ADC Design Principles


Stable Bioconjugation is a prerequisite of ADC design

Bioconjugation stability is fundamental to ADC stability and this is a core criteria for the design of safe, effective ADCs.

Iksuda uses two bioconjugation platforms in its ADC designs; its own proprietary PermaLink platform, suitable for wild type and engineered antibodies and ConjuAll, in-licensed from LegeoChem Biosciences and specific for engineered antibodies.


Cysteine-specific, stable bioconjugation for WT and engineered antibodies

PermaLink is Iksuda’s proprietary bioconjugation platform, designed to deliver a simple, scalable solution to ADC instability.

Deconjugation resulting in reducing DARs over time and off-target toxicity is inherent to earlier-generation maleimide-based chemistries. Maleimide was used in all earlier-stage ADCs and is still used in many ADCs today.

PermaLink is a vinyl-pyridine based approach which is cysteine-specific and tuneable for payload loading. It enables market leading ADC stability in plasma which helps to reduce off-target toxicity and enhance ADC efficacy.

PermaLink is adaptable for cysteine-based heterogeneous conjugation to wild type antibodies, as well as homogeneous conjugation to antibodies with engineered cysteines. It is compatible with a broad range of payloads.  

PermaLink bioconjugation drives market leading ADC stability

In independent studies, PermaLink-conjugated ADCs are associated with highest stability. 

In the example shown, a PermaLink-ADC (IKS012) is compared for human plasma stability with a ConjuAll site-specific conjugated ADC (IKS03) and a traditional maleimide-conjugated ADC (Adcetris).

PermaLink bioconjugation results in the highest ADC stability, with minimal DAR decrease seen after 7 days. By comparison, Adcetris showed a 55% decrease in DAR in that timeframe, with a 39% decrease evident after 3 days.

Simple, stable, scalable


Site-specific, homogeneous & non-reversible conjugation

ConjuAll is a site-specific homogeneous conjugation platform which incorporates engineered antibodies and enzyme-catalyzed modification steps.

Antibodies are modified to contain a C-terminal CAAX tag and the incorporation of an isoprenoid adapter.

Manufacturing and purification yields stable, homogenous ADCs with DAR2 and minimal aggregation. 

Contact us about partnerships for ADC design & development

Ian Evetts

Chief Business Officer