Z-007 / Zola Therapeutics - LARVOL DELTA

Reprogramming tumor-associated immune cells with Z-007, a first-in-class systemic TLR7/8/9 agonist. (ASCO 2026) - "Z-007 represents a novel class of innate immune activator that successfully decouples high IFN-a induction from pro-tumorigenic inflammation. Its ability to reprogram human MDSCs and induce tumor regression in multiple murine models and in spontaneous canine tumors without evidence of CRS, fever, or altered liver, kidney, or other organ function, supports its clinical development. Based on the propensity of LNPs to be taken up in the liver, IV Z-007 may reprogram tumor-associated immune cells in patients with liver metastases from a wound healing to antiviral response, inducing systemic anti-tumor CD8+ T cell responses."

Immune cell • Angiosarcoma • Gastrointestinal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • CD8 • CXCL10 • IFNA1 • IFNG • IL6 • TLR9 • TNFA

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