Tocagen: Preclinical data on 511 & Toca FC published in Neuro-Oncology
Tocagen announced the publication of preclinical data in Neuro-Oncology from two independent research programs which together detail proposed mechanisms of action for Toca 511 & Toca FC involving direct tumor killing and activation of the immune system against cancer cells. The papers were published in the July issue of Neuro-Oncology, which appeared in print on June 16, and were featured on the cover and highlighted in an editorial. The articles first appeared online on April 6. In the article titled, "Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable anti-tumor immunity in a mouse glioma model," Mitchell, et al., monitored and characterized immune cell populations in the tumor microenvironment in mouse models of brain cancer over the course of treatment with Toca 511 and 5-FC, the active component of the Toca FC tablets used in humans. Results showed treatment-induced loss of immune cell subsets that have been shown to contribute to the suppression of normal immune activity against cancer cells, including reduction of tumor associated macrophages, myeloid-derived suppressor cells and tumor associated monocytes. Depletion of immune-suppressive myeloid cells was followed by increases in CD4+ and CD8+ T cells which correlated with tumor reduction. Mice that cleared tumors following treatment with Toca 511 and 5-FC were protected against re-challenge with the same tumor type. Furthermore, successful adoptive cell transfer experiments using isolated immune cells from successfully treated animals confirmed anti-tumor immune responses were T cell-dependent. In the article titled, "Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anti-cancer immunity," Hiraoka and Inagaki, et al., performed molecular imaging of immune-deficient and immune-competent mouse models of brain cancer following treatment with Toca 511 and cycles of 5-FC. These studies were performed in the laboratory of Noriyuki Kasahara, M.D., Ph.D., professor of cell biology and pathology at the University of Miami. While long-term survival benefit was seen in both models, tumor was undetectable in immune-competent mice after three cycles of 5-FC. In contrast, immune-deficient mice required continuous treatment with cycles of 5-FC for long-term survival benefit, and tumor recurrence was still evident between cycles. After clearance of tumors in immune-competent mice by treatment with Toca 511 and 5-FC, long-term protection against future challenge with the same tumor type was seen. Long-term immune memory against the tumor was lost upon depletion of T cell subsets, indicating a T cell-dependent anti-tumor immune response. The complementary findings reported in these publications demonstrate that anti-tumor immune effects are T-cell dependent and correlate with depletion of immune-suppressive myeloid cells. Toca 511 & Toca FC is in clinical development for the treatment of recurrent high grade glioma, or HGG, a type of brain cancer. Tocagen has completed enrollment of the Phase 2 portion of a Phase 2/3 clinical trial and plans to report top-line results of the study in the first half of 2018. The U.S. FDA granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of patients with recurrent HGG.