On July 22, 2014 ZIOPHARM Oncology reported the expansion of synthetic immuno-oncology programs in conjunction with Intrexon to include chimeric antigen receptor T-cell (CAR-T) therapy (Press release Intrexon, JUL 22, 2014, View Source;p=RssLanding&cat=news&id=1949640 [SID:1234500637]). Additionally the Company has provided an update on its development efforts with the proprietary RheoSwitch Therapeutic System (RTS) platform, an inducible regulator for expression of therapeutic molecules through administration of an oral activator ligand, as well as its clinical program with Ad-RTS-IL-12, a novel DNA-based therapeutic candidate for the controlled expression of IL-12.
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CAR-T cells represent an emerging, high value immunological therapy that can target and destroy cancer cells displaying "personalized" fingerprints, yet current approaches feature challenges associated with toxicity, off-target effects, and uneconomical manufacturing. Intrexon possesses the integrated technology platforms, molecular engineering, systems biology, and cell engineering capabilities required to overcome these challenges and fully realize the potential of CAR‐T cell therapies. Most significantly, utilization of the RTS platform will facilitate exquisite regulation of one or more bioeffectors in CAR-T cells enabling physicians to control systemic effects of cell therapies with an appropriate dosing regimen of the oral activator ligand (veledimex), and eventually bring about improved safety and efficacy of these and related therapeutic strategies. Further preclinical work is underway in this promising area of study, and ZIOPHARM and Intrexon expect to provide a progress update in the second half of 2014.
Samuel Broder, M.D., EVP of Scientific and Public Affairs at Intrexon, said, "As a leader in the second generation of biotechnology, Intrexon is applying industrial engineering principles to synthetic immunology to potentiate important biotechnology platforms enabling end-to-end solutions for complex biologic challenges. In particular, the utilization of our proprietary RheoSwitch platform may be especially advantageous in CAR-T treatments."
To date, the RheoSwitch platform has been shown to function as a regulatable switch in an array of cell types for multiple proteins, and RTS expansion into CAR-T therapy is further demonstration of the breadth of Intrexon’s single and multi-genic expression and control technologies. According to data from ClinicalTrials.gov, more than 1,000 clinical trials utilizing gene therapy are currently underway, with the majority in either Phase I or Phase II. Intrexon’s proprietary switch system is uniquely positioned as the first clinically-evaluated gene switch with in vivo data showing the ability to control gene expression with a broad dynamic range. The RTS platform provides a mechanism for titrating therapeutic effects on a patient-specific and predictable basis, as well as a safety switch to rapidly turn off gene-expression. The ability to administer or withdraw the veledimex pill to sustain continued treatment cycles is a key benefit exclusive to RTS technology.
"We are excited by the prospects of applying our advanced synthetic immuno-oncology toolkit towards targeted immunotherapies like CAR-T," said Jonathan Lewis, M.D., Ph.D., CEO of ZIOPHARM. "We also look forward to expanding RTS applications in novel therapeutic strategies for cancer where the ability to control gene expression is essential."
With respect to the Ad-RTS-IL-12 clinical programs, ZIOPHARM continues to conduct Phase II studies in melanoma and breast cancer using Ad-RTS-IL-12 as a monotherapy. Additionally, the Company is evaluating future trials with IL-12 in potential combination therapies with other immune-targeting agents in various cancers including melanoma and breast. ZIOPHARM also plans to initiate a Phase I trial to evaluate Ad-RTS-IL-12 as a single agent in the treatment of patients with Glioblastoma Multiforme in the second half of 2014.
"The development of potent yet tightly controlled cancer depleting therapies such as CAR-T and other targeted cellular products through the molecular rewiring of immunologic gene programs adds to the foundation of our multifaceted strategy in synthetic immuno-oncology," remarked Gregory Frost, Ph.D., SVP of Intrexon’s Health Sector.