Rational Drug Design of New Chemical Entities.
New Chemical Entity
GED-0507-34-Levo (Code: GED-0507) is a patent protected New Chemical Entity, under development by Nogra Pharma for the treatment of Idiopathic Pulmonary Fibrosis (IPF) as main indication, and having the treatment of post-COVID-19 lung inflammation and fibrosis as possible additional indication.
GED-0507 is a new well tolerated amino-phenyl-methoxy-propionic acid, that was originally designed with the aim of obtaining a safe anti-inflammatory compound for the treatment of Ulcerative Colitis.
GED-0507 has completed the nonclinical development stage and is ready to enter the clinical development stage.
Timeline
Target ID
Lead ID & Preclinical
Formulation Development
Clinical Phase l
Clinical Phase lI
Clinical Phase lII
Market
GED-0507
Anti-inflammatory activity
Its anti-inflammatory activity was demonstrated in mouse models of colitis and in vitro in:
a) intestinal epithelial cell lines,
b) in a sebocyte cell line, and
c) in primary human keratinocytes.
Anti-fibrotic effects
Anti-fibrotic effects were first demonstrated in a mouse model of inflammation-driven intestinal fibrosis and in vitro in primary human intestinal fibroblasts from Ulcerative Colitis (UC) patients. (https://doi.org/10.1097/MIB.0000000000000618)
Moreover, in the bleomycin-induced lung fibrosis mouse model, GED-0507 was able both in a preventive and in a therapeutic mode, to significantly reduce lung fibrosis. Statistically significant results were obtained on several endpoints versus either pirfenidone or nintedanib, the two products approved for the treatment of IPF. (https://doi.org/10.1038/s41423-020-0394-y)
Then, the activity of GED-0507 on various inflammatory/ fibrotic pathways was further evaluated GED-0507 in the BLM mouse model reduced the expression of markers of inflammation and of fibrosis, and inhibited epithelial-to-mesenchimal transition. (https://doi.org/ 10.1371/journal.pone.0257281)
Idiopathic Pulmonary Fibrosis
Based on the collected data, GED-0507 obtained by EMA in 2018 the Orphan Drug Designation for the treatment of Idiopathic Pulmonary Fibrosis (Community Register of Orphan Medicinal Products No.EU/3/18/2056) on the grounds of the Sponsor having provided “sufficient justification for the assumption that the medicinal product containing GED-0507 will be of significant benefit to those affected by the condition”.
GED-0507 has completed the nonclinical development stage and is ready to enter the clinical development stage for IPF.
An immediate-release oral solid dosage form (tablet) has been developed for the treatment of IPF in two dose strengths of 250 and 500 mg GED-0507/tablet.
The available comprehensive package of nonclinical and clinical safety data support the initiation of a Phase Ib chronic study in patients affected by IPF.
SARS-CoV-2
More recently, data have been gathered which support the possible use of GED-0507 for lung injury caused by SARS-CoV-2 virus.
SARS-CoV2 uses the ACE2 receptor for its internalization,
- The effects of GED-0507 have been evaluated on the expression of the anti-inflammatory receptor ACE2 and other key inflammatory mediators expressed during COVID-19 disease in a murine model of lung inflammation/fibrosis induced by bleomycin.
- New biological functions of GED-0507 have been identified through an induction of ACE2 and MasR, and the decreased expression of TACE and ERK1.
- Data suggest also that GED could have potential therapeutic efficacy in COVID19 according to its known effects on key factors sustaining SARS-CoV2 pathogenicity in vulnerable patients.