About NP-120 (Ifenprodil)
The Company’s lead compound in its idiopathic pulmonary fibrosis (IPF) research program, is a drug called Ifenprodil, an orally delivered small molecule, which was originally developed by Sanofi to treat peripheral circulatory disorders. Algernon conducted two independent studies showing that NP-120 (Ifenprodil) outperformed the world’s leading two treatments for IPF, Nintedanib and Pirfenidone in a recent pre-clinical in vivo animal study, reducing fibrosis by 56% with statistical significance.
Since NP-120 (Ifenprodil) is already approved with an established safety history, Algernon intends to move the drug directly into a phase II human trial. The Algernon business model is to repurpose safe approved drugs that are not available in the US or Europe, screen them in globally accepted animal models for new diseases, file new intellectual property rights and then move them into an off label phase II trial in the country where they were originally approved. Once a signal is established in a human trial, the company will begin to advance the repurposed drug through a USFDA registration.
NP-120 (Ifenprodil) is an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist specifically targeting the NMDA-type subunit 2B (Glu2NB). Ifenprodil also exhibits agonist activity for the Sigma-1 receptor, a chaperone protein up-regulated during endoplasmic reticulum stress. The company is currently investigating the mechanism of action as it relates to IPF.
NP-120 (Ifenprodil – brand name Cerocal) was initially developed by Sanofi in the 1990s in the French and Japanese markets for the treatment of circulatory disorders. Although no longer available in France, the drug is highly genericized and still sold in Japan.
Potential Drug Class Effect
The Company also tested NP-121 (Radiprodil), which possess a similar phenylethanolamine pharmacophore as NP-120 (Ifenprodil), in its initial IPF in vivo animal study. In the study, both compounds, at the same dose, reduced fibrosis to a similar extent. This data established an early indication that this could be a potential drug class effect and not unique to NP-120 (Ifenprodil) alone. NP-121 (Radiprodil) was originally developed by Gideon Richter and Forest labs and reached Phase III trials for the treatment of diabetic nephropathy. The French pharmaceutical firm UCB, having acquired the development rights, have been recently testing NP-121 (Radiprodil) for the treatment of drug-resistant infantile spasms. Other compounds targeting the Glu2NB pathway that have been tested in the clinic included EVT-101 (Evotech/Roche) and MK-0657.
Data from this recent study demonstrated a statistically significant improvement in established fibrosis in a 21-day bleomycin mouse model (treatment began on Day 7):
- Pirfenidone (100 mg/kg, BID), both a positive control and comparator arm in the study, showed a 44% reduction in fibrosis vs untreated controls (not statistically significant) as measured by Trichrome staining and modified Ashcroft scoring.
- Nintedanib (40 mg/kg, QD), a second positive control and comparator arm, and NP-251 (30 mg/kg, TID) both showed a 51% reduction in fibrosis vs untreated controls (p<0.05).
- NP-120 (20 mg/kg, TID) showed a 56.0% reduction in fibrosis vs untreated controls (p=0.015).