AM1476 For Treatment Of Systemic Sclerosis

AM1476 is an oral, small molecule, selective, high-affinity 5-HT_2B receptor antagonist which modulates key fibrotic pathways (TGF-β and Wnt).

Unlike agonists, antagonists only act when the endogenous agonist is active, in this case serotonin (5-HT). Molecules downstream of the 5-HT pathways, for example, TGF-β are only affected by the antagonist when 5-HT is active, which should also minimize adverse events.

The anti-fibrotic efficacy of AM1476 has been clearly demonstrated in several well-known preclinical state-of-the-art models of fibrosis:

●    AM1476 halted and reversed the progression of pre-established fibrosis in skin and lung tissue.

●    AM1476 ameliorates several processes related to fibroblast and macrophage activation in disease models of fibrosis.

A Phase I Study has been successfully concluded. It was a double-blind, randomized, placebo-controlled design, investigating the safety and pharmacokinetics of AM1476 in healthy subjects. AM1476 was found to be safe and well tolerated at all investigated doses.

A Phase II study has been designed to evaluate the treatment effects in patients, initially focusing on diffuse cutaneous systemic sclerosis interstitial lung disease. Active product ingredient (API) will be ready as cGMP materials for this Phase II study.

AM1476 is designed to be orally administered as a tablet and used as monotherapy or in combination treatments.

Together with our well-designed molecule, we plan to offer a novel genetic marker approach using a gene signature to identify responders to treatment.

Orphan Drug Designation application for systemic sclerosis is being prepared for submission to FDA and EMA.