DDEL-16. DELIVERY OF OT-101 - TGF-Β ANTISENSE- FOR THE TREATMENT OF GLIOBLASTOMA

Abstract OT-101 - a TGF-beta antisense- is active against recurrent glioblastoma in G004- phase 2 clinical trial [Uckun FM, Qazi S, Hwang L, Trieu VN. Recurrent or refractory high grade gliomas treated by convection enhanced delivery of TGF-beta2 targeting RNA therapeutic: post-hoc analysis with long-term follow up. Cancers. 2019, 11:1892]. was delivered intratumorally Convection Enhanced Delivery (CED). To further expand the application OT-101, we explored intrathecal tritiated into Sprague-Dawley CD (albino) rats. Throughout studies, there were no sex differences. After 1 hr intracerebral infusion rats, limited to site. Whereas for itravesicular infusion, more widespread 35X, 19X, 12X higher concentration found cerebellum, remaining cerebrum, cerebrospinal fluid (CSF), respectively. stable first 4 hours post and decayed biexponentially slow terminal half life tissue but not CSF, suggestive rapid penetration underlying away from CSF compartment. Minimum amount detected plasma Intrathecal bolus administration 0.1mL at 14, 30, 200, 300, 500 uM cynomolgus monkies did result any single dose toxicity. Histopathology examination revealed substance-related histomorphological lesions cavum subarachnoideale lumbar region. No changes noted grey white matter spinal cord, nerve trunk, cells show abnormalities. These data suggest that potentially effective route antisense therapeutics such as midline ie. Diffuse Midline Glioma (DMG). A 1b/2 evaluating DMG proposed design will be presented