Clinical efficacy of the antitumor agent ONC201 in GBM

DESCRIPTION provided by applicant ONC is a clinical stage first in class small molecule with demonstrated anticancer activity against aggressive refractory recurrent glioblastoma multiforme GBM tumors in vitro ex vivo and in vivo This novel compound imparts its antitumor effects through a unique mechanism of action that involves indirect dual inactivation of Akt and ERK in tumor but not normal cells Several academic investigators at premier institutions have demonstrated the optimal preclinical profile of ONC in a multitude of models These findings have prompted Oncoceutics to rapidly translate this product into the clinic to treat advanced cancer patients The first in man trial is a phase I II study that will include patients with GBM is scheduled to begin in early at MGH and has been reviewed by the FDA as part of the accepted IND Following completion of the dose escalation phase I portion of the trial supported by Oncoceutics the phase II trial can begin to evaluate the monoagent efficacy of ONC in patients with advanced GBM In this fast track application we propose to develop an automated manufacturing process to provide the clinical supply of drug product followed by evaluation of the clinical efficacy of the resulting product in patients with GBM Phase Aim Optimize ONC formulation and produce GMP product for GBM trial Phase Aim Evaluate clinical efficacy of oral ONC in GBM These studies will enable a development path for ONC to treat GBM which is otherwise unattainable based on investor feedback that indicates a clear need for pilot clinical data in the indication to enable private support This proposal seeks to make a novel anticancer agent available to patients in dire need of treatment options will push the product toward commercialization sufficiently derisk private investments to enable subsequent development and will advance the field forward by enabling clinical evaluation of a novel therapeutic mechanism PUBLIC HEALTH RELEVANCE This proposal seeks to develop a new cancer drug called ONC for patients that have a deadly aggressive brain tumor that does not respond to any available treatments ONC works very effectively in brain tumor cell models in laboratories does not have toxic side effects in animals at doses that shrink tumors and works by in a way that has never been discovered before The FDA recently gave their permission for ONC to be tested in humans for the first time The first part of this proposal will develop a manufacturin process that will produce drug for use in human studies The second part of this proposal will evaluate the ability of ONC to shrink brain tumors in a small number of patients If the drug works in this trial investors would be willing to support further develop of the drug so that it cn be approved to treat cancer in the US and eventually around the world