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

Start Date30 Apr 2020

Sponsor / Collaborator

APEIRON Biologics AG

EUCTR2020-001172-15-DE / Not yet recruitingPhase 2

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

Start Date08 Apr 2020

Sponsor / Collaborator

APEIRON Biologics AG

NCT04287686 / WithdrawnNot ApplicableIIT

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.

Start Date01 Feb 2020

Sponsor / Collaborator

The First Affiliated Hospital of Guangzhou Medical University

100 Clinical Results associated with GSK-2586881

100 Translational Medicine associated with GSK-2586881

100 Patents (Medical) associated with GSK-2586881

Literatures (Medical) associated with GSK-2586881

01 Nov 2023·Journal of medical virology

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

Article

Author: Liu, Qi ; Dong, Bin ; Wang, Zilei ; 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.

01 Jan 2023·Annals of translational medicine

Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

Article

Author: Hu, Zhenjie ; Chen, Yuhong ; Zhou, Pan ; Wu, Chunxue

Background:

Sepsis-induced cardiac dysfunction (SICD) is a common complication of sepsis and contributes to mortality and the complexity of management in patients with sepsis. Recombinant human angiotensin-converting enzyme 2 (rhACE2) has been reported to protect the heart from injury and dysfunction in conditions which involve increased angiotensin II (Ang II). In this study, we aimed to detect the effects of rhACE2 on SICD.

Methods:

A SICD model was developed in male C57/B6 mice by lipopolysaccharide (LPS) intraperitoneal injection. When cardiac dysfunction was confirmed by echocardiography 3 hours after LPS administration, mice were treated with either saline, rhACE2, or rhACE2 + A779. All mice received echocardiographic examination at 6 hours after LPS injection and then were sacrificed for serum and myocardial tissues collection. Angiotensin, cardiac troponin I (cTnI), and inflammatory markers in serum were measured. Histopathology features were examined by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining to evaluate structure injury and cell pyroptosis rate in heart tissue respectively. Pyroptosis-related proteins and signaling pathways involved in nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in heart tissue were investigated by western blot (WB).

Results:

RhACE2 relieved myocardial injury and improved cardiac function in mice with SICD accompanied by decrease of Ang II and increase of angiotensin 1-7 (Ang 1-7) in serum. RhACE2 diminished activation of NLRP3 inflammasome, inflammatory response, and cell pyroptosis induced by LPS. In addition, rhACE2 partly inhibited activation of nuclear factor κB (NF-κB), the p38 mitogen-activated protein kinase (MAPK) pathway, and promoted activation of the AMP-activated protein kinase-α1 (AMPK-α1) pathway in heart tissue. Administration of A779 offset the inhibitive effects of rhACE2 on NLRP3 expression and protective role on cardiac injury and dysfunction in mice with SICD.

Conclusions:

RhACE2 plays a protective role in SICD, ameliorating cardiac injury and dysfunction through NF-κB, p38 MAPK, and the AMPK-α1/NLRP3 inflammasome pathway dependent on converting Ang II to Ang 1-7.

01 Jul 2022·Protein and peptide letters

Utilization of SUMO Tag and Freeze-thawing Method for a High-level Expression and Solubilization of Recombinant Human Angiotensinconverting Enzyme 2 (rhACE2) Protein in E. coli

Article

Author: Farnoosh, Gholamreza ; Taheri, Ramezan Ali ; Bemani, Peyman ; Amini, Razieh ; Mohammadi, Mozafar ; Hashemzadeh, Mohammad Sadegh

Background::

SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor for entering the host cells. Production of the ACE2 molecule is important because of its potency to use as a blocker and therapeutic agent against SARS-CoV-2 for the prophylaxis and treatment of COVID-19.

Objective::

The recombinant human ACE2 (rhACE2) is prone to form an inclusion body when expressed in the bacterial cells.

Method::

We used the SUMO tag fused to the rhACE2 molecule to increase the expression level and solubility of the fusion protein. Afterward, the freeze-thawing method plus 2 M urea solubilized aggregated proteins. Subsequently, the affinity of solubilized rhACE2 to the receptor binding domain (RBD) of the SARS-CoV-2 spike was assayed by ELISA and SPR methods.

Results::

SUMO protein succeeded in increasing the expression level but not solubilization of the fusion protein. The freeze-thawing method could solubilize and recover the aggregated fusion proteins significantly. Also, ELISA and SPR assays confirmed the interaction between solubilized rhACE2 and RBD with high affinity.

