ZIOPHARM Offers Promising Nonclinical and Phase I Study Results of Ad-RTS-IL-12 in Advanced Melanoma at ASGCT 16th Annual Meeting

ZIOPHARM Oncology, Inc.

today announced promising results from nonclinical and Phase 1 studies in advanced melanoma using Ad-RTS-IL-12, a novel DNA-based therapeutic candidate. Findings were presented in an oral session at the 16^th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), held May 15-18 in Salt Lake City, Utah. A presentation of the study, titled "Nonclinical and Phase I Clinical Studies with a Regulated Adenoviral Gene Delivery of IL-12 Show Promising Clinical Activity in Unresectable Stage III/IV Melanoma," was delivered by John Nemunaitis, M.D., Executive Medical Director of Mary Crowley Medical Research Center. For the studies, Ad-RTS-IL-12, utilizing RheoSwitch Therapeutic System® (RTS®) technology, was injected intratumorally. Gene expression and protein production were controlled through the administration of an oral activator ligand (INXN-1001). Nonclinical studies demonstrated a dose-dependent, immune mediated reduction in tumor volume in several different syngeneic tumor models, which led to a Phase 1 dose-escalation study in subjects with unresectable stage III/IV melanoma. Study subjects (n=14) were treated in four dose cohorts of the activator ligand. Compelling clinical activity was observed in five of seven (71 percent) patients dosed at the two highest dose levels. These five patients experienced prominent inflammatory responses in injected and non-injected lesions and transient increases then decreases in the size of injected and non-injected lesions. Clinical activity in these higher dose cohorts coincided with the highest serum levels of IL-12 and IFN-γ, including a four-fold median increase from baseline at peak levels compared with lower dose cohorts. Flow cytometric analyses of peripheral blood mononuclear cell (PBMC) samples also revealed seven-fold and four-fold median increases from baseline at peak levels in absolute CD3+ and CD8+ T cell values, respectively, compared with lower dose cohorts. The most common related adverse events (AEs) included fever, nausea, vomiting, fatigue and arthralgia. One death occurred in the study, unrelated to treatment, due to septicemia secondary to cellulitis and colitis.