Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.

开始日期2020-04-30

申办/合作机构

APEIRON Biologics AG

EUCTR2020-001172-15-AT

/ Not yet recruiting临床2期

Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19 - APN01-01-COVID19

开始日期2020-04-10

申办/合作机构

APEIRON Biologics AG

NCT04287686

/ WithdrawnN/AIIT

A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19

This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted.

开始日期2020-02-01

申办/合作机构

广州医科大学附属第一医院（广州呼吸中心）

100 项与 GSK-2586881 相关的临床结果

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100 项与 GSK-2586881 相关的转化医学

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100 项与 GSK-2586881 相关的专利（医药）

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项与 GSK-2586881 相关的文献（医药）

2024-04-01·International journal of pharmaceutics

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

Article

作者: Ong, Hui Xin ; Baldelli, Alberto ; Singh, Anika ; Traini, Daniela ; Gholizadeh, Hanieh ; Jerry Wong, Chun Yuen ; Guo, Yigong ; Pratap-Singh, Anubhav ; Oguzlu, Hale

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

2024-01-01·ERJ open research

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2

Article

作者: Bergmann, Felix ; Al-Jalali, Valentin ; Bauer, Martin ; Steindl, Ariane ; Zeitlinger, Markus ; Wölfl-Duchek, Michael ; Wimmer, Doris ; Idzko, Marco ; Jorda, Anselm ; Bischof, Sarah ; Gugenberger, Romana ; Nussbaumer-Pröll, Alina

Background:

APN01 is a soluble recombinant human angiotensin-converting enzyme 2 (rhACE2), a key player in the renin–aldosterone–angiotensin system (RAAS). In clinical studies, APN01 was administered intravenously only, so far. The aim of this study (ClinicalTrials.gov:NCT05065645) was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled APN01.

Methods:

This was a phase I, double-blind, placebo-controlled, dose-escalation study. Inhalation was conductedviaa nebuliser over 15 min in three single ascending dose (SAD) cohorts (n=24) and two multiple ascending dose (MAD) cohorts (n=16: every 12 h for 7 days). Doses in the SAD cohort were 1.25, 2.5 and 5 mg·mL−1; doses in the MAD cohort were 2.5 and 5 mg·mL−1. Safety (including adverse events (AEs), laboratory findings and lung function results), PK and PD data were assessed.

Results:

In the SAD and MAD cohorts, treatment-related AEs were slightly more frequent in the active treatment group than in the placebo group. AEs were mild to moderate, with no dose-limiting toxicities. No clinically relevant changes in lung function and laboratory results were observed. The mean maximum observed plasma concentration (Cmax) values after single and multiple doses of 5 mg·mL−1APN01 were 1.88 and 6.61 ng·mL−1, respectively. Among the PD variables, significance was found for ACE2 and angiotensin 1–5.

Conclusions:

The application of aerosolised APN01 is safe and well tolerated after single and multiple doses. By achieving a high local concentration in the lungs and low systemic bioavailability, inhaled rhACE2 may present a therapeutic option in ACE2-related diseases.

2023-11-01·Journal of medical virology

Molecular PET/CT mapping of rhACE2 distribution and quantification in organs to aid in SARS‐CoV‐2 targeted therapy

Article

作者: Dong, Bin ; Wang, Zilei ; Liu, Qi ; Li, Chuangui ; Liu, Youping ; He, Chengxue ; Liu, Song ; Zhao, Chuanke ; Liu, Jiayue ; Ding, Jin ; Zhu, Hua ; Yang, Zhi

Abstract:

Coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, poses a significant threat to public health. Angiotensin‐converting enzyme 2 (ACE2) is a key receptor for SARS‐CoV‐2 infection. Recombinant human ACE2 (RhACE2), as a soluble supplement for human ACE2, can competitively block SARS‐CoV‐2 infection. In this study, a mouse organ in situ rhACE2 high aggregation model was constructed for the first time, and in vivo real‐time positron emission tomography (PET) imaging of rhACE2 in the mouse model was performed using an ACE2‐specific agent 68Ga‐HZ20. This radiotracer exhibits reliable radiochemical properties in vitro and maintains a high affinity for rhACE2 in vivo. In terms of probe uptake, 68Ga‐HZ20 showed a good target‐to‐nontarget ratio and was rapidly cleared from the circulatory system and excreted by the kidneys and urinary system. PET imaging with this radiotracer can noninvasively and accurately monitor the content and distribution of rhACE2 in the body, which clarifies that rhACE2 can aggregate in multiple organs, suggesting the preventive and therapeutic potential of rhACE2 for SARS‐CoV‐2 and COVID‐19.

