SGN-BB228: An Investigational Bispecific Antibody-Anticalin Fusion for Advanced Solid Tumors

1. Executive Summary

SGN-BB228, also identified as PF-08046049 and formerly PRS-346, is an investigational immuno-oncology agent demonstrating a novel approach to cancer therapy. It is a bispecific antibody-Anticalin fusion protein engineered to dually target CD228 (melanotransferrin) expressed on tumor cells and the 4-1BB (CD137) costimulatory receptor on immune cells. This mechanism is designed to create a conditional activation of 4-1BB signaling, primarily localized within the tumor microenvironment, thereby enhancing T-cell-mediated anti-tumor cytotoxicity while potentially mitigating the systemic toxicities observed with previous 4-1BB agonists.

The development of SGN-BB228 originated from a collaboration between Pieris Pharmaceuticals, which contributed its proprietary Anticalin® technology, and Seagen Inc., which advanced the molecule into clinical trials. Following Pfizer's acquisition of Seagen, SGN-BB228 has become part of Pfizer's extensive oncology pipeline. Currently, SGN-BB228 is undergoing a multi-part Phase 1 clinical trial (NCT05571839) to evaluate its safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity in patients with advanced melanoma and other solid tumors, including non-small cell lung cancer, colorectal cancer, pancreatic cancer, and mesothelioma. Preclinical evidence supports its targeted mechanism and potential efficacy, particularly in models of checkpoint inhibitor resistance. The strategic acquisition by Pfizer underscores the perceived potential of assets like SGN-BB228 and the broader technological platforms they represent. The core promise of SGN-BB228 lies in its potential to offer a more targeted and tolerable approach to 4-1BB agonism, a pathway with significant, yet historically challenging, therapeutic potential in oncology.