On November 17, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the presentation of both clinical and nonclinical data for Ad-RTS-hIL-12 + orally-administered veledimex for recurrent brain cancer at the 21st Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) held November 17-20, 2016 in Scottsdale, Arizona (Press release, Ziopharm, NOV 17, 2016, View Source [SID1234516675]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate utilizing the proprietary RheoSwitch Therapeutic System (RTS) technology for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating a vigorous immune response against cancers.

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In a poster presentation titled "Phase 1 study of intra-tumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex is well tolerated and suggests survival benefit in recurrent high-grade glioma," the Company will report interim results from patients with recurrent high-grade gliomas enrolled in three veledimex dosing cohorts (20mg, n=7; 30mg, n=4; and 40mg, n=6). Subjects with relapsed high-grade gliomas, either glioblastoma (GBM) or anaplastic astrocytoma (AA), undergoing re-resection were intra-tumorally injected once with Ad-RTS-hIL-12 along with oral doses of veledimex to activate and control production of IL-12.

As of October 14, 2016, the date of data collection for the SNO presentation, median overall survival (mOS) was 12.8 months, with 11 of 17 subjects alive. Survival rates at 6, 9, and 12 months for patients with multiple recurrences prior to administration of Ad-RTS-hIL-12 are described in the table:

Treatment N Relapsed Brain Tumor Medium #
Recurrences mOS (months) Survival Rate (%)
6 months 9 months 12 months
Ad + V (Overall) 17 16 GBM, 1 AA 3 12.8 87 65 54
Ad + V (20 mg) 7 6 GBM, 1 AA 3 12.8 100 86 71
GBM is an aggressive brain tumor affecting approximately 74,000 people worldwide each year.i,ii For patients who have experienced recurrences the prognosis is particularly poor, with a mOS of 6-7 months, while mOS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iii, iv

In the study, IL-12 leading to the production of interferon-gamma in the bloodstream was measured and found to be proportional to the three doses of veledimex, demonstrating that this orally-delivered activator crossed the blood brain barrier to engage the RTS gene switch and express IL-12 in a dose-dependent manner. Toxicities in all three dose cohorts were consistent with those previously reported, with a higher incidence of grade 3 or greater adverse events in the 40 mg dose group. Importantly, all related side effects were reversed upon cessation of veledimex. Based on the tolerability and survival benefit seen, the 20 mg dose of veledimex has been selected for an ongoing expansion cohort.

"These translational data confirm the activity of Ad-RTS-hIL-12 + veledimex in the clinic, demonstrating that veledimex crosses the blood brain barrier to activate the RheoSwitch gene switch and produce IL-12, resulting in an immune response to the tumor and now, impressively, overall survival outcomes," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "With median overall survival beyond 12 months in these patients who have experienced multiple recurrences, the therapeutic potential of Ad-RTS-hIL-12 + veledimex is very promising. We look forward to enrolling additional patients in the expanded 20 mg dose cohort and to discussing the results of the Phase I multi-center study with the FDA, with the goal of determining a registration pathway for this therapeutic in a disease with far too few treatment options."

The Company will also present results from a pre-clinical study of Ad-RTS-mIL-12 + veledimex as an investigational therapy for pediatric glioma in a poster titled "Local regulated IL-12 expression as an immunotherapy for the treatment of pontine glioma". Glioma in the pontine region of the brain accounts for approximately 15% of all cases of pediatric brain tumors, with a median survival time of less than one year. In an orthotopic pons model, veledimex was shown to cross the blood brain barrier to control mouse IL-12 production from the tumor, which stimulated the immune system and resulted in a profound increase in overall survival. Based on these results, the Company plans to initiate a Phase 1 clinical trial in pediatric brain tumors, including diffuse intrinsic pontine glioma (DIPG) in 2017.

"DIPG is an aggressive disease, and because of its location in the brain, it is virtually untreatable," added Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "Ad-RTS-hIL-12 + veledimex has unique potential in this indication especially given our ability to not only turn IL-12 on and off, but also to titrate IL-12 levels thanks to the RTS technology. Our Ad-RTS-IL-12 + veledimex program continues to gain momentum, with the potential for a registration pathway in recurrent high-grade glioma in adults and expected study initiations as monotherapy in pediatric patients, as well as, in combination with checkpoint inhibitors in adult patients with brain cancer."

All poster presentations will be available online at www.ziopharm.com.