MMAF (monomethyl auristatin F) is a synthetic antimitotic agent derived from dolastatin 10, a natural product originally isolated from the marine sea hare Dolabella auricularia. MMAF differs from MMAE by the substitution of a charged phenylalanine residue at its C-terminus, instead of the uncharged N-methyl valine present in MMAE. The additional charged group makes MMAF more hydrophilic and less membrane-permeable than MMAE. This property reduces the “bystander effect” (damage to neighboring, non-target cells) and may also lower potency compared to MMAE when target-cell internalization or linker cleavage is inefficient.
Belantamab mafodotin (Blenrep®), approved in 2020 and marketed by GlaxoSmithKline plc, is the first FDA-approved ADC using MMAF as its payload. It employs a non-cleavable maleimidocaproyl (mc) linker with an average drug-to-antibody ratio (DAR) of 4. Several other ADC candidates in clinical trials also utilize MMAF with various antibodies and linkers targeting cancers such as breast, ovarian, and hematologic malignancies.
The AqT®-MMAF (CM81306) drug asset is currently available for customer evaluation using reduced-thiol chemistry with a releasable VC-PAB linker. This design enables efficient loading of up to eight drug molecules per antibody with minimal aggregation and improved stability.