Antibody drug conjugates (ADCs) and other bioconjugates combine the targeted binding specificity and pharmacological advantages of monoclonal antibodies and other targeted recombinant proteins with the potency advantages of small molecule chemotherapy agents and other therapeutic payloads via conjugation with chemical linkers. With two approved products and a large and growing list of programs in clinical and pre-clinical development, ADCs are emerging as one of the fastest growing development areas in biologic anti-cancer treatment.
While revolutionary, first generation ADCs have a variety of development challenges, including difficulty creating conjugates with a uniform and optimal drug-to-antibody ratio (DAR) for each type of payload, variability in the site of payload conjugation, instability of chemical linkers and poor production efficiency (see FierceBiotech “Targeted Cancer Treatments: A Progress Report”). As ADCs continue to make up an increasing share of the oncology pipeline, there are significant opportunities to leverage recent advances in bioconjugation technology to create the next generation of differentiated ADC therapies to address unmet medical needs.
The SMARTag™ technology platform offers ADC and biologics developers a new toolkit to develop optimized ADCs and bioconjugates. Developed by Redwood Bioscience (acquired by Catalent in 2014), the technology overcomes the limitations associated with conventional protein chemistries that produce heterogeneous products with variable conjugate potency, toxicity and stability. The SMARTag technology enables site-specific, controlled drug-protein conjugation and uses only naturally occurring modifications to proteins requiring minimal cell-line engineering. Developers can now have precise control over conjugate configuration, generating ADCs with optimal efficacy, safety and stability. SMARTag couples a proprietary aldehyde-based conjugation chemistry with proprietary linker chemistries that improve conjugate stability to prevent systemic drug loss, improve targeted delivery of payloads to increase potency, and are capable of counteracting multidrug resistance pathways. SMARTag has demonstrated compatibility with clinically validated ADC payloads including maytansine, auristatin, pyrrolobenzodiazepine (PBD) and duocarmycin, and can also be optimized for use with our partners’ proprietary bioconjugate payloads, including cytotoxics, targeted small molecules, peptides, oligonucleotides, and other therapeutic modalities.