solnatide (AP-301) / APEPTICO - LARVOL DELTA

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: Apeptico Forschung und Entwicklung GmbH | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Respiratory Diseases

Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein. (PubMed, Front Immunol) - "solnatide, AP301) -which directly activates ENaC upon binding to its a subunit- can override RBD-induced impairment of ENaC function and hACE2 expression, mitigates ROS and TF generation and restores barrier function in HL-MVEC monolayers. In correlation with the increased mortality observed in COVID-19 patients co-infected with S. pneumoniae, compared to subjects solely infected with SARS-CoV2, we observe that prior intraperitoneal RBD treatment in transgenic mice globally expressing hACE2 significantly increases fibrin deposition and capillary leak upon intratracheal instillation of S. pneumoniae and that this is mitigated by TIP peptide treatment."

Journal • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • ACE2

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: Apeptico Forschung und Entwicklung GmbH | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date

The Epithelial Sodium Channel-An Underestimated Drug Target. (PubMed, Int J Mol Sci) - "The EMA- and FDA-designated orphan drug solnatide is currently being tested in phase 2 clinical trials in the setting of acute respiratory distress syndrome, and the NOX1/ NOX4 inhibitor setanaxib is undergoing clinical phase 2 and 3 trials for therapy of primary biliary cholangitis, liver stiffness, and carcinoma. The established ENaC blocker amiloride is mainly used as an add-on drug in the therapy of resistant hypertension and is being studied in ongoing clinical phase 3 and 4 trials for special applications. This review focuses on discussing some recent developments in the search for novel therapeutic agents."

Journal • Review • Acute Respiratory Distress Syndrome • Cardiovascular • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hepatology • Hypertension • Immunology • Nephrology • Oncology • Primary Biliary Cholangitis • Pulmonary Disease • Respiratory Diseases • NOX4

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints. (PubMed, Front Immunol) - "In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain."

Journal • Acute Lung Injury • Glomerulonephritis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus Nephritis • Nephrology • Oncology • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: Apeptico Forschung und Entwicklung GmbH | Trial completion date: May 2022 ➔ Jun 2023 | Trial primary completion date: May 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date

A Phase 2 Study to Evaluate the Safety and Efficacy of VS-505(AP301) to Treat Hyperphosphatemia in Hemodialysis Patients (clinicaltrials.gov) - P2 | N=158 | Active, not recruiting | Sponsor: Shanghai Alebund Pharmaceuticals Limited | Trial completion date: Aug 2022 ➔ Dec 2022

Trial completion date • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Conformational ensemble of the TNF-derived peptide solnatide in solution. (PubMed, Comput Struct Biotechnol J) - "TIP peptide, AP301) is a 17-mer cyclic peptide that mimics the LLD of human TNF which activates the amiloride-sensitive epithelial sodium channel (ENaC) and, as such, recapitulates the capacity of TNF to enhance alveolar fluid clearance, as demonstrated in numerous preclinical studies. Using the structural information determined here and also that available for the ENaC protein, we propose a model to describe solnatide interaction with the C-terminal domain of the ENaCα subunit. This model may serve to guide future experiments to validate specific interactions with ENaCα and the design of new solnatide analogs with unexplored functionalities."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Oncology • Pulmonary Disease • Respiratory Diseases • TNFA

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate to severe ARDS in a randomized, placebo-controlled, double-blind trial: preliminary evaluation of safety and feasibility in light of the COVID-19 pandemic. (PubMed, Trials) - "The DSMB and the investigators did not find any evidence that patients suffering from ARDS due to SARS-CoV-2 may be at higher (or generally altered) risk when included in the trial, nor were there indications that those patients might influence the integrity of the study data altogether. For this reason, a continuation of the phase IIB clinical study activities can be justified. Researchers continuing clinical trials during the pandemic should always be aware that the exceptional circumstances may alter study results and therefore adaptations of the study design might be necessary."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Septic Shock

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS-a randomized, placebo-controlled, double-blind trial. (PubMed, Trials) - P2 | "The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion."

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

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS (clinicaltrials.gov) - P2; N=80; Recruiting; Sponsor: Apeptico Forschung und Entwicklung GmbH; Trial completion date: Dec 2020 ➔ May 2022; Trial primary completion date: Dec 2020 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date

"LISAvienna Newsletter, December 15, 2020 - @HookipaPharma @enGenesBiotech @AresGenetics @Boehringer @ProxygenTx @phagomed @apeironbio @valnevaSE @symptoma @eveliqure @solnatide @lexogen @EBDgroup @EuroBiotechNews @viennabiocenter @HorizonEurope1 https://t.co/3dabrZQyTP" (@lifesciencevie)

COVID-19: Efficacy of solnatide to treat pulmonary permeability oedema in SARS-Cov-2 positive patients with moderate-to-severe ARDS COVID-19: Wirksamkeit von Solnatide zur Behandlung des pulmonalen Permeabilitätsödems bei SARS-Cov2 positiven Patienten mit mäßigem bis schwerem akutem Atemnotsyndrom (ARDS) – eine randomisierte, Placebo kontrollierte Doppelblindstudie (clinicaltrialsregister.eu) - P2; N=40; Ongoing; Sponsor: Department of Clinical Pharmacology, Medical University of Vienna, Vienna Austria

Clinical • New P2 trial