rhenium (186Re) obisbemeda
rhenium (186Re) obisbemeda is our lead drug candidate designed for the treatment of recurrent glioblastoma (GBM), leptomeningeal metastases (LM), and pediatric brain cancers (PBCs), such as ependymoma and high-grade glioma.
In preclinical and clinical trials of rhenium (186Re) obisbemeda for treating GBM, ReSPECT-GBM, we delivered up to 20x the absorbed dose of radiation versus standard external beam radiation therapy (EBRT), successfully reducing tumors without significant toxicity. In a preclinical trial of rhenium (186Re) obisbemeda for treating LM, ReSPECT-LM, we administered highly elevated doses of rhenium (186Re) obisbemeda with no maximum tolerable dose reached.
Our novel approach involves drug loading using a specially developed small molecule known as BMEDA with the radioisotope, Rhenium-186, and carrying it into the interior of a nanoliposome where it is irreversibly trapped.
Upon administration, Rhenium-186 emits beta energy that precisely targets rapidly dividing cancer cells, sparing the surrounding healthy cells and tissue, as well as gamma energy that allows us to live image the full treatment infusion.
GBM (Grade IV astrocytoma) is the deadliest and most common type of brain cancer in adults with no treatment options for significantly extending life. PBC is the second most common type of cancer in children and requires less invasive approaches than those for adult patients.
While radiation is highly toxic to cancer, even at an advanced stage, it is difficult to deliver it past the blood-brain barrier and safely into tumor tissue with precision.
In brain cancer, we use convention enhanced delivery (CED), a local drug delivery technique that when paired with nanoliposomal technology, allows us to bypass the blood-brain barrier and directly infuse rhenium (186Re) obisbemeda into the target region.
Catheter Placement
One or more catheters are placed into the brain and then ‘convected’ directly to the tumor. CED uses a hydraulic pressure gradient to drive flow of rhenium (186Re) obisbemeda into a tissue compartment in, around and through the tumor.
Tumor Penetration & Retention
Nanoliposomes of approximately 100 nanometers, such as those used in rhenium (186Re) obisbemeda, have been shown to convect readily and precisely through tumors in the brain.
LM occurs when cancer spreads to the fluid space of the CNS. There are no good treatments in generally recognized standards of care, with patients often having to choose between toxic treatments and a very short life expectancy.
Treatment of LM with external beam radiation must travel through and therefore harm surrounding normal tissues to get to the tumors. Other radiotherapeutics typically cannot reach and destroy the tumor through systemic administration because of the blood-brain barrier.
We take a highly targeted approach, using an Ommaya ventricular reservoir, to directly administer rhenium (186Re) obisbemeda into the CNS fluid compartment where the tumor is located.
Catheter Implantation
The Ommaya reservoir is a soft, plastic, dome-shaped catheter commonly implanted under the scalp in LM patients, providing direct drug access to the ventricle, beyond the blood-brain barrier.
CSF Infusion
Using the Ommaya reservoir, the drug may be directly injected in the cerebrospinal fluid (CSF), the clear fluid surrounding the brain and spinal cord.