Mechanism of action of melflufen

The melflufen MoA Story

Melflufen (Ygalo®), an peptide cojugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action.

  • Aminopeptidases are heavily over-expressed in MM and are key to the transformational process of the tumor cells.
  • Melflufen selectively targets MM through aminopeptidase-driven accumulation; in vitro experiments show a 50-fold enrichment of alkylating metabolites in MM cells.
  • The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Comparing clinical data between melflufen and the current standard of care in multiple myeloma patients indicates that treatment with melflufen increases overall survival, progression free survival and the number of patients with significant tumour burden reduction as well as being better tolerated by patients.