项与 GSK-2586881 相关的新闻（医药）

2023-03-30

·PRNewswire

Extremely Robust Acute Respiratory Distress Syndrome Pipeline Featuring 100+ Companies Expected to Change the Pace of the ARDS Treatment | DelveInsight

The rise in the incidence of ARDS stimulates the research and development of the drug, as it is likely to provide an appropriate environment for newer products to be profitable. Companies across the globe have shifted their focus toward the treatment of ARDS. The increase in the incidence will potentiate the treatment market for ARDS. Treatment goals, such as "permissive atelectasis", "permissive hypercapnia", and even "permissive hypoxemia", have been introduced as targets of ventilatory support. Together with the increased knowledge and understanding of how mechanical ventilation can harm the lungs, a major effort has been put into preventing or shortening the use of mechanical ventilation as much as possible and using settings that are considered to be "lung-protective." Several other supportive care options are available, but they all do not withstand the current needs of patients for this indication. LAS VEGAS, March 30, 2023 /PRNewswire/ -- DelveInsight's ' Acute Respiratory Distress Syndrome Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline acute respiratory distress syndrome therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the acute respiratory distress syndrome pipeline domain. Key Takeaways from the Acute Respiratory Distress Syndrome Pipeline Report DelveInsight's acute respiratory distress syndrome pipeline report depicts a robust space with 100+ active players working to develop 105+ pipeline therapies for acute respiratory distress syndrome treatment. Key acute respiratory distress syndrome companies such as Biocon, NRx Pharmaceuticals, Humanigen, Mesoblast, Sage Therapeutics, Evgen Pharma, Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Healthcare, Foresee Pharmaceuticals, BioMarck Pharmaceuticals, Boehringer Ingelheim, Biohaven Pharmaceuticals, Biophytis, NovImmune SA, Constant Therapeutics, Windtree Therapeutics, Acticor Biotech, Direct Biologics, F4 Pharma, Apeiron Biologics, Trevena, Synact Pharma, Pluristem Therapeutics, UCB Pharma, Chiesi Farmaceutici, and others are evaluating new acute respiratory distress syndrome drugs to improve the treatment landscape. Promising acute respiratory distress syndrome pipeline therapies in various stages of development include Itolizumab, ZYESAMI, Lenzilumab, Remestemcel-L, Brexanolone, SFX-01, DMX-200, Tradipitant, Siltuximab, VERU 111, BIO 11006, FP025, Alteplase, Sarconeos Zavegepant, EB 05, USB 002, Sinapultide, Glenzocimab, DB 001, FX06, APN01, TRV 027, AP1189, PLX PAD, Zilucoplan, CHF5633, and others. In March 2023, Tetra Bio-Pharma received up to $150,000 in funding from the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP) to support a research and development project to enable the development of its ARDS-003 oral formulation. Specifically, the funds will be used to optimize the formulation and perform animal non-GLP Pharmacokinetic Studies. In February 2021, Avid Bioservices and Humanigen announced that they had entered into a manufacturing services agreement to expand production capacity for lenzilumab. Under the terms of this Current Good Manufacturing Practice (cGMP) agreement, Avid would initiate technical transfer and analytical validation activities for lenzilumab with the goal of delivering cGMP drug substance batches to support Humanigen's regulatory and potential commercial activities. Request a sample and discover the recent advances in ARDS drug treatment @ Acute Respiratory Distress Syndrome Pipeline Report The acute respiratory distress syndrome pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage acute respiratory distress syndrome drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the acute respiratory distress syndrome clinical trial landscape. Acute Respiratory Distress Syndrome Overview Acute respiratory distress syndrome (ARDS) is a rapidly progressing condition that primarily affects the critically ill. The most serious complication of ARDS is fluid leaking into the lungs, making breathing difficult or impossible. The ARDS causes are classified as direct or indirect lung injuries. Direct lung injuries include