zabilugene almadenorepvec + topotecan

VCN-01 + topotecan is an investigational combination therapy consisting of zabilugene almadenorepvec (VCN-01), a first-in-class, stroma-degrading oncolytic adenovirus, and topotecan, a small-molecule topoisomerase I inhibitor chemotherapy. VCN-01 is genetically engineered to selectively replicate in tumor cells with a dysfunctional retinoblastoma (pRB) pathway (characterized by high levels of free E2F-1 transcription factor) and to express human PH20 hyaluronidase, which degrades hyaluronic acid in the tumor extracellular matrix to facilitate viral spread and chemotherapy penetration. Topotecan acts as a topoisomerase I inhibitor, inducing S-phase arrest and upregulating E2F-1, which synergistically enhances VCN-01 infection, replication, and oncolytic activity. Developed by Theriva Biologics (formerly Synthetic Biologics) and its subsidiary VCN Biosciences, this combination is being evaluated for the treatment of refractory or resistant intraocular retinoblastoma with vitreous seeds.