Delving into the Latest Updates on Solnatide with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

TIP-PEPTIDE

Target

ENaC

Action

agonists

Mechanism

ENaC agonists(Epithelial sodium channel agonists)

Therapeutic Areas

Respiratory DiseasesOther Diseases

Active Indication

Pulmonary EdemaRespiratory Distress SyndromeAcute Lung Injury

Inactive Indication

PseudohypoaldosteronismReperfusion Injury

Originator Organization

Vrije Universiteit Brussel

Active Organization

APEPTICO Forschung & Entwicklung GmbHMediolanum SpA

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC82H119N23O27S2

InChIKeyLKVFMOMQYXIFRK-KSVAIKAXSA-N

CAS Registry259206-53-6

Sequence Code 54499

Source: *****

This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS and review potential efficacy endpoints for a future phase III pivotal trial.

Start Date23 May 2018

Sponsor / Collaborator

APEPTICO Forschung & Entwicklung GmbH

EUCTR2017-003855-47-AT

/ Not yet recruitingPhase 2

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability oedema in patients with moderate-to-severe ARDS - a randomised, placebo-controlled, double-blind trial

Start Date27 Feb 2018

Sponsor / Collaborator

APEPTICO Forschung & Entwicklung GmbH

100 Clinical Results associated with Solnatide

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100 Translational Medicine associated with Solnatide

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100 Patents (Medical) associated with Solnatide

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25

Literatures (Medical) associated with Solnatide

24 Apr 2023·International journal of molecular sciences

The Epithelial Sodium Channel-An Underestimated Drug Target

Review

Author: Lemmens-Gruber, Rosa ; Tzotzos, Susan

Epithelial sodium channels (ENaC) are part of a complex network of interacting biochemical pathways and as such are involved in several disease states. Dependent on site and type of mutation, gain- or loss-of-function generated symptoms occur which span from asymptomatic to life-threatening disorders such as Liddle syndrome, cystic fibrosis or generalized pseudohypoaldosteronism type 1. Variants of ENaC which are implicated in disease assist further understanding of their molecular mechanisms in order to create models for specific pharmacological targeting. Identification and characterization of ENaC modifiers not only furthers our basic understanding of how these regulatory processes interact, but also enables discovery of new therapeutic targets for the disease conditions caused by ENaC dysfunction. Numerous test compounds have revealed encouraging results in vitro and in animal models but less in clinical settings. 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.

01 Jan 2023·Frontiers in immunology

Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein.

Article

Author: Fulton, David ; Hamacher, Jürg ; Fischer, Bernhard ; Mraheil, Mobarak A ; Sridhar, Supriya ; Zeitlinger, Markus ; Eaton, Douglas C ; Singla, Bhupesh ; Annex, Brian H ; Romero, Maritza J ; Csanyi, Gabor ; Moseley, Auriel S ; Song, Chang ; Chakraborty, Trinad ; Yue, Qian ; Gan, Lin ; Lucas, Rudolf

IntroductionAlthough both COVID-19 and non-COVID-19 ARDS can be accompanied by significantly increased levels of circulating cytokines, the former significantly differs from the latter by its higher vasculopathy, characterized by increased oxidative stress and coagulopathy in lung capillaries. This points towards the existence of SARS-CoV2-specific factors and mechanisms that can sensitize the endothelium towards becoming dysfunctional. Although the virus is rarely detected within endothelial cells or in the circulation, the S1 subunit of its spike protein, which contains the receptor binding domain (RBD) for human ACE2 (hACE2), can be detected in plasma from COVID-19 patients and its levels correlate with disease severity. It remains obscure how the SARS-CoV2 RBD exerts its deleterious actions in lung endothelium and whether there are mechanisms to mitigate this.MethodsIn this study, we use a combination of in vitro studies in RBD-treated human lung microvascular endothelial cells (HL-MVEC), including electrophysiology, barrier function, oxidative stress and human ACE2 (hACE2) surface protein expression measurements with in vivo studies in transgenic mice globally expressing human ACE2 and injected with RBD.ResultsWe show that SARS-CoV2 RBD impairs endothelial ENaC activity, reduces surface hACE2 expression and increases reactive oxygen species (ROS) and tissue factor (TF) generation in monolayers of HL-MVEC, as such promoting barrier dysfunction and coagulopathy. The TNF-derived TIP peptide (a.k.a. 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.

01 Dec 2022·Trials

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

Letter

Author: Zwissler, Bernhard ; Schmid, Benedikt ; Lucas, Rudolf ; Frank, Sandra ; Kranke, Peter ; Meybohm, Patrick

AbstractBackgroundIn May 2018, the first patient was enrolled in the phase-IIb clinical trial “Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Edema in Patients with Moderate to Severe ARDS.” With the onset of the COVID-19 pandemic in early 2020, the continuation and successful execution of this clinical study was in danger. Therefore, before the Data Safety Monitoring Board (DSMB) allowed proceeding with the study and enrollment of further COVID-19 ARDS patients into it, additional assessment on possible study bias was considered mandatory.MethodsWe conducted an ad hoc interim analysis of 16 patients (5 COVID-19- ARDS patients and 11 with ARDS from different causes) from the phase-IIB clinical trial. We assessed possible differences in clinical characteristics of the ARDS patients and the impact of the pandemic on study execution.ResultsCOVID-19 patients seemed to be less sick at baseline, which also showed in higher survival rates over the 28-day observation period. Trial specific outcomes regarding pulmonary edema and ventilation parameters did not differ between the groups, nor did more general indicators of (pulmonary) sepsis like oxygenation ratio and required noradrenaline doses.ConclusionThe 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.

100 Deals associated with Solnatide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12136

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Edema	Phase 2	Germany	APEPTICO Forschung & Entwicklung GmbH	23 May 2018
Pulmonary Edema	Phase 2	Austria	APEPTICO Forschung & Entwicklung GmbH	23 May 2018
Respiratory Distress Syndrome	Phase 2	Austria	APEPTICO Forschung & Entwicklung GmbH	23 May 2018
Respiratory Distress Syndrome	Phase 2	Germany	APEPTICO Forschung & Entwicklung GmbH	23 May 2018
Acute Lung Injury	Phase 2	-	Mediolanum SpA	-
Reperfusion Injury	Preclinical	Austria	APEPTICO Forschung & Entwicklung GmbH	24 May 2013
Pseudohypoaldosteronism	Preclinical	Austria	APEPTICO Forschung & Entwicklung GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ATS2024	Not Applicable	Pulmonary Edema	-	TIP peptide	bcmdmovkxw(jbhfnbevij) = qxnnvjvwrf bxhkawtmcl (nhbvxtidat ) View more	-	19 May 2024
				TIP Peptide (Control lungs without bacteria)	bcmdmovkxw(jbhfnbevij) = hgcakdubod bxhkawtmcl (nhbvxtidat ) View more
ERS2011	Not Applicable	Influenza A virus infection	-	TIP peptide	(iaxrzkwsfr) = xgcwonwcch wceijazqil (bjxrhcxlcw ) View more	-	01 Sep 2011
				Ro32-4032	(esqunzmesz) = husdtxhufh ntspfsmbju (iagypikchf )

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Biosimilar

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