Best-in-class antibody drug conjugation technology
Ambrx’s technologies enable a rational, structure-based approach to create novel antibody-drug conjugates (ADCs) that are optimized at multiple levels: site of drug attachment, properties of the mAb, and specificity of binding, delivery, uptake and release of the drug within the diseased cell or tissue.
The ability to incorporate a non-natural amino acid at a precise position in a protein or mAb allows the use of novel conjugation chemistries that are not reactive with the native amino acids. These new chemistries allow for the introduction of novel and highly stable drug linkers that can be further tuned for the desired properties. Furthermore, this site-specific approach allows for the generation of homogenous (>95% single species and defined DAR) conjugates and enables a rational, reiterative optimization of efficacy, tolerability, bioavailability and biophysical (drug-like) properties. In turn, this understanding of how to generate optimized ADCs has allowed us to move beyond oncology into indications where a safer, more specific drug conjugate is required. To fully leverage our ADC platform, in addition to our site-specific linkage technology we have created novel payloads and linkers that better address the disease indication. Ambrx technologies allow us to expand the range of payloads in other therapeutic indications beyond cytotoxic moieties into those that are agonists or antagonists or those that selectively modify signaling pathways in other therapeutic indications.
Ambrx ADC showing site-specific conjugation:
We and our collaboration partners have generated data sets that demonstrate that Ambrx’s proprietary drug conjugates hold significant advantages over conjugates made using conventional technologies that are randomly aimed at cysteine or lysine residues. These include clear evidence of improved potency with greater tolerability (wider therapeutic index), increased stability of the drug linker, extended half-life that reflects that of the parent antibody and better biophysical properties.