2B3-101 (glutathione PEGylated liposomal doxorubicin) is being developed for patients suffering from multiple brain cancer indications, with an initial focus on patients with brain metastases of breast cancer and patients with glioma. 2B3-101 is based on the existing chemotherapeutic agent doxorubicin and has completed a Phase I/IIa clinical trial for various forms of brain cancer.

Medical need and existing therapies

Each year, approximately 400,000 patients across the globe are affected by primary and secondary brain tumors. Treatment options are limited and overall prognoses is poor. The neuroprotective blood-brain barrier limits the delivery of many anti-cancer drugs to tumors in the brain, especially to micrometastases and invasively growing tumor sprouts which are still behind an intact blood-brain barrier.

Doxorubicin is a conventional anthracycline that, either formulated as free drug or encapsulated in (PEGylated) liposomes, is a widely used chemotherapeutic anticancer treatment. In these formulations, however, doxorubicin does not readily cross the blood-brain barrier within a therapeutic window to effectively treat tumors in the brain.

Benefits of 2B3-101

2-BBB has developed 2B3-101 by applying the G-Technology® to the already marketed PEGylated liposomal doxorubicin formulations (Doxil®/Caelyx®), by conjugating the brain-targeting ligand glutathione to the tips of the PEG. 2-BBB has been able to show therapeutic benefit and predictable safety profile of 2B3-101 in pharmacological and non-clinical safety studies. In preclinical proof-of-concept studies in a human glioblastoma cell xenograft model, 2B3-101 treatment resulted in significant inhibition of brain tumor growth while non-targeted PEGylated liposomal doxorubicin and free doxorubicin at the same dose was completely ineffective. Compared to non-targeted PEGylated liposomal doxorubicin, 2B3-101 had an optimal distribution to the brain. (PLOS One, January 2014; Journal of Pharmaceutical Sciences, April 2014)