Conclusion::

The SUMO tag and freeze-thawing method would be utilized for high-level expression and solubilization of recombinant rhACE2 protein.

News (Medical) associated with GSK-2586881

30 Mar 2023

·www.prnewswire.com

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. Other Trending Reports Tay-sachs Disease Or Gm2 Gangliosidosis Market | Onycholysis Market | Diagnostic Imaging Equipment Market | Chemotherapy-induced Peripheral Neuropathy Market | Global Electrophysiology Devices Market | Anaphylaxis Market | Atherectomy Devices Market | Helicobacter Pylori Infections Market | Ophthalmic Imaging Equipment Market | Androgenetic Alopecia Market | Allergic Rhinitis Market | Chronic Inflammatory Demyelinating Polyneuropathy Market | Chronic Inflammtory Demyelinating Polyneuropathy Market | Colorectal Cancer Crc Market | Opioid Induced Constipation Market | Vertigo Market | Bone Anchored Hearing Systems Market | Wound Closure Devices Market | Hip Replacement Devices Market | Hemodynamic Monitoring Systems Market | Egfr Non-small Cell Lung Cancer Market | Helicobacter Pylori Infection Market | Hyperkalemia Market | Polycythemia Market Neurostimulation Devices Market | Carpal Tunnel Syndrome Market | Ventilator Market | Cerebral Aneurysm Market | Alpha Antitrypsin Market | Binge Eating Disorder Market | Bunion Market | Concussions Market Size | Exocrine Pancreatic Insufficiency Market | Healthcare Due Diligence Services | Minimal Residual Disease Market | Hypertrophic Scar Market | Lung Fibrosis Market | Anterior Uveitis Market | 22q11.2 deletion syndrome Market | X-Linked Retinitis Pigmentosa (XLRP) Market | Acute Radiation Syndrome Market | Alpha-1 Protease Inhibitor Deficiency Market | Androgenetic Alopecia Market | Hyperlipidemia Market | Cardiotoxicity Market | Hypertrophic Cardiomyopathy Market | Fatty Acid Oxidation Disorders (FAODs) Market | Androgen Insensitivity Syndrome Market | Emphysema Market | Canaloplasty Market | Dravet Syndrome Market | Celiac Disease Market | Chlamydia Infections Market | Syphilis Market | Renal Tubular Acidosis Market | Palmoplantar Pustulosis (PPP) Market | Aplastic Anemia Market | Bacterial Pneumonia Market | B cell Chronic Lymphocytic Leukemia Market | B cell Lymphomas Market | Behcets Disease Market Neoantigen-based Personalized Cancer therapeutic Vaccines Competitive Landscape and Market Forecast—by 2035 | Glioblastoma Market Related Healthcare Blogs Promising Therapies in the ARDS Market Rising Acute Respiratory Distress Syndrome Prevalence ARDS Market Outlook Related Healthcare Services Healthcare Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. 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

