMO partner Northway Biotech, is pleased to announce the successful completion of a technology transfer and ramp-up of manufacturing capabilities for Tiprelestat, a pioneering anti-inflammatory and tissue-protective drug being developed for the prevention of postoperative inflammatory complications following major surgery, treatment of COVID-19 and pulmonary arterial hypertension. For the first time worldwide, a clinical trial is being supported by Tiprelestat study material produced at an industrial fermentation scale, representing a ten-fold increase in manufacturing potential to 3,000 L. tiakis Biotech AG and Northway Biotech collaboration tiakis Biotech AG and Northway Biotech: Successful Tech Transfer and Expansion of Manufacturing Capabilities for Tiprelestat "The marked increase in manufacturing capabilities lays the foundation for the next stage of tiakis' development programs, with the recent start of our COMCOVID phase Ib/II clinical trial being a prime example," said Martin Voss, tiakis Biotech AG co-CEO. The enhanced production capabilities is a result of the successful completion of a technology transfer and subsequent ramp-up program, achieved in a short time through close collaboration with end-to-end biologics CDMO Northway Biotech, based in Vilnius, Lithuania. Reflecting on this milestone, Vladas Algirdas Bumelis, CEO of Northway Biotech, stated: "The confidence our partners have placed in our two-decade-long expertise has enabled us to collaboratively scale up the process and meet tiakis' deadlines. Our state-of-the-art 3,000 L stainless-steel fermenter train was utilized to carry out the implementation successfully. We extend our sincere well-wishes to our partners as they move forward with their innovative drug through clinical trials, and we look forward to future collaborations." André Markmann, VP Business Development of Northway Biotech, added: "This partnership exemplifies our commitment to assist our partners in achieving their objectives by leveraging our technical expertise and operational capabilities. We are immensely proud to be part of this groundbreaking project, which addresses a significant unmet medical need." By attaining this pharmaceutical and technological milestone, tiakis and Northway Biotech have demonstrated their capabilities to pave the way towards groundbreaking achievements as pioneers in their respective fields. The success of this fast-paced project is characterized by strong collaborative interaction, mutual trust, and flexibility between the two companies. About Tiprelestat tiakis biopharmaceutical drug candidate Tiprelestat promises an excellent therapeutic benefit-risk pro use as an anti-inflammatory and tissue-protective drug. Tiprelestat is identical to the human protein elafin with high specificity for tissue-destroying and inflammation-promoting proteases. The development program of Tiprelestat is focused on the late-stage development of Tiprelestat in major surgery and early-stage development in pulmonary arterial hypertension (PAH) and COVID-19. About tiakis Biotech AG tiakis focuses on the discovery and development of therapeutic solutions based on its innovative biopharmaceutical Tiprelestat for life-threatening surgeries and life-threatening diseases such as PAH and COVID-19. tiakis seeks partners and investors for the development, commercial-scale manufacturing, marketing and distribution of the product. The company tiakis Biotech AG is located in Kiel, Germany ( ). About Northway Biotech Northway Biotech is a leading contract development and manufacturing organization (CDMO) supporting customers worldwide. Its highly experienced, professional team executes projects at any stage, from cell line construction and process development to cGMP manufacturing of biopharmaceutical products. The company's wide-ranging expertise and vertically integrated service offering translate to the ability to rapidly execute multiple projects from its state-of-the-art GMP facilities while ensuring full process and product compliance at all stages of research, development and commercial manufacturing. Northway Biotech is a privately owned company founded in 2004 and located in Vilnius, Lithuania, London, United Kingdom, and in Waltham, MA, US. Further information can be found on Northway's website . Contact Information Vladas Bumelis CEO and Chairman of the Board vladas.bumelis@northwaybiotech.com SOURCE: Northway Biotech View source version on accesswire.com:

100 项与 Tiprelestat(Proteo Biotech AG) 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	Tiprelestat(Proteo Biotech AG)	-	DB05161

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适应症	最高研发状态	国家/地区	公司	日期
心肌再灌注损伤	临床2期	英国	tiakis BIOTECH AG	2011-07-28
术后炎症	临床2期	德国	tiakis BIOTECH AG	2008-10-27
肺动脉高压	临床1期	美国	Stanford University	2019-03-18
肺移植排斥反应	临床前	美国	Stanford University	-

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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


DRKS00031463 (COMCOVID, PipelineReview) 人工标引	临床1/2期	新型冠状病毒感染	17	Tiprelestat	簾艱積衊憲選構廠構積(製夢壓餘鬱網衊膚齋鹹) = 鑰膚顧簾廠憲顧齋齋簾窪餘鏇廠觸糧願艱願艱 (鹹選壓淵夢網餘網窪廠, 3.6) 更多	积极	2024-12-09
				Placebo	簾艱積衊憲選構廠構積(製夢壓餘鬱網衊膚齋鹹) = 齋範簾醖選糧鹹衊簾簾窪餘鏇廠觸糧願艱願艱 (鹹選壓淵夢網餘網窪廠, 6.2) 更多
WCD2023	N/A	急性移植物抗宿主病 elafin	-	elafin (GVHD)	觸顧鹹積獵繭齋網廠積(鑰遞窪襯網醖顧糧艱蓋) = 製糧網顧糧顧築鑰觸艱衊衊鹹襯襯範淵襯構醖 (獵構襯蓋餘衊鏇鹹夢夢 )	-	2023-07-03
				elafin (non-GVHD rash)	簾廠願膚遞壓選餘醖簾(構壓簾鏇簾鑰構鑰醖艱) = 繭壓齋膚鏇網鹽構淵膚淵築範襯築願構鬱築網 (顧淵壓鑰鏇窪糧壓顧鏇 )