pneumonia, aspiration, trauma, and others. Examples of indirect lung injuries include pancreatic inflammation, severe infection (also known as sepsis), blood transfusions, burns, and pharmaceutical responses. ARDS symptoms include shortness of breath, coughing, and fever; in some cases, high heart rates and rapid breathing have also been observed. Patients with ARDS may experience chest pain, especially during inhalation, and some may develop blue nails and lips due to drastically reduced oxygen levels in the blood. Mechanical ventilation, stress ulcer and venous thromboembolism prevention, nutritional support, and underlying damage therapy are all part of the acute respiratory distress syndrome treatment. Find out more about drugs for ARDS @ New Acute Respiratory Distress Syndrome Drugs A snapshot of the Acute Respiratory Distress Syndrome Pipeline Drugs mentioned in the report: Learn more about the emerging acute respiratory distress syndrome pipeline therapies @ ARDS Clinical Trials Acute Respiratory Distress Syndrome Therapeutics Assessment The acute respiratory distress syndrome pipeline report proffers an integral view of acute respiratory distress syndrome emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Acute Respiratory Distress Syndrome Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor antagonists, Hedgehog protein modulators, Histone deacetylase inhibitors, NF E2 related factor 2 stimulants, Wnt signalling pathway modulators, Cell replacements, Toll-like receptor 4 antagonists, Fibrinolytic agents, Plasminogen activator stimulants, Plasminogen activators, Myristoylated alanine-rich C kinase substrate inhibitors, Cell membrane permeability enhancers, Sodium channel agonists Key Acute Respiratory Distress Syndrome Companies: Biocon, NRx Pharmaceuticals, Humanigen, Mesoblast, Sage Therapeutics, Evgen Pharma, Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Healthcare, Foresee Pharmaceuticals, BioMarck Pharmaceuticals, Boehringer Ingelheim, Biohaven Pharmaceuticals, Biophytis, NovImmune SA, Constant Therapeutics, Windtree Therapeutics, Acticor Biotech, Direct Biologics, F4 Pharma, Apeiron Biologics, Trevena, Synact Pharma, Pluristem Therapeutics, UCB Pharma, Chiesi Farmaceutici, and others. Key Acute Respiratory Distress Syndrome Pipeline Therapies: Itolizumab, ZYESAMI, Lenzilumab, Remestemcel-L, Brexanolone, SFX-01, DMX-200, Tradipitant, Siltuximab, VERU 111, BIO 11006, FP025, Alteplase, Sarconeos Zavegepant, EB 05, USB 002, Sinapultide, Glenzocimab, DB 001, FX06, APN01, TRV 027, AP1189, PLX PAD, Zilucoplan, CHF5633, and others. Dive deep into rich insights for new drugs for ARDS treatment; visit @ Acute Respiratory Distress Syndrome Medications Table of Contents For further information on the acute respiratory distress syndrome pipeline therapeutics, reach out @ Acute Respiratory Distress Syndrome Drug Treatment Related Reports Acute Respiratory Distress Syndrome Market Acute Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key acute respiratory distress syndrome companies, including Cellular Biomedicine Group, Baylx, Histocell, Cartesian Therapeutics, Cynata Therapeutics, Immunovative Therapies, Orbsen Therapeutics, Celularity, Bonus BioGroup, Diffusion Pharmaceuticals, among others. Respiratory Distress Syndrome Market Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key respiratory distress syndrome companies, including Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Inc., BioMarck Pharmaceuticals, CTI BioPharma, Athersys, Foresee Pharmaceuticals, Boehringer Ingelheim, among others. Chronic Obstructive Pulmonary Disease Market Chronic Obstructive Pulmonary Disease Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key chronic obstructive pulmonary disease companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma, among others. Asthma Pipeline Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including GSK, AstraZeneca, Teva Pharmaceuticals, among others. Severe Asthma Pipeline Severe Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key severe asthma companies, including AstraZeneca, Novartis, Sanofi, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Additionally, get in touch with our business executive to explore @ Healthcare Due Diligence Services Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

