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Aug. 14, 2019, 3:25 p.m. EDT

Ziopharm Oncology Announces Publication of Positive Results of Phase 1 Monotherapy Trial of Controlled IL-12 in Patients with Recurrent Glioblastoma in Science Translational Medicine

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BOSTON, Aug 14, 2019 (GLOBE NEWSWIRE via COMTEX) -- - Ad-RTS-hIL-12 plus 20 mg veledimex (Controlled IL-12 platform) determined to be the preferred dose

with low-dose steroids to treat adult patients with recurrent glioblastoma -

- Median overall survival for Controlled IL-12 in patients receiving low-dose steroids was 17.8 months -

- Increased tumor infiltrating lymphocytes and PD-1 (programmed cell death protein 1) support

immunological anti-tumor effect of Controlled IL-12 -

Ziopharm Oncology, Inc. ("Ziopharm" or the "Company") /zigman2/quotes/200291745/composite ZIOP -3.58% , today announced the publication of its phase 1 trial of Controlled IL-12 in patients with recurrent glioma in the journal Science Translational Medicine. The publication entitled, "Regulatable interleukin 12 gene therapy in patients with recurrent high-grade glioma: results of a phase 1 trial" can be accessed at https://stm.sciencemag.org/ .

While IL-12 is known as a potent immune activator that triggers T cells to target cancer, historic trials systemically infusing IL-12 protein have failed due to intolerable toxicity. In contrast, this study showed that a ligand-inducible gene switch regulates expression of IL-12 from the central nervous system, resulting in increased cytokine and T-cell activity within the tumor environment, while preserving a favorable safety profile.

Glioblastoma is an aggressive, largely incurable cancer. Patients receive surgery, radiation and chemotherapy, but in almost all cases, tumors return within months. When this brain cancer recurs, median overall survival is six to nine months.

The paper includes data from 31 patients with recurrent glioblastoma (rGBM) treated with Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex, Ad+V). Frequency and severity of adverse events, including cytokine release syndrome, correlated with the veledimex (ligand) dose, reversing promptly upon discontinuation. The 20 mg veledimex dose had superior drug compliance and demonstrated 12.7 months median overall survival (mOS) at a mean follow-up of 13.1 months. Concurrent corticosteroids negatively impacted survival and patients had further improved mOS of 17.8 months when cumulative amount of dexamethasone was limited to less than 20mg during active veledimex dosing.

"I would like to thank the site teams and investigators, as well as all of the patients who participated in this trial," said Laurence Cooper, M.D., Ph.D., CEO of Ziopharm, "This study demonstrated that our Controlled IL-12 platform as monotherapy provides rapid activation of the immune system and is associated with improved overall survival for patients with rGBM, with a favorable safety profile. In addition, the upregulation of PD-1 expression seen upon repeat biopsies in this study supports the decision to pursue our ongoing trials combining Controlled IL-12 with inhibitors to programmed death-1 (PD-1)."

"In a phase 1 trial, we strive to show that a new drug candidate is first and foremost safe for patients and at the same time, aim to demonstrate initial evidence of efficacy," said corresponding author Antonio Chiocca, M.D., Ph.D., lead author and Chairman of Neurosurgery and Co-Director of the Institute for the Neurosciences at Brigham and Women's Hospital, Professor of Neurosurgery at Harvard Medical School, and Surgical Director of the Center for Neuro-oncology at Dana-Farber Cancer Institute. "We believe these study results show it is now possible to have regulatable immunotherapy via genes. Controlled IL-12 is well-tolerated in patients with glioblastoma, with encouraging evidence that the drug is having its intended effect."

"Glioblastoma at recurrence is a devastating cancer with few treatment options that have demonstrated success. These updated data show a promising extension of patients' survival and demonstrate how controlling the powerful cytokine IL-12 can engage the body's own immune system to generate an anti-tumor response against rGBM," said co-author Rimas V. Lukas, M.D., Associate Professor of Neurology (Neuro-Oncology), Northwestern University Feinberg School of Medicine and Department of Neurology, University of Chicago.

About Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex)

Ziopharm's Controlled IL-12 platform is an investigational gene therapy designed to induce and control the production of human interleukin 12 (hIL-12) a master-regulator of the immune system. The Company has treated more than 100 patients, including more than 75 patients with rGBM, with Ad-RTS-hIL-12 plus veledimex and administered more than 1,300 doses of veledimex across three types of solid tumors, building a significant safety profile, mechanistic dataset and evidence of anti-tumor effects.

The Company announced earlier this year the completion of the enrollment in an "Expansion Substudy" (Clinicaltrials.gov NCT03679754) that enlarged the phase 1 trial by an additional 36 patients with Ad-RTS-hIL-12 plus 20mg/day veledimex for up to 14 days. In that cohort, 75% of patients (27/36) received low-dose steroids.

About Controlled IL-12 in combination with PD-1 inhibitors

Ziopharm is also advancing Ad-RTS-hIL-12 plus veledimex for the treatment of rGBM in combination with immune checkpoint inhibitors. In June 2019, the Company announced it had completed enrollment in three dosing cohorts in a phase 1 study of adult patients with rGBM to evaluate a single dose of Ad-RTS-hIL-12 plus daily veledimex in combination with OPDIVO (nivolumab), an immune checkpoint inhibitor against PD-1 (Clinicaltrials.gov NCT03636477). Based on a favorable safety profile, investigators from this multi-center trial indicated interest in expanding the study and the Company now expects to enroll up to 12 additional patients at the highest dosing level.

The Company announced in June 2019 the initiation of a phase 2 trial evaluating the combination of Ad-RTS-hIL-12 plus veledimex with PD-1 antibody Libtayo (cemiplimab - rwlc) for the treatment of recurrent or progressive glioblastoma (rGBM) in adults. The multi-center trial will be conducted at approximately 10 hospitals specializing in the treatment of brain cancers in the United States. The open-label, single-arm phase 2 trial will enroll approximately 30 patients with rGBM, with the primary endpoints being safety and efficacy.

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