Our work is centered on developing a treatment for adult and pediatric brain cancers so patients have a durable treatment option.
The cytokine IL13 interacts with the ubiquitous IL13 receptor alpha 1 (IL13Rα1) to activate cell death-inducing pathways. Cancer cells mask these actions by upregulating the IL13 Receptor alpha 2 (IL13Rα2). As such, IL13Rα2 represents a tumor-specific target for novel therapies.
Data from the Phase 3 trial of the non-selective IL13 receptor toxin, Cintredekin Besudotox, for brain cancer indicated that patients were experiencing off-target toxicity that significantly limited the ability for that drug to work. We knew we needed to reach higher specificity with a better-targeted drug.
GB13 is an IL13-based immunotoxin that specifically binds IL13Rα2 on cancer cells and induces cell death via Pseudomonas exotoxin A-mediated activity.
Research & Development
GB-13 contains an amino acid mutation in the IL13 domain that blocks binding to IL13Rα1 on non-cancerous cells and promotes high affinity IL13Rα2-specific engagement with cancer cells. This translates to a selective immunotoxin without non-specific targeting toxicities that is effective at nM concentrations.
Our pre-clinical activities have focused on adult glioblastoma and pediatric midline gliomas, which have not seen significant therapeutic advancements for decades. The majority of these patients' tumors express the cancer associated receptor and tumors are amenable to catheter-based convection enhanced delivery.
Over 70% of adult glioblastomas (GBM) and pediatric diffuse midline glioma (DMG) express IL13Rα2, representing a highly prevalent target.
We are designing a focused trial that will carefully evaluate the tumors to be treated in both adult glioblastoma and pediatric diffuse midline gliomas with GB-13.
In our clinical trials, we will first test tumors and enroll patients based on IL13Rɑ2 positivity to provide the greatest chance for successful treatment. GB-13 will then be administered via CED into the tumor. Tumors will subsequently be removed to ascertain the exact efficacy of GB-13. This process will allow us to refine dosing and treatment duration to optimize our clinical protocols going forward.