Hydrophilic linker platform

The efficiency of ADCs as therapeutic agents against cancer relies on several key parameters such as plasmatic stability, Drug-Antibody Ratio (DAR), position of the drug-linker couple on the antibody or overall hydrophobicity. Hydrophobicity has indeed revealed itself to be an important physicochemical parameter, directly influencing ADCs pharmacokinetics. Drugs used for cancer treatments protocols are highly hydrophobic, which prevents from loading numerous molecules on an antibody.

It has long been considered that a 2-to-4 cytotoxic payload per antibody ratio (DAR 2-4) achieves the optimal balance between physicochemical properties (aggregation propensity), pharmacokinetics and in vivo potency. Our approach aims to overcome this DAR2-4 limitation and paves the way to a new generation of highly-loaded and highly hydrophilic ADCs.
Mablink’s approach to build next generation Antibody-Drug Conjugates (ADCs) relies on a proprietary hydrophilic chemical linker platform which confers hydrophobicity masking properties to the drug linker couple. This technology dramatically decreases the local hydrophobicity of each payload, and hence the overall hydrophobicity of the ADC, which improves pharmacokinetics and/or drug-loading of the conjugate. Our approach allows the formulation of plasma-stable homogeneous ADCs without the requirement of site-specific conjugation technologies.

Learn more about our ADC technology by reading our preprint article available online on ChemRxiv.


High DAR up to 8-16

Masking the apparent hydrophobicity of the cytotoxic payloads allows for high DAR values without significant ADC aggregation nor negative impact on pharmacokinetics. The linker is synthesized using a non-polymeric approach. MW is about 2.0 kDa depending on the payload.

No mAb re-engineering - No tedious enzymatic coupling

Our technology is compatible with any IgG without mAb or cell-line re-engineering. No tedious, expensive and time-consuming enzymatic coupling, remodeling steps or two-step coupling procedures are necessary to produce the ADC.

No premature release of the payload​

Plasma stable cysteine coupling chemistry prevents premature cleavage and albumin transfer of the cytotoxic payload in the bloodstream, decreases systemic toxicity and improves therapeutic index.


Homogeneous ADCs

HIC of interchain cysteine-linked ADC shows no DAR 0, 2, 4, 6 or 8 heterogeneous distribution and low retention time despite high drug load. Long exposure time indicates less non-antigen mediated clearance and improved therapeutic index.
cytotoxic payloads

Compatible with virtually any payload

Our coupling procedure is compatible with very hydrophobic payloads (validated with MMAE, SN38, PNU-159682 or Exatecan, among others), as well as enzyme-cleavable or non-cleavable linker designs, and opens the way to the use of novel cytotoxic compounds with new mechanisms of action as potent ADC payloads.

No aggregation and improved manufacturability

Our SN38-based homogeneous DAR16 ADC, incorporating our technology, shows absolutely no aggregation of the conjugates despite high drug load. Our technology leads to very hydrophilic conjugates involving water-soluble drug-linkers with improved manufacturability. Free payload purification is also straightforward by simple dialysis or TFF.

Hydrophilic chemistry

Chemistry is optimized for high hydrophilicity and therefore requires no unnecessary, bulky or hydrophobic moieties. Drug-linkers are monodisperse (single molecular weight, non-polymeric approach).  Molecular weight of drug-linker is approx. 2kDa, depending on the toxic payload, and easy to scale-up using classic organic chemistry methodologies.