On January 9, 2018 Ziopharm Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company developing gene- and cell-based immunotherapies for cancer, today reported an update on the Company’s clinical programs and corporate development activities during the 36th Annual J.P. Morgan Healthcare Conference (Press release, Ziopharm, JAN 9, 2018, View Source [SID1234523033]).
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"Ziopharm’s immunotherapies in clinical trials are based on two powerful platforms. First, we have shown that we can super-charge a patient’s own immune system with controlled, local production of IL-12 and second, we can provide a new immune response where none existed, infusing genetically modified T cells with a unique and advantageous manufacturing process," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm. "Producing IL-12 in the tumor microenvironment under full control is a new drug platform for oncology, which we will further exploit by combining with checkpoint inhibitors. Likewise, we are implementing a new paradigm for production of genetically modified T cells with our Sleeping Beauty (SB) non-viral platform and proprietary membrane bound IL-15 which enables very rapid manufacture of CAR- and TCR-modified cells at low cost and scale."
The Company’s corporate presentation at the J.P. Morgan conference is Thursday, Jan. 11, at 10 a.m. PST. To access a live audio webcast of the presentation, please visit the Investor Relations section at www.ziopharm.com. The webcast will be archived for 90 days.
Program Updates
Controlled IL-12 for Gliomas
Ziopharm, in partnership with Intrexon Corporation (NYSE:XON), is advancing Ad-RTS-hIL-12 plus veledimex, or controlled interleukin-12 (IL-12), as a gene therapy for recurrent glioblastoma (rGBM). Ad-RTS-hIL-12 is an adenoviral vector administered via a single injection into the brain tumor and engineered to conditionally express human interleukin-12 (hIL-12). The expression of hIL-12 is modulated with the RheoSwitch Therapeutic System (RTS) by the small molecule veledimex, an activator ligand which has been shown to cross the blood-brain barrier. A Phase 1 trial produced compelling data demonstrating the safety of controlled local expression of IL-12 and that IL-12 can turn previously cold tumors hot, which could have a profound impact for oncology in general.
Combination Trial with OPDIVO (nivolumab) Initiated – The Company announced the initiation of a Phase I clinical trial to evaluate Ad-RTS-hIL-12 plus veledimex in combination with OPDIVO (nivolumab), an immune checkpoint, or PD-1, inhibitor, in adult patients with rGBM.
Pivotal Trial to Initiate in Second Half of 2018 – The Company updated guidance on its planned pivotal trial and announced that it will initiate in the second half of 2018. Ziopharm has designed the randomized control trial to evaluate controlled IL-12 for the treatment of patients with rGBM and following meetings with U.S. and European regulators is completing Chemistry Manufacturing and Control (CMC) technical requirements. The Company continues to engage in partnership discussions in this indication and this updated timeframe allows for accumulation of additional clinical data from the open Phase 1 trials, including the combination trial.
"As the Phase 1 survival data matured over the latter half of 2017, we saw compelling evidence from biopsies, taken more than four months after administration of Ad-hIL-12 plus veledimex, demonstrating that controlled IL-12 causes an influx of killer T cells into brain tumors, and upregulated expression of PD-1 biomarkers," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at Ziopharm. "The randomized control trial will allow us to confirm the activity of our drug as a monotherapy and combining with nivolumab allows us to advance a much needed therapeutic option by exploring a potentially synergistic mechanism of action."
Adoptive Cell Therapies
Ziopharm is developing chimeric antigen receptor (CAR) T cell (CAR+ T) and T-cell receptor (TCR) T cell (TCR+ T) therapies. These programs are being advanced in collaboration with Intrexon and selectively with MD Anderson Cancer Center, the National Cancer Institute (NCI) and Merck KGaA, Darmstadt, Germany.
Initiation of First point-of-care (P-O-C) Clinical Trial Expected in 2018. The Company is advancing its non-viral Sleeping Beauty (SB) platform towards P-O-C for the very rapid manufacturing of genetically modified CAR+ T cells, with the first clinical trial utilizing this approach expected to begin in 2018. Data supporting P-O-C were presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2017, where first- and second-generation SB clinical trial data demonstrated safety, tolerability, disease response including long-term survival, and sustained persistence of infused CD19-specific CAR+ T cells. The Company expects to initiate the third-generation P-O-C study, which leverages SB to manufacture CAR+ T cells co-expressing a membrane-bound interleukin-15, or mbIL15, in less than two days. Manufacturing under P-O-C has the potential to reduce the costs of T-cell therapy and broaden application based on avoiding the need for centralized manufacturing.
Phase 1 Trial of SB-Modified TCRs to Treat Solid Tumors to Initiate in Second Half of 2018. The Company updated guidance on the anticipated start of the National Cancer Institute (NCI)-led Phase 1 trial to evaluate adoptive cell transfer (ACT)-based immunotherapies genetically modified using the SB transposon/transposase system to express TCRs for the treatment of solid tumors. Ziopharm, Intrexon, and the NCI last year entered into a Cooperative Research and Development Agreement to develop and evaluate ACT for patients with advanced cancers using autologous peripheral blood lymphocytes genetically modified using the non-viral SB system to express TCRs that recognize specific immunogenic mutations, or neoantigens, expressed within a patient’s cancer.
"We have used the Sleeping Beauty platform to generate neoantigen-specific T cells and look forward to initiating a clinical trial infusing these genetically modified T cells to target solid tumors," said Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI’s Center for Cancer Research, who is leading this research. "The Sleeping Beauty system is able to target the unique mutations that give rise to a patient’s malignancy."
Phase 1 Trial of CD33-specific CAR+ T Therapy for Acute Myeloid Leukemia (AML). Enrollment is underway in the Phase 1 adoptive cellular therapy clinical trial of CD33-specific CAR+ T cell therapy in patients with refractory/recurrent AML. This study infuses autologous T cells genetically modified with lentivirus to express a CD33-specific CAR and a cetuximab-activated (HER1t) kill switch for elimination of genetically modified cells in the case of unmanageable severe adverse events. The trial is enrolling at The University of Texas MD Anderson Cancer Center. The data are expected to serve as the basis for evaluating CD33 as a potential target for further development using very rapid non-viral manufacturing of T cells under P-O-C.