PaSmax® – (P)ayload (a)nd (S)olubility (max)imization – is a branched, PEG-based linker to connect small-molecules to biologics in unequal ratio.
The technological basis of PaSmax® is a core branching unit to which functional entities can be attached according to the chemical and technical needs. Whereas traditional linear conjugations result in 1 : 1 ratios between the two connected entities, the use of PaSmax® allows the attachment of 3 or even 6 small-molecules at once, e.g., toxins or therapeutic drugs, to the biological moiety. Moreover, due to the PEG serving as solubility modulator, even highly hydrophobic small-molecules such as paclitacel can be kept in aqueous solution. Thus, PaSmax® is the ideal linker to increase the payload of biologics with small-molecule drugs. For example, antibody drug conjugates (ADCs) for off-cancer ADC applications are particularly suited for PaSmax® since non-conventional drug-antibody ratios (DARs) of up to 24 are easily achieved.
Furthermore, by using mono-dispersed PEG chains for the attachment to the branching unit, large single molecule PaSmax® reagents can be produced. The unique properties of PaSmax® are summarized in the following table.
|One payload per attachment site
|ADCs with high payload available
|Organic co-solvents often mandatory for conjugation
|Organic solvent-free preparation of the ADCs
|Short & poorly soluble linker
|Improved solubility of the drug
|High risk of aggregation
|Low risk of aggregation
|Challenging quality analytics
|Reduced process complexity
PaSmax® is covered by patent application EP2913064 A1.