2022-12-12

·生物制药小编

七大类经典抗病毒药物

SARS-CoV-2病毒的大流行刺激了已知抗病毒药物的发展和新型抗病毒药物的发现。根据疾控中心和世卫组织的说法，防护服、口罩、洗手、用洗涤剂清洁表面、社交距离、旅行限制和隔离感染者都有助于限制呼吸道病毒的传播。疫苗接种大大保护了人群对SARS-CoV-2感染。抗病毒药物也对病毒感染提供了预防和治疗保护。目前大约100种单一和联合抗病毒药物已经获得批准，而数千种正在积极开发中。抗病毒药物可以根据靶点进行划分，靶点可以是宿主或病毒成分。病毒靶向的药物结合病毒蛋白质或核酸，参与病毒进入、转录、复制、组装和释放。宿主靶向的抗病毒药物调节参与病毒合成、加工和运输的宿主因子和信号通路的活性。抗病毒药物有多种分子形式，包括小分子、多肽、中和抗体、干扰素、CRISPR-CAS系统、si/shRNA和其他核酸聚合物(NAP)（图1）。本文就七大类经典的抗病毒药物做一个简要介绍。图1. 抗病毒药物以及它们潜在的来源和影响病毒复制的阶段病毒中和抗体病毒中和抗体(nAbs)附着在病毒表面蛋白上，阻止病毒进入宿主的细胞。nAbs还会向免疫细胞发出信号，让它们来帮助摧毁病毒。Nabs的产生有不同的来源：来源于人的nAbs血浆可以从接种疫苗的或最近从相关病毒疾病中恢复的患者那里收集。只有一些血浆样本含有高滴度的nAbs。血浆可用于将被动抗体免疫转移给最近感染或尚未接触病毒的人。然而，恢复期血浆治疗病毒感染的益处尚不确定。也可以从最近康复或接种疫苗的人身上采集外周血单个核细胞(PBMC)。在鉴定出对病毒抗原的血清学反应后，可以克隆B细胞的抗体基因，然后生产、纯化和鉴定具有预防或治疗的益处的nAbs。然而，在某些情况下，抗体不足以产生免疫反应，则可能导致抗体依赖增强(ADE)作用，此类抗体会促进病毒进入和感染宿主细胞，导致传染性和毒力增强。来源于哺乳动物的人源性nAbs当很难从受感染或接种疫苗的人身上获得血液样本时，实验室哺乳动物可以在适当的安全条件下用作生产nAbs的来源。例如，小鼠可以分别用病毒或其成分免疫。然后进行结合分析或基于ELISA的受体阻断分析来筛选和选择nAbs克隆。然后将抗体人源化，由此产生的人源化的nAbs可以用作人类的治疗剂。从初乳中提取nAbs怀孕的大型哺乳动物在免疫后产生抗体，并在后代出生前立即进入初乳。这些从初乳中提取的多克隆nAbs在体内已经显示了作为预防流感和SARS-CoV-2感染的潜在药物的潜力。重组人受体作为抗病毒药物虽然病毒可能发生突变并逃逸抗体的识别，但它们必须保持与宿主受体(hRs)结合的能力。研究表明，重组人血管紧张素转换酶2(rhACE2)受体可阻断SARS-CoV-2感染。此外，rhACE2能抵抗病毒逃逸。因此，基于重组可溶性hRs的中和生物制品是抗病毒药物开发的一个潜在策略。基于CRISPR/Cas抗病毒治疗CRISPR/Cas系统是一种适应性免疫系统，可防止噬菌体和外来核酸入侵。基于Cas9-、Cas12-(切割dsDNA)和Cas13-(切割ssRNA)的系统已被用于治疗哺乳动物体内和体外的病毒感染。例如，EBT-101是人类首次使用腺相关病毒递送CRISPR/Cas9系统来对抗艾滋病毒。CRISPR/Cas9系统也可以靶向dsDNA病毒基因组并破坏其复制。使用CRISPR/Cas13可以检测和抑制IAV、LSMV、VSV、SARS-CoV2和其他单链RNA病毒感染。抗病毒干扰素干扰素(IFN)是一组信号蛋白，由人类细胞在感染多种病毒时产生和释放，导致感染细胞中病毒核酸的降解，并在附近的未感染细胞中触发抗病毒反应。