Most of the challenges of ADCs are linked to the hydrophobicity of the cytotoxic drugs used, which degrade the pharmacological properties of the antibody when attached to it.
Our PSARlink™ platform “masks” the hydrophobicity of the cytotoxic drugs by adding a chain of polysarcosine on the linker, which dramatically improves the pharmacological properties of ADCs, restoring the pharmacokinetics (PK) profile of the native antibody, even with DAR8 (8 cytotoxic drugs per antibody) ADCs.
Designing DAR8 ADCs enables the use of slightly less potent drugs with differentiated mechanisms of action, like the topoisomerase I inhibitors of the camptothecin derivatives family, and/or addressing tumors with lower target expression.
The restored PK profile corresponds to an increase in the drug exposure (better efficacy) and a decreased rate of non-antigen mediated clearance of the ADCs (protecting clearance organs such as the liver).
Mablink uses plasma-stable linkers to prevent premature deconjugation and therefore lower the non-specific toxicity.
Mablink has completed several proof-of-concept experiments demonstrating that PSARlink™-based ADCs show a higher efficacy against tumors and a much higher tolerability than previous generations of ADCs.