Protein scaffold linker payload6/18/2023 Regulatory filings will be a combination of small molecule and biologics. New analytical methodologies are required for the ADCs, supplementing those used for the antibody itself. ADCs offer some interesting physicochemical properties, due to conjugation itself, and to the (often) hydrophobic payloads that must be considered during their CMC development. The latter aim to be better characterized and controlled, with wider therapeutic indices as well as improved pharmacokinetic-pharmacodynamic (PK-PD) profiles. As the first generation of ADCs utilizing lysine and cysteine chemistries moves through the clinic and into commercialization, second generation ADCs involving site specific conjugation technologies are being evaluated and tested. Novel linker technologies have been synthesized and highly potent cytotoxic drug payloads have been created. Advances in antibody science has enabled identification and generation of high affinity, highly selective, humanized or human antibodies for a given target. Design and development of ADCs requires the synergistic combination of the monoclonal antibody, the linker and the payload. The convergence of advanced understanding of biology with chemistry has led to a resurgence in the development of antibody-drug conjugates (ADCs), especially with two recent product approvals.
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