Griffen Securities Positive on ZIOPHARM's (ZIOP) Latest Membrane-Bound IL-15 Data; Affirms at 'Buy'
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Griffen Securities reaffirms ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) at Buy with a price target of $21 after the company announced the publication of data demonstrating enhanced persistence of genetically modified T cells targeting leukemia through utilization of its non-viral Sleeping Beauty (SB) system to co-express membrane-bound IL-15 (mbIL15) and a CD19-specific chimeric antigen receptor (CAR).
The firm offered the following commentary today:
Membrane-bound IL-15 (mbIL15) provides the key signal to youthful and persistent T cells. Ziopharm worked for more than two years to create T cells that would be able to attack an existing cancer and provide a lasting immune response against disease recurrence. As described in a new publication, the Company selected interleukin-15 (IL-15), a cytokine that increases T-cell persistence, to create a new signal via its collaboration with Intrexon. The approach involved fusing IL-15 to the IL-15 receptor a subunit so the fusion protein would provide a constant stimulus to support T cell persistence even in the absence of a tumor-associated antigen. This strategy was applied to the development of CD19CAR T cells.
The mbIL15 unit favors T memory stem cells (Tscm) formation. These cells are rare, but are extremely attractive for immunotherapies as they are the least differentiated memory T cell and can give rise to cytotoxic T cells. Ziopharm evaluated the mbIL15-CD19CAR T cells and found that they tested positive for the mbIL15 protein and Tscm biomarkers as well as expression of interferon-? and activation upon exposure to antigen-presenting cells. What’s more, the modified T cells remained viable for up to two years in culture without antigen stimulation. Yet, they did not demonstrate aberrant unrestricted proliferation and exhibited a normal karyotype and polyclonal T-cell receptor repertoires. Thus, these cells have the hallmarks of a Tscm.
The mbIL15-CD19CAR T cells displayed impressive in vivo functionality. They’ve shown no host toxicity or evidence of aberrant proliferation after long-term engraftment (125 days after infusion) preclinically. A test performed in a model of minimal residual disease or low tumor-associated antigen demonstrated the mbIL15-CD19CAR T cells rapidly eliminated leukemia cells by day 22, enabling 43% of the animals to survive to day 98. In contrast, 100% of the control mice died by day 34. A final test assessed the cells’ ability to eradicate an established malignancy and prevent disease recurrence. The results showed the mbIL15-CD19CAR T cells engrafted, mounted an antitumor response, and persisted after tumor clearance with no sign of relapse.
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