Fosmanogepix is a unique antifungal therapy with a novel mechanism of action and broad spectrum activity, including to strains that are resistant to standard of care therapy. Fosmanogepix is currently in Phase 2 clinical trials evaluating the efficacy and safety of both intravenous (IV) and oral formulations for the treatment of patients with fungal infections caused by aspergillosis and candidemia, including candidemia caused by C. auris.
In Phase 1 trials, both IV and oral formulations of fosmanogepix were well-tolerated with a favorable safety profile at clinically effective doses. Both formulations have a low propensity for clinically important drug-drug interactions. In vitro studies have demonstrated that manogepix, the active moiety of fosmanogepix, has activity against echinocandin-resistant Candida, azole-resistant Aspergillus, and multidrug-resistant fungi, and can be widely distributed to various tissues including the brain, lung, kidney and eye. With both IV and oral formulations, Fosmanogepix allows for a convenient transition from IV to oral, and continuation of care outside of the hospital.
Fosmanogepix has a novel mechanism of action that inhibits the highly conserved fungal enzyme Gwt1, which is essential for trafficking and anchoring mannoprotein to the outer cell wall in fungi. Mannoproteins are required for fungal cell wall integrity, adhesion, pathogenicity, and for evading the host immune system. Fosmanogepix does not inhibit the closest human homolog to Gwt1m, the PIGW protein, and as a result, fosmanogepix compromises the growth of fungal pathogens without harming healthy cells of patients.