Ziopharm Wages Its Own War on Brain Cancer

When we hear about a new approach that promises bringing in hopefulness in patients diagnosed with brain glioma, we try to listen and hope for the best, rather than develop and demonstrate  skepticism. Are we not walking the road of genetic engineering, gene therapy approaches and immunotherapy? Our optimism becomes realistic, especially when a scientific rationale is explained by researchers in scientifically solid firms that are specialized in cancer treatment with novel breakthrough methods.

As a matter of fact, Ziopharm Oncology (ZIOP), a Boston-based biotechnology company, employs novel gene expression control and cell technologies to deliver safe, effective and scalable cell-based therapies for the treatment of cancer. The Company’s synthetic cancer immunotherapy programs, in collaboration with Intrexon (XON) and the MD Anderson Cancer Center, include chimeric antigen receptor T cell (CAR-T) and other adoptive cell based approaches that use non-viral gene transfer methods for broad scalability.

Ziopharm Oncology, together with Intrexon, are advancing programs in multiple development stages. They are walking the road towards using Intrexon’s RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index. Ziopharm,’s pipeline includes a number of cell-based therapeutic products and approaches in various phases of clinical and preclinical testing, with the aim of treating hematologic and solid cancers.

The Announcement

Today Ziopharm announced that a presentation titled “Intratumoral Regulated Expression of IL-12 as a Gene Therapy Approach to Treatment of Glioma,” will be delivered at 5:15 pm CT, Saturday, November 21, 2015 at the 20th Annual Society for Neuro-Oncology (SNO) Annual Scientific Meeting in San Antonio, Texas.

The presentation includes initial results from an ongoing Phase 1 dose-escalation study of Ad-RTS-hIL-12 + orally administered veledimex in recurrent or progressive glioblastoma or grade 3 malignant glioma.

Ad-RTS-hIL-12 is used with the oral activator veledimex — a novel viral gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T-cell immune response.

Nino Chiocca, MD, PhD, Harvey W. Cushing Professor of Neurosurgery, Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute, Chairman, Neurosurgery, Brigham And Women’s Hospital and Co-Director, Institute for the Neurosciences, Brigham And Women’s Hospital said: “Immunotherapy is an attractive approach for the treatment of glioma, an aggressive cancer with few treatment options. IL-12 is among the most potent anti-cancer immune cytokines, yet carries equally significant potential for immune-mediated toxicities. The ability to turn IL-12 expression on and off using an orally activated gene switch, particularly in the brain’s immune privileged environment, is a tremendous advancement in the potential of this therapeutic approach. We look forward to enrolling additional patients and follow up from this study to evaluate Ad-RTS-IL-12’s potential in this challenging, rapidly advancing and lethal disease.”

The ongoing multi-center Phase 1 trial of Ad-RTS-hIL-12 + veledimex examines a gene therapy strategy for recurrent high grade gliomas, with the goal of generating a localized anti-tumor immune response.

The primary objective of the study is to determine the safety and tolerability of a single intra-tumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 + veledimex maximum tolerated doses, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response. The study is expected to enroll up to 72 subjects.

Important to learn that the effects of Ad-RTS-mIL-12 + veledimex were studied in orthotopic glioma animal glioma mouse model that evaluated dexamethasone, bevacizumab, temozolamide and a PD-1 inhibitor. Ad-RTS-mIL-12 + veledimex demonstrated a dramatic dose-related increase in survival, without significant adverse events, that was superior to all other treatments.

Some hinted observations

In the current, ongoing Phase 1 study, five patients are available for initial assessment, two with recurrent grade 3 malignant gliomas and three with grade IV.

Results: IL-12 was detectable in peripheral blood along with downstream IFNg, which indicates that veledimex crossed the blood brain barrier activating IL-12 expression from intra-tumor administered Ad-RTS-hIL-12. Ad-RTS-hIL-12 + veledimex was well tolerated with minimal neurologic toxicity.

The most common adverse events were headache, fever, hyponatremia and nausea/vomiting. Related serious adverse events were aseptic meningitis, neutropenia, thrombocytopenia, leukopenia, with all toxicity to date consistent with the “on-target” effects of immunotherapy.

Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm said, “Observing that veledimex can cross the blood brain barrier and that IL-12 expression can be regulated in the brain, demonstrates a clear translation of results from the laboratory to the clinic. We look forward to follow-up of the current recipients and to further enrollment in this multi-center gene therapy study.”

Prohost Comments

It will be interesting to hear Ziopharm’s presentation at the 20th Annual Society for Neuro-Oncology (SNO) Annual Scientific Meeting in San Antonio, Texas. We are all ears and full of optimism regarding the evolution in cancer treatment through genetic engineering and immunotherapy. Our optimism, however, will not interfere with the market frequent traders’ loyalty to their rule of thumb, dictating that they must sell stocks announcing good news, a law that has become a tradition called “Sell Good News”.

While market traders are busy selling good news, we are going to hear what the real scientists are going to tell us. We wish we could bring back with us some hope for glioma patients who have nothing  to hope for except positive news about investigational drugs and approaches in the pipelines of some small in size, but big in science, biotech firms.

We are optimistic.

Other small biotech firms pursuing the same goal see Celldex (CLDX)and Agenus (AGEN).

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