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The blood-brain barrier (“BBB”) consists of a vast network of capillaries that deliver oxygen, nutrients and other necessities to brain cells and carry waste materials away. As in the rest of the body, the walls of the BBB capillaries consist of a single layer of endothelial cells. However, the junctions between the endothelial cells of the BBB capillaries are tightly joined so foreign substances, harmful as well as beneficial, are prevented from passing from the blood, between the cells and into the brain tissue.
The endothelial cells that form this formidable barrier allow the transport of desirable molecules between the blood and the brain. Unique physiological mechanisms allow sugars, minerals, proteins, waste materials and other substances to pass through the BBB, maintaining the delicate chemical balance of the brain.
This exchange of substances takes place through channels and receptors found on the surface of the BBB endothelial cells. For instance, melanotransferrin (“MTf”), the protein upon which biOasis’ Transcend is based, attaches itself to receptors on a BBB endothelial cell and is ferried through the cell into the brain where it delivers its normal payload of iron.
Making adaptations to an innate transport system, such as MTf, in order to carry therapeutics across the BBB could allow for an effective, safe and non-invasive drug-delivery system, which is what biOasis has done with Transcend.
A system that allows the transport of therapeutics across the BBB would address a large unmet medical need in neurological medicine. Due to the BBB, over 98% of small molecule drugs and almost 100% of larger biologic drugs (antibodies, enzymes, etc.) cannot enter the brain at therapeutic concentrations.
The BBB and existing delivery mechanisms of therapeutics to the central nervous system (“CNS”) are the limiting factors in developing treatments for many neurological diseases.
Via Krishan Maggon
biOasis’ Transcend Platform is a group of proprietary technologies designed for the transport of therapeutic agents across the blood brain barrier (“BBB”) and into the brain tissue. The delivery of therapeutics across the BBB represents the single greatest challenge in the treatment of over a thousand common and rare diseases of the brain and central nervous system. The development of an effective method to deliver therapeutics across the BBB has been considered for decades to be the “Holy Grail” of neurological medicine.
Transcend ProgramMTfTranscend is based on the naturally occurring transport protein, melanotransferrin, also called MTf, CD228 and p97. Found at low concentrations in the blood, MTf is able to cross the BBB through a process called Receptor Mediated Transcytosis (“RMT”) where MTf molecules attach to receptors on the cells of the BBB. MTf is then pulled through the cells and into the brain where the MTf molecules can deliver their payload.
With biOasis’ proprietary Transcend carrier, the MTf protein can be attached to therapeutics of varying sizes or types. When infused or injected as a therapeutic, the resulting structure attaches itself to a BBB receptor and is pulled across the BBB where the therapeutic payload is delivered to brain.
biOasis has shown that Transcend can deliver a wide variety of therapeutics to brain, including antibodies, enzymes, siRNA and small molecule drugs, which together are expected to treat neurological diseases in several areas, including brain cancers, neurodegenerative and metabolic diseases.
MTfpThrough extensive research, the biOasis team identified the peptide portion within MTf that was responsible for crossing the BBB. The peptide, named MTfp, was shown to transport therapeutic agents across the BBB more readily than the original Transcend. biOasis filed patent protection for the peptide and its related forms, which would result in extending the Company’s intellectual property for another 20 years. The peptide was branded “MTfp” and is now the Company’s main focus.
Benefits of The Peptide DiscoveryMTfp is less than 2% the size of the original MTf protein, which is advantageous because:
MTfp has a higher commercial value than MTf.MTfp can be produced at a fraction of the cost of MTf.Quality Assurance is far easier with MTfp than with MTf.MTfp allows for rapid and reproducible synthesis of Transcend-based therapeutics.MTfp has a longer shelf life than MTf, resulting in longer storage times.MTfp can be linked to therapeutics with greater control and efficiency than MTf.biOasis is actively engaged in the development and commercialization of its proprietary Transcend Platform and a newly discovered peptide derived from MTf for the transport of therapeutic agents across the BBB to the central nervous system (CNS).