03 Nov 2022

·www.globenewswire.com

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

AntibodyCell TherapyImmunotherapySmall molecular drugAcquisition

13 Oct 2021

·www.biospace.com

APEIRON Biologics commences clinical COVID-19 trial with inhaled APN01

• Inhalation of APN01 to directly target SARS-CoV-2 virus in respiratory tract, the lung and tissue itself • Primary objective is to evaluate safety and tolerability of inhaled APN01 • Phase 1 trial to enroll about 40 healthy volunteers • Additional US Phase 2 trial with intravenous administration of APN01 Vienna, Austria, 12 October 2021: APEIRON Biologics AG, a privately held biotechnology company developing novel immunotherapies for cancer and respiratory diseases, today announced the start of a company sponsored Phase 1 trial for inhalation of APN01. The double-blind, placebo-controlled, dose-escalation study plans to enroll about 40 healthy volunteers in Austria to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled APN01. Nebulized APN01 is a recombinant human angiotensin-converting enzyme 2 developed to treat COVID-19 patients by neutralizing SARS-CoV-2 in the lungs and mitigating lung damage caused by the infection. Primary study objective is the evaluation of safety and tolerability of single ascending doses (SADs) and multiple ascending doses (MADs) of inhaled APN01 when administered via a jet nebulizer in healthy subjects. Secondary objectives include the maximum tolerated dose and the effect of APN01 on key pharmacodynamic biomarkers of the renin-aldosterone-angiotensin system (RAAS). Romana Gugenberger PhD, CMSO of APEIRON Biologics AG, explains: “The start of this company sponsored trial for APN01 is a vital next step in our development approach. Delivering a therapy via inhalation rather than intravenously allows patients in earlier stages of the disease to treat themselves, optimize treatment costs and reduce risk contacts for healthcare professionals. This study will form the basis not only for the treatment of COVID-19 with inhaled APN01 but enables further development strategies in chronic respiratory diseases with high unmet medical need such as Chronic Obstructive Pulmonary Disease (COPD) and Pulmonary Arterial Hypertension (PAH).” Peter Llewellyn-Davies, CEO of APEIRON Biologics AG, adds: “We desperately need an effective treatment for COVID-19 and an inhaled application is an important strategic milestone for APEIRON. With the data from our concluded Phase 2 trial with APN01, recently supported by highly encouraging efficacy results in preclinical models, we are confident that inhalation with APN01 can deliver substantial benefits for patients suffering from COVID-19 infections. This is the third clinical trial dedicated to the multiarmed initiative of developing APN01 into vital therapy options in COVID-19. We look forward to the results of the ongoing trials which could pave the way for the future treatment of COVID-19 with APN01.” Univ. Prof. Dr. Markus Zeitlinger, Department of Clinical Pharmacology at the Medical University of Vienna and principal investigator of the trial, comments: “The trial aims to evaluate the drug delivery of APN01 through inhalation. Preliminary data from ongoing studies with inhalation of ACE2 based therapeutics show high efficacy in SARS-CoV-2 preclinical models. Delivery of the drug candidate directly to the respiratory tract should block viral entry into the lung cells and control inflammation. Importantly, APN01 may also be suitable against infections with variants of SARS-CoV-2 as already shown preclinically.” APEIRON’s previously completed Phase 2 trial with intravenously administered APN01 demonstrated significant improvement in certain parameters of the Renin Angiotensin Aldosterone System (RAAS) with APN01 treatment compared to placebo. Data also suggested that APN01 will confer greatest therapeutic benefit to patients with lower WHO-CPS (World Health Organization Clinical Progression Scale) scores. In parallel, APN01 is to be administered intravenously in a US Phase 2 trial conducted by the Vanderbilt University Medical Center (VUMC), Nashville, USA, and supported and funded by the National Institutes of Health (NIH). The four-arm, randomized, doubleblinded, placebo-controlled trial is enrolling approximately 1,600 COVID-19 patients at more than 50 sites in the United States. About APN01 (alunacedase alfa) APN01 is a soluble recombinant human Angiotensin Converting Enzyme 2 (rhACE2) which mimics ACE2, a receptor identified as the critical cellular entry receptor for the SARS-CoV2 virus and therefore plays a crucial role in combating COVID-19. The virus’ spike uses the ACE2 protein on the cell membrane to enter the cells. APN01 as a soluble form of ACE2, potentially prevents binding of the virus spike protein to the cell surface receptor and thereby preventing infection of cells. In addition, as shown in several studies human ACE2 is a key enzyme regulator of the Renin Angiotensin Aldosterone System (RAAS), a peptide system involved in blood pressure, lung disorders, diabetic kidney disease, inflammation, or cardiovascular diseases. ACE2 dials down the RAAS and thereby reduces blood pressure, diminishes inflammation, and protects multiple organs such as the heart, kidney, liver, lung or vasculature from damage. Thus, 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. Additionally, 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, thus an optimal drug candidate for novel variants of concern, as already shown for all variants of concern. APN01 was first discovered and developed in 2003 in response to the first SARS outbreak by the founder of APEIRON Biologics, Prof. Josef Penninger MD. About APEIRON Biologics AG APEIRON Biologics is a privately held biotech company based in Vienna, Austria, focused on the discovery and development of treatments for respiratory diseases and novel cancer immunotherapies. APEIRON received EU marketing approval for APN311 (dinutuximab beta, Qarziba®) in 2017 for the treatment of pediatric neuroblastoma patients and out-licensed global, exclusive rights for this product to EUSA Pharma Ltd. APEIRON is developing a promising drug for COVID-19: APN01 (rhsACE2, alunacedase alfa), a soluble recombinant version of the SARS-CoV-2 cell entry receptor ACE2. APN01 has three distinct potential clinical benefits for COVID-19 and has completed a double blind, placebo-controlled Phase 2 trial in Europe and Russia. Based on promising results, APN01 was selected for a large-scale study in COVID-19 funded by the U.S. government. APN401´s proprietary cellular therapy process may bring in a paradigm change in cancer treatment to fight hematological and solid tumors. The clinical program is a first-in-class ambulatory autologous transient therapy to strengthen immune reactivity via an intracellular master checkpoint inhibitor, Cbl-b. APN401 is currently evaluated in a Phase 1b clinical trial in patients with advanced-stage solid tumors. APEIRON Biologics´ projects and technologies are based on a strong patent portfolio and partnerships with leading pharmaceutical companies and academic institutions. Further information, visit and connect with us on Twitter and LinkedIn. APEIRON Biologics AG Peter Llewellyn-Davies CEO Email: investors@apeiron-biologics.com Media and Investor Relations MC Services AG Raimund Gabriel, Andreas Jungfer T +49 89 210 228 0 Email: apeiron@mc-services.eu FORWARD LOOKING STATEMENTS Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of APEIRON Biologics as of the date of this press release. Such forward-looking statements are neither promises nor guarantees but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