干扰素根据它们所结合的细胞受体进行分类。I型IFN(IFN-α、IFN-β、IFN-ε、IFN-kappa和IFN-omega)与IFNAR1/2结合，II型IFN(IFN -γ)与IFNGR1/2结合，而III型IFN(IFN-lambda-1-4)与IL-10受体2共同激活IFNL受体。重组人干扰素已被批准用于治疗丙型肝炎病毒和乙肝病毒感染。尽管重组人干扰素对包括冠状病毒在内的多种其他病毒有效，但它们的疗效有限，并可能在体内引起不良反应。抗病毒多肽抗病毒多肽(AVP)已被证实能干扰病毒复制。根据其作用机制可分为结合/附着抑制剂、融合和进入抑制剂、病毒酶抑制剂、病毒组装抑制剂和对病毒有间接作用的多肽等。AVP可以根据现有的病毒蛋白结构信息进行计算设计和化学合成，也可以天然获得。一些 AVP序列及其MOA可在http://crdd.osdd.net/servers/avpdb/服务器中找到，其包含经过实验验证的近三千个AVP。AVP还可以作为其他抗病毒药物的递送载体。抗病毒核酸聚合物抗病毒核酸聚合物(NAP)可以通过与病毒颗粒或RNA/DNA复制中间体结合，直接抑制病毒进入或复制。几种NAP正在开发中，用于治疗丙型肝炎、流感病毒、单纯疱疹病毒和艾滋病毒感染。特别是，si/shRNAs可以通过RNA干扰在哺乳动物细胞中引导特定的病毒清除。NAP可以根据病毒的现有结构信息进行计算设计，也可以通过化学方法进行设计合成，或者在原位或体外生产。NAP也可以作为其他分子形式的抗病毒药物的递送载体。小分子抗病毒药物小分子抗病毒药物可减弱病毒复制。一些小分子为天然来源，而另一些则是化学合成的。一些小分子影响病毒因子的关键功能，而其他小分子则干扰宿主因子和病毒复制所需的途径。此外，一些小分子调节抗病毒和炎症反应的发展。宿主靶向的小分子中一个有趣的亚类是促凋亡剂，它可以促进感染细胞的死亡，而不影响未受感染的细胞。与病毒靶向的抗病毒药物相比，宿主靶向的小分子往往有更多的副作用。广谱抗病毒药物抗病毒药物可以针对一种或多种病毒。抑制多种病毒复制的药物被称为广谱抗病毒药物(BSA)。抑制来自相同或不同病毒家族的病毒复制的BSA分别称为家族内或家族间抗病毒药物(图2)。例如，IFN-α、IFN-β、ribavirin、瑞德西韦和法匹拉韦是家族间药物，而minocycline (抑制黄病毒科)和brivudine (抑制疱疹病毒科)是家族内BSA。DrugVirus.Info服务器汇总了两百多个BSA。图2. 广谱抗病毒药物(BSA)抗病毒药物的组合为了靶向多个病毒并减轻抗病毒耐药性的发展，可以同时给予几种抗病毒药物。具有协同作用的抗病毒鸡尾酒疗法含有较低浓度的药物，其可能会减少大剂量单一疗法相关的副作用。AntiviralCombi.Info服务器汇总了可用的抗病毒药物组合的信息，DrugVirus.Info服务器显示了含有BSA的药物组合(图3)。图3. BSA与分组不同家族的病毒之间的关系小编小结到目前为止，已经批准了大约100种单一和联合抗病毒疗法，而数千种正处于临床前期或临床开发中。本文简要介绍了七类经典的抗病毒药物。另外，干扰素和一些小分子单独或联合具有广谱的抗病毒活性，这可能有助于治疗新出现和再次出现的病毒感染。此外，我们必须开发新的方法，以应对快速进化的病毒。参考文献Seven classes of antiviral agents.A review: mechanism of action of antiviral drugs.

