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Interceptor

INTERCEPTOR – targeting brain cancers with WPD401 molecule

WPD401 is an advanced multivalent targeted cytotoxin towards four cancer-associated cell-surface receptors: IL-13Ra2, EPHA2, EPHA3, and EPHB2. The molecule is composed of a multitargeting ligand chemically conjugated to a toxic payload. Upon binding to one of the four receptors, the cytotoxin is internalized via endocytosis where it releases the cytotoxic agent. The released chemical is a potent microtubule disrupting agent which triggers cancer cell apoptosis, destroying a tumor. 

WPD401 was designed to target glioblastoma cells, regardless of their inherent heterogeneity. WPD401 selectively and potently eliminates cancer cells, including glioma stem-like cells, infiltrating cells, neo-vasculature, and immunosuppressive tumor microenvironment. IL-13Ra2, EPHA2, EPHA3, and EPHB2 tumor-associated receptors are conjointly found in nearly every grade IV glioma and constitute very attractive targets for multivalent monotherapy with WPD401. Thus, WPD401 may closely target all cases of glioblastoma. Even when one receptor is not present on a glioma cell, the cell will be still effectively targeted by the cytotoxin. Since the WPD401-targeted receptors may be associated with other tumors, their brain metastases could also potentially be targeted with the cytotoxin. WPD401 is an excellent candidate drug to effectively treat gliomas and other primary and metastatic brain tumors.

We were encouraged by the previous results of a related combination therapy approach with a mixture of two cytotoxins targeting IL-13Ra2 and EPHA2 receptors from preclinical model of spontaneous gliomas in dogs (2021). The treatment resulted in 50% clinically relevant responses. We postulate the introduction of combination therapies to obtain more comprehensive and durable responses.

Future

Our preclinical studies to date have confirmed the effectiveness of targeting the glioblastoma-associated receptors with WPD401 and its potent cytotoxicity. The ongoing transfer of manufacturing technology will advance the cytotoxin to further planned toxicokinetic and future human clinical trials.

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