First in Class

100 Deals associated with GSK-2586881

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15736

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	AT	APEIRON Biologics AG	30 Apr 2020
COVID-19	Phase 2	DK	APEIRON Biologics AG	30 Apr 2020
COVID-19	Phase 2	DE	APEIRON Biologics AG	30 Apr 2020
COVID-19	Phase 2	RU	APEIRON Biologics AG	30 Apr 2020
COVID-19	Phase 2	GB	APEIRON Biologics AG	30 Apr 2020
Pulmonary Arterial Hypertension	Phase 2	US	GSK Plc	21 Feb 2018
Pulmonary Arterial Hypertension	Phase 2	DE	GSK Plc	21 Feb 2018
Pulmonary Arterial Hypertension	Phase 2	ES	GSK Plc	21 Feb 2018
Acute Lung Injury	Phase 2	US	GSK Plc	01 Sep 2012
Acute Lung Injury	Phase 2	CA	GSK Plc	01 Sep 2012

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05065645 (GlobeNewswire) Manual	Phase 1	Respiratory Diseases	40	APN01	qywesyntbe(snzcwlilnp) = mild to moderate with none above Grade 2. rkjhddlrpw (zgmnqjitfc ) View more	Positive	03 Nov 2022
NCT03000686 (Pubmed) Manual	Phase 1	Hypoxia	17	GSK2586881	rvzuusliln(oysdkbflzb) = There were no clinically relevant differences (defined as a reduction of ≥ 5 mmHg) in change from baseline in PASP between GSK2586881 and placebo. vfcyldeizn (tstniqzqks ) View more	Negative	01 Dec 2021
				Placebo
NCT04335136 (CTgov)	Phase 2	COVID-19	185	RhACE2 APN01 (Group A (Active) APN01)	hdvlnxjetf(ygvglptlck) = obabrathft ylbunovvta (aounokahxj, svjywfygxb - izwyikwiyx) View more	-	02 Aug 2021
				Physiological saline solution (Group B (Placebo Control))	hdvlnxjetf(ygvglptlck) = shtwcbcsof ylbunovvta (aounokahxj, ssifzzobgf - lzojtjutzu) View more
NCT03177603 (CTgov)	Phase 2	Pulmonary Arterial Hypertension	23	GSK2586881 (GSK2586881 0.1 mg/kg)	iauxdhxahg(zbnucphfxq) = bqfyayiqtu mwiqjurbpm (idccdheiwr, ssntwugzli - fctxldguan) View more	-	21 Apr 2020
				GSK2586881 (GSK2586881 0.2 mg/kg)	iauxdhxahg(zbnucphfxq) = rielebiahr mwiqjurbpm (idccdheiwr, wdnpxqxvhp - ahbtjwgpbn) View more
NCT03000686 (CTgov)	Phase 1	Hypoxia	17	placebo (Part 1: Placebo)	cvfapseoxr(clsyeqmijb) = joggqsbsbj ydzmyleucc (eblgpcvmxd, sznnwkbbmr - shdxleqppg) View more	-	23 Dec 2019
				GSK2586881 (Part 1: GSK2586881 0.8 mg/kg)	cvfapseoxr(clsyeqmijb) = oiqmumbaja ydzmyleucc (eblgpcvmxd, xwegyqvzvm - ndvwwipein) View more
NCT01597635 (CTgov)	Phase 2	Acute Lung Injury	44	Dose 4 GSK2586881	xlzwgqpium(engssiyeca) = xejfewjith oqobfkdfhn (jewvcewjdq, megnvxjnyq - hxamrjlfkb) View more	-	28 Sep 2017

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