biOasis Technologies Inc. Blood Brain Barrier Platform Attracts Majors

biOasis Technologies Inc. (TSX.V:BTI) (OTCMKTS:BIOAF) use of peptides to transport therapeutic drugs across the blood brain barrier is attracting the attention of major biotech partners. Currently, the company has licensed its platform for research purposes to AstraZeneca plc (ADR) (NYSE:AZN) (LON:AZN) subsidiary Medimmune Ltd. Medimmune has undertaken evaluation of the therapeutic effect of its pre-clinical assets with next-generation versions (initially MTfp) of biOasis’s Transcend brain delivery platform.

The preliminary data from the March 17, 2014 agreement is under active assessment by both biOasis and MedImmune.

Download the full Midas Letter Research Report on biOasis Technologies Inc.

AbbVie Inc (NYSE:ABBV), a spinout of Abbott Laboratories (NYSE:ABT) concluded a 2-year collaboration with biOasis in January 2014, and the two companies are in discussion on a further partnership.

AbbVie and Medimmune Seeking Blood Brain Barrier Solution

According to BCC Research, all of the top pharmaceutical companies are involved in BBB technology or have explored it. Six of the top 10 companies having active licensing deals with BBB technology companies that have chosen to specialize in the competency of delivery compounds, including MedImmune (AstraZeneca) with biOasis (that is looking at lysosomal storage disease), GlaxoSmithKline with Angiochem (also looking at lysosomal storage), Lundbeck with Ossianix and Nanomerics (looking at several targets).

Rather than develop this expertise in-house, which pharmaceutical companies have tried to do, the emerging industry model is for larger companies to license or acquire this expertise – with the exception of Genzyme that developed its own BBB-branded technology called LipoBridge – now called Cerense, after being bought by UK-based Pharmidex.

Today, three compounds using BBB technology are currently in the clinical development pipeline, but by 2019 they will number approximately eight. Research pegs the global market for CNS/BBB technology at $80 billion annually. The market is expected to grow to significantly by 2019, and register a substantial CAGR from 2014 through 2019. According to biOasis CEO Rob Hutchison, if the company’s technology is deployed commercially, the market could be worth as much as $200 billion.

What is the Blood Brain Barrier?

The Blood Brain Barrier (BBB) is the protective barrier that separates the brain from the circulatory system, which blocks harmful compounds from entering the brain tissue. It is a capillary network of tightly woven endothelial cells lining the blood vessels in the brain, regulating transport of essential molecules and maintaining a stable environment.

It is a highly sophisticated structural design of the human body which determines what fluids are permitted in and near the brain and which would prove harmful. Capillaries which surround the connective tissue and neuroglia known as astrocytes “stand guard” and select the substances which are permissible.

Glucose, water, lipid soluble compounds, carbon dioxide, and oxygen pass through the Blood Brain Barrier without difficulty. Inorganic compounds may pass but will be permitted more slowly and more hesitantly. The concentration of ions within the brain needs to vary from the concentration within the bloodstream. Antibiotics, most toxins, proteins, lipids, urea, insulin, and creatine are prohibited from passing through the barrier.

This is the body’s natural defense mechanism against toxins penetrating the brain, and is how we protect ourselves from cerebral invasion. The problem is, however, when serious diseases of the brain manifest, it has proven nearly impossible to transcend the BBB with therapeutic drugs in sufficient quantity to have an effect on the targeted malady without causing toxicity in the brain.
The barrier provides such a protective shield to the brain that approximately 98% of small molecule drugs and 100% of large molecule drugs cannot cross it. Advanced BBB drug delivery technologies essentially produce central nervous system (CNS) drugