alunacedase alfa (APN01) / Apeiron Biologics - LARVOL DELTA

Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research. (PubMed, Rev Cardiovasc Med) - "The current overview presents the latest research findings on the mechanisms through which novel anti-hypertensive medications target the RAS. These include zilebesiran (targeting angiotensinogen), PRO20 (targeting the renin/(pro)renin/PRR axis), sacubitril/valsartan (targeting the renin/ACE/Ang II/AT1R axis), GSK2586881, Ang (1-7) and AVE0991 (targeting the renin/ACE2/Ang (1-7)/MasR axis), alamandine (targeting the alamandine/MrgD receptor axis), C21 and β-Pro7-Ang III (targeting the renin/ACE/Ang II/AT2R axis), EC33, and firibastat and NI956 (targeting brain Ang III)."

Journal • Review • Cardiovascular • CNS Disorders • Hypertension • Vascular Neurology

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2. (PubMed, ERJ Open Res) - P1 | "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."

Journal • P1 data • PK/PD data

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer. (PubMed, PLoS One) - P1 | "Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled APN01 Developed as Treatment for COVID-19 (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Apeiron Biologics | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants. (PubMed, EMBO Mol Med) - "Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01)...Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension. (PubMed, Pulm Circ) - P2 | "GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1-7) and angiotensin (1-5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined."

Journal • PK/PD data • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled APN01 Developed as Treatment for COVID-19 (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Apeiron Biologics | Trial completion date: Jan 2022 ➔ Jun 2022 | Trial primary completion date: Jan 2022 ➔ Jun 2022 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

NECTAR: Novel Experimental COVID-19 Therapies Affecting Host Response (clinicaltrials.gov) - P2/3; N=1600; Recruiting; Sponsor: Vanderbilt University Medical Center; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: May 2022 ➔ May 2023

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Peptides-based therapeutics: Emerging potential therapeutic agents for COVID-19. (PubMed, Therapie) - "A candidate drug, RhACE2-APN01 based on recombinant hACE2 peptide has already entered phase II clinical trials. This review sheds light on different aspects of the feasibility of using peptide-based therapeutics as the promising therapeutic route for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled APN01 Developed as Treatment for COVID-19 (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: Apeiron Biologics

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study. (PubMed, Pulm Ther) - "A single IV dose of GSK2586881 0.8 mg/kg was well tolerated but did not impact the acute HPV response in healthy volunteers."

Clinical • Journal • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

APEIRON Biologics' APN01 selected for large-scale US trial in COVID-19 (Yahoo Sports) - "APEIRON was invited to participate in the US ACTIV-4d RAAS trial...APEIRON's specific recombinant human ACE2 (rhACE2), APN01, was prioritized for study by a broad panel of clinical trial experts...The trial is anticipated to begin in Q2-2021....The randomized, double-blinded, placebo controlled ACTIV-4d RAAS trial will enroll approximately 1,600 hospitalized patients with COVID-19, at more than 50 individual sites....APEIRON is preparing a company-sponsored Phase 1 trial to evaluate drug delivery of APN01 through inhalation in order to target all infected or at-risk patients earlier in the course of the disease....A Phase 1 inhalation study will form the basis for further development in chronic respiratory diseases with high unmet medical need such as Chronic Obstructive Pulmonary Disease (COPD) and Pulmonary Arterial Hypertension (PAH). Study start of the inhalation trial is anticipated for Q3-2021."

New P1 trial • New trial • Infectious Disease • Novel Coronavirus Disease

APEIRON's APN01 shows clinical benefits for severely ill COVID-19 patients in phase 2 trial (PharmiWeb) - P2, N=200; NCT04335136; Sponsor: Apeiron Biologics; "The data showed that fewer patients treated with APN01 (n=9) died or received invasive ventilation compared to placebo (n=12), although statistical significance was not achieved due to the low total number of events....The data demonstrated a statistically significant improvement in mechanical ventilator-free days in alive patients and reduction in viral load in the group treated with APN01 compared to placebo. APN01 also demonstrated a positive impact on key biomarkers of the renin angiotensin system (RAS), demonstrating in vivo efficacy of the drug....In the APN01 treatment group, a tendency to faster recovery compared to the control group was observed."

