ABBV-787: An Investigational CD33-Targeting BET Degrader Antibody-Drug Conjugate for Acute Myeloid Leukemia - Development Overview and Discontinuation

1. Introduction to ABBV-787

1.1. Overview of ABBV-787

ABBV-787 was an investigational therapeutic agent developed by AbbVie, identified by alternative names such as ABBV 787 and ABBV787.[1] It was classified as an Antibody-Drug Conjugate (ADC), a therapeutic modality engineered for the targeted delivery of a cytotoxic payload directly to cancer cells, with the primary route of administration being intravenous.[1] The principal therapeutic area for ABBV-787 was neoplasms, specifically focusing on Hemic and Lymphatic Diseases, with Acute Myeloid Leukemia (AML) as the active indication under investigation during its clinical development phase.[2]

The design of ABBV-787 as an ADC incorporating a degrader payload represented a strategic investment in next-generation targeted oncology therapies. ADCs, by their nature, aim to enhance the therapeutic index of potent cytotoxic agents by minimizing systemic exposure and maximizing drug concentration at the tumor site.[4] The utilization of a protein degrader as the payload component is a further refinement of this strategy. Protein degraders, such as those employed in Proteolysis Targeting Chimeras (PROTACs) which share conceptual similarities with the payloads in Degrader-Antibody Conjugates (DACs), are designed to catalytically induce the elimination of target proteins rather than merely inhibiting their function.[4] This approach holds the potential for increased potency, more durable responses, and the ability to overcome resistance mechanisms often associated with traditional inhibitors. Consequently, the combination of ADC-mediated targeting with the novel mechanism of a degrader payload, as seen in ABBV-787, signifies a sophisticated and potentially more efficacious approach to cancer therapy, reflecting a broader industry trend toward