疫苗

2022-11-03

·GlobeNewswire-Health Care

APEIRON Respiratory Therapies announces positive results from Phase I trial of inhaled APN01

Administration of aerosolized APN01 shown to be safe and well tolerated at all dose levels, with no adverse events above Grade 2Investigators recommend further development of inhaled APN01, which may be an effective treatment for acute and chronic respiratory conditions including PAH, ARDS and COVID-19APN01 is available for out-licensing to maximize the program’s development and commercial potential VIENNA, Austria, Nov. 03, 2022 (GLOBE NEWSWIRE) -- APEIRON Respiratory Therapies GmbH (“AResT”), a privately held biotech company focusing on the discovery and development of treatments for respiratory diseases, today announces positive final results from a Phase I clinical trial of inhaled APN01 (alunacedase alfa), a soluble recombinant version of the SARS-CoV-2 cell entry receptor ACE2. The study met all primary and secondary endpoints, with all results indicating that the inhalation of APN01 at all dosage levels used in the trial is safe and well tolerated. In the study, no dose-limiting toxicities were observed. No serious adverse events were reported, and no patients withdrew from the trial. Professor Markus Zeitlinger, Head of the Department of Clinical Pharmacology at the Medical University of Vienna and Principal Investigator for the study, said: “I am very happy that our team was able to contribute to the development of this potential treatment for patients suffering from different forms of severe respiratory disease. The inhaled route of administration may enable the achievement of very high concentrations at the site of action, without compromising patient safety due to systemic side effects. We were able to confirm a good tolerability profile from a clinical perspective.” Dr Romana Gugenberger, Chief Medical and Scientific Officer of AResT, said: “The results of this study allow further clinical development of novel inhaled APN01 and expand its potential as a treatment for a range of respiratory diseases. In addition to meeting all primary endpoints regarding the safety and tolerability of APN01 via a new route of administration, the observed low systemic concentrations of ACE2 indicate that inhaled APN01 may be an effective treatment for chronic conditions such as pulmonary arterial hypertension as well as acute indications like COVID-19.” In a completed double-blind, placebo-controlled Phase 2 trial, intravenously administered APN01 showed potential clinical benefit against COVID-19. The drug candidate also may have potential in other respiratory diseases such as acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH). APN01 was previously developed by APEIRON Biologics AG, a privately held biotech company based in Vienna, Austria, and out-licensed to AResT, which was demerged from APEIRON Biologics AG in 1H 2022 to continue the development of APN01. AResT is a 100% subsidiary of invIOs GmbH (“invIOs”), which was also demerged from APEIRON Biologics AG in 1H 2022 to focus on the discovery and development of innovative cancer immunotherapies. Peter Llewellyn-Davies, CEO of invIOs, said: “We are pleased with the results of this study, as it opens numerous additional avenues for the further development of APN01. With the current trial of inhaled APN01 and our previous Phase 2 trial using intravenous administration in COVID-19, we have shown that APN01 is a safe and well tolerated potential treatment approach for a number of respiratory diseases. We are therefore actively reviewing out-licensing options to drive the further development of APN01, and welcome additional expressions of interest from potential partners.” Inhaled APN01 Phase 1 trial design The double-blind, placebo-controlled, dose-escalation study was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled APN01. The trial enrolled 40 healthy adult subjects aged 18-55 years. The