Biomarker • P2 data • Infectious Disease • Novel Coronavirus Disease

APN01-COVID-19: Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (clinicaltrials.gov) - P2; N=200; Completed; Sponsor: Apeiron Biologics; Recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease

APEIRON Biologics: Patient recruitment completed in Phase II COVID-19 Clinical Trial of APN01 (PharmiWeb) - "APEIRON Biologics AG today announced that patient recruitment of its ongoing Phase II clinical trial with APN01 to treat COVID-19 was completed. The results of the international, multicenter, double-blind, randomized and placebo-controlled trial are expected in Q1 2021....'Currently, we are defining with the European Medicines Agency (EMA) a potential rolling Marketing Authorization Application (MAA) submission to make this drug candidate available for severely suffering patients as fast as possible, subject to positive clinical results.'"

Enrollment closed • European regulatory • P2 data • Infectious Disease • Novel Coronavirus Disease

APN01-COVID-19: Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Apeiron Biologics; Trial primary completion date: Sep 2020 ➔ Dec 2020

Clinical • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

THE LANCET publishes promising data of APEIRON's APN01 (rhsACE2) to treat COVID-19 in named patient use (PRNewswire) - P=NA, N=1; "APEIRON Biologics AG today announced that first, encouraging data with its clinical drug candidate APN01 (rhsACE2) to treat severe COVID-19 were published....APN01 (soluble ACE2) infusion showed the expected enzymatic activity and modulation of the renin angiotensin system. The APN01 infusion correlated with a gradual reduction in levels of multiple disease relevant inflammatory mediators over the studied time period. The infusion of APN01 also correlated with a rapid loss of detectable viremia and slightly delayed reduction in viral titers in tracheal samples and nasopharyngeal swaps. APN01 infusion was fully compatible with an adaptive immune response and the development of high titers of neutralizing antibodies against SARS-CoV-2."

Clinical data • Infectious Disease • Novel Coronavirus Disease

Aperion Biologics announces financing round for the further development of the Covid-19 drug APN01 (PharmiWeb) - "APEIRON Biologics AG will complete a capital increase to finance the further development of APN01 for the treatment of severely ill COVID-19 patients....The Vienna Insurance Group (VIG) will lead the financing round and secures the private placement....Austrian Research Promotion Agency (FFG), the Vienna Business Agency (WAW), the Austrian promotional bank (AWS) and the Erste Bank have committed grant....In the ongoing Phase II clinical trial, 200 patients severely affected by COVID-19 are to be treated."

Financing • Infectious Disease • Novel Coronavirus Disease

A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P2; N=25; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Cardiovascular • Hypertension

APN01-COVID-19: Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Apeiron Biologics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

APN01-COVID-19: Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (clinicaltrials.gov) - P2; N=200; Not yet recruiting; Sponsor: Apeiron Biologics

Clinical • New P2 trial

Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19 Rekombinantes humanes Angiotensin-konvertierendes Enzym 2 (rhACE2) als Behandlung für Patienten mit COVID-19 (clinicaltrialsregister.eu) - P2; N=200; Ongoing; Sponsor: APEIRON Respiratory Therapies GmbH

Clinical • New P2 trial • ANGPT1 • ANGPT2 • CRP • CXCL8 • IL6 • TNFRSF1B

Aperion Biologics initiates phase II clinical trial of APN01 for treatment of Covid-19 (GlobeNewswire, APEIRON Biologics) - "APEIRON Biologics AG today announced that it has received regulatory approvals in Austria, Germany and Denmark to initiate a Phase II clinical trial of APN01 to treat COVID-19....The Phase II trial aims to treat 200 severely infected COVID-19 patients, and the first patients are expected to be dosed shortly....The randomized, double-blind Phase II trial will compare APN01 to placebo in up to 200 patients at 10 sites in Austria, Denmark and Germany. The primary objective of the trial is to assess the clinical efficacy and safety of APN01 in severe COVID-19 patients using, among other criteria, the need for invasive mechanical ventilation. Secondary objectives include the evaluation of measurable biological biomarker changes following treatment with APN01."

Clinical protocol • Enrollment status • New trial • Non-US regulatory

"APN01 = recombinant human ACE2. Covid-19 enters human cells via the ACE2 receptor." (@JacobPlieth)

UBC, Apeiron Biologics to trial coronavirus drug candidate in China (Clinical Trials Arena) - "A researcher at the University of British Columbia in Canada has partnered with...Apeiron Biologics to conduct a pilot clinical trial of a new drug candidate to treat disease caused by the new coronavirus, Covid-19, in China....During the study, 24 patients will receive treatment with the drug candidate for seven days....The primary aim of the trial is to assess whether APN01 could decrease the SARS-CoV-2 virus viral load, along with the number of days patients suffer from fever."

New trial