Changing the future of Oncology.
Antibody-Drug Congugates and IADCs
Sutro’s cell-free expression technology provides a rapid and powerful platform for the discovery and development of next generation antibody-drug conjugates (ADCs).
Current ADCs in clinical development have immense promise, but they are limited by the fact that they are structurally heterogeneous populations in which the position and number of conjugated linkers and warheads vary significantly. Such heterogeneity prevents the definition of structure-activity relationships (SARs). Consequently, using traditional ADC technologies prevents researchers from discovering and developing candidates with optimal therapeutic indices and can result in products with unpredictable and sub-optimal pharmacokinetic properties, stability and efficacy.
Sutro can incorporate non-natural amino acids (nnAA) at any site in an antibody structure, thereby allowing for single-species ADCs with site-specific conjugation of linker and warhead. Of vital importance in this process is Sutro’s ability to perform rapid and parallel synthesis of numerous variants taking advantage of a substantial number of different sites, enabling analyses early in discovery to define SARs and locate the best positions for nnAA incorporation based on:
The cell-killing effects of ADCs depend on both the location of the warhead and the drug to antibody ratio. Sutro can control both of these variables with exquisite specificity, resulting in truly optimized product candidates. To address the challenge of manufacturing nnAA-containing ADCs, Sutro has engineered additional versions of cell-free extract that achieve high rates of incorporation of nnAAs and developed chemistries that allow for efficient and stable conjugation of linker/warheads to antibodies.
We have also expanded our ADC technology platform to include tumor targeting immunostimulant ADCs, or IADCs. Our XpressCF+™ Platform has enabled a breakthrough technology to engineer homogeneous, dually conjugated immunostimulant and cytotoxic warheads on a single ADCmolecule. Our novel IADC design is intended to deliver two different drugs directly to the tumor, and not only kill tumor cells but also locally prime an immune response to the patient’s particular tumor cells. We believe that our IADC approach creates a new therapeutic opportunity by combining the best features of an ADC with the biology of a personalized vaccine.