Z-007 / Zola Therapeutics - LARVOL DELTA

Preclinical characterization of a first-in-class RNA/DNA hybrid TLR7/8/9 agonist, Z-007, ex vivo in human tumor-associated cells, in vivo in mice and primates, and tumor regression in mice. (SITC 2025) - "Recently, vidutolimod, the first CpG-A TLR9 agonist, showed systemic monotherapy activity (9/40 responses) in PD-1 blockade-resistant melanoma.1 In the randomized ECOG-ACRIN EA6194 trial in neoadjuvant melanoma, the addition of vidutolimod induced a 20% increase in pathologic complete response compared to pembrolizumab alone, supporting earlier data in a non-randomized trial.2 3 Vidutolimod is delivered in a viral-like particle that induces neutralizing antibodies,4 5 and vidutolimod resistance in advanced melanoma is associated with TLR7/8+, TLR9- immune suppressive tumor-associated myeloid cells (TAM).6 We hypothesized that co-stimulating TLR7/8/9 with an RNA/DNA mimic of viral replicative complexes in a non-immunogenic LNP may activate TAM and overcome vidutolimod resistance, inducing more effective anti-tumor responses.Methods We designed and synthesized novel native backbone RNA/DNA hybrids to co-stimulate TLR7/8/9. For pharmacodynamics comparison, the corresponding..."

Preclinical • Melanoma • Oncology • Peritoneal Cancer • Solid Tumor • CD8 • CXCL10 • IFNA1