primary objective of the trial was to evaluate the safety and tolerability of single ascending doses (SADs) and multiple ascending doses (MADs) of inhaled APN01 administered via a jet nebulizer. Secondary objectives included evaluation of the maximum tolerated dose and investigation of the potential immunogenicity of inhaled APN01. Inhaled APN01 Phase 1 trial final results Safety Treatment was safe and well tolerated. All adverse events were mild to moderate with none above Grade 2.No dose-dependent toxicities were observed. Maximum tolerated dose No dose-limiting toxicities were observed. Accordingly, the maximum tolerated dose as defined by the study was the highest dose level in the MAD cohort. Immunogenicity No anti-APN01 antibodies were detected in any of the subjects. A paper describing the trial and its full results is in preparation. About APN01 APN01 is a soluble recombinant human Angiotensin Converting Enzyme 2 (rhACE2). Several studies have shown that human ACE2 is a key enzyme regulator of the Renin Angiotensin Aldosterone System (RAAS), a hormone system involved in regulation of blood pressure, lung disorders, diabetic kidney disease, inflammation, or cardiovascular diseases. ACE2, a homologue of ACE, has vasodilative and biological effects on vascular remodeling exercised through hydrolysis of Ang‐II to Ang(1‐7). Ang(1‐7) counteracts Ang‐I effects and thereby reduces blood pressure, diminishes inflammation, and protects multiple organs such as the heart, kidney, liver, lung and vasculature from damage. In addition, APN01 mimics ACE2, a receptor identified as the critical cellular entry receptor for the SARS-CoV-2 virus and therefore plays a crucial role in combating COVID-19. In addition to blocking the access of SARS-CoV-2 to its cell membrane-bound entry gate, the enzyme function of APN01, engineered into the same drug, potentially leads to reduction of organ injuries in COVID-19. Due to the unique therapeutic approach of using the soluble form of the SARS-CoV-2 entry receptor ACE2, APN01 is inherently resilient to viral escape, and thus an optimal drug candidate for novel variants of concern, as already shown for many variants of concern in clinical studies. In a double-blind, randomized, placebo-controlled, interventional Phase 2 trial evaluating intravenously administered APN01 in patients with severe COVID-19, APN01 appeared to reduce the number of deaths and the number of patients requiring invasive ventilation and was shown to be well tolerated with a favorable safety profile. About AResT AResT was spun out of APEIRON Biologics AG at the beginning of 2022 to continue the development of APN01. AResT is a 100% subsidiary of invIOs GmbH, which focuses on the development of the immuno-oncology assets of APEIRON Biologics. More information on the demerger of AResT and invIOs from APEIRON Biologics AG can be found on the invIOs website here. About invIOs invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of innovative cancer immunotherapies. EPiC, invIOs’s proprietary cell therapy platform for intracellularly modifying gene expression, enables rapid treatment of patients in an out-patient setting using their own fresh immune cells. Once clinically validated, this novel concept will allow access to and treatment for indications not previously addressable by immunotherapy. The first EPiC-based candidate, APN401, is currently being evaluated in a clinical Phase 1b trial in patients with advanced solid tumors. Two further projects – a second EPiC-based candidate and a novel small molecule – are currently in pre-clinical development. For further information, please visit www.invios.com and connect with us on LinkedIn. Contacts AResTEmail: investors@ares-t.com invIOs Peter MorleyHead of CommunicationsT +43 1 8656577 121Email: investors@invios.com MC Services AGRaimund Gabriel, Laurie Doyle, Dr Regina LutzEurope: +49 89 210 228 0US: +1 339 832 0752Email: invios@mc-services.eu

