Mechanism of action

The melflufen MoA Story

Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers.

  • 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.