抗体细胞疗法免疫疗法小分子药物并购

100 项与 GSK-2586881 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15736

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
新型冠状病毒感染	临床2期	奥地利	APEIRON Biologics AG	2020-04-30
新型冠状病毒感染	临床2期	丹麦	APEIRON Biologics AG	2020-04-30
新型冠状病毒感染	临床2期	德国	APEIRON Biologics AG	2020-04-30
新型冠状病毒感染	临床2期	俄罗斯	APEIRON Biologics AG	2020-04-30
新型冠状病毒感染	临床2期	英国	APEIRON Biologics AG	2020-04-30
肺动脉高压	临床2期	美国	GSK Plc	2018-02-21
肺动脉高压	临床2期	德国	GSK Plc	2018-02-21
肺动脉高压	临床2期	西班牙	GSK Plc	2018-02-21
急性肺损伤	临床2期	美国	GSK Plc	2012-09-01
急性肺损伤	临床2期	加拿大	GSK Plc	2012-09-01

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临床结果

适应症

分期

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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


NCT03000686 (Pubmed) 人工标引	临床1期	缺氧	17	GSK2586881	夢鏇願願簾窪鏇襯憲憲(獵獵獵觸夢簾齋鬱網艱) = There were no clinically relevant differences (defined as a reduction of ≥ 5 mmHg) in change from baseline in PASP between GSK2586881 and placebo. 齋醖醖繭蓋遞淵鹹觸齋 (鹽鹽艱齋簾鹹鏇顧醖鬱 ) 更多	不佳	2021-12-01
				Placebo
NCT04335136 (APN01-COVID-19, CTgov)	临床2期	新型冠状病毒感染	185	RhACE2 APN01 (Group A (Active) APN01)	繭壓醖鹽網壓醖選構齋(窪蓋鬱顧鬱醖淵獵顧構) = 鹽鏇壓糧範艱選鹽窪糧衊獵淵膚積鹽膚夢醖廠 (繭積醖齋觸遞鑰鏇壓鹽, 製廠網觸鑰範鬱膚觸膚 ~ 鹹淵糧獵鹹壓簾繭製遞) 更多	-	2021-08-02
				Physiological saline solution (Group B (Placebo Control))	繭壓醖鹽網壓醖選構齋(窪蓋鬱顧鬱醖淵獵顧構) = 鹹鹽獵獵範餘繭齋構選衊獵淵膚積鹽膚夢醖廠 (繭積醖齋觸遞鑰鏇壓鹽, 襯繭鹹窪願願廠構網淵 ~ 製艱廠淵繭選獵窪襯築) 更多
NCT03177603 (CTgov)	临床2期	肺动脉高压	23	GSK2586881 (GSK2586881 0.1 mg/kg)	夢選網簾築廠製構夢選(顧餘憲艱鬱廠選遞鹽廠) = 網鏇簾網繭繭鹹鹽構窪願鑰淵糧夢網範憲構築 (鏇構製餘艱憲構繭選餘, 網觸築醖醖製襯鑰壓膚 ~ 鏇夢繭構構鏇願衊餘選) 更多	-	2020-04-21
				GSK2586881 (GSK2586881 0.2 mg/kg)	夢選網簾築廠製構夢選(顧餘憲艱鬱廠選遞鹽廠) = 廠鬱獵範遞餘襯廠糧簾願鑰淵糧夢網範憲構築 (鏇構製餘艱憲構繭選餘, 選鏇顧壓遞獵醖憲簾觸 ~ 廠鏇艱構膚齋鹹憲齋夢) 更多
NCT03000686 (CTgov)	临床1期	缺氧	17	placebo (Part 1: Placebo)	廠觸醖夢網壓願艱築衊(鑰壓鑰鹹獵築選蓋艱夢) = 積衊齋製廠鹽廠鹽選糧遞憲淵鹹顧壓獵製餘鬱 (鏇襯膚遞膚範衊繭繭衊, 窪鹽壓淵醖構糧獵遞糧 ~ 築醖網積衊廠鹹醖範衊) 更多	-	2019-12-23
				GSK2586881 (Part 1: GSK2586881 0.8 mg/kg)	廠觸醖夢網壓願艱築衊(鑰壓鑰鹹獵築選蓋艱夢) = 艱壓壓齋繭築鹽遞齋廠遞憲淵鹹顧壓獵製餘鬱 (鏇襯膚遞膚範衊繭繭衊, 鹽鬱廠鹽憲築壓網製膚 ~ 構艱範糧鹽淵製簾壓衊) 更多
NCT01597635 (CTgov)	临床2期	急性肺损伤	44	Dose 4 GSK2586881	顧窪夢艱顧製壓遞膚衊(鹽醖壓製壓選蓋顧繭壓) = 艱製構餘願鹽襯艱蓋鏇製積憲遞築顧餘獵繭製 (鹹衊築艱餘繭鹽糧簾積, 鏇顧壓憲醖艱齋鏇廠顧 ~ 窪夢夢醖簾繭艱顧鏇廠) 更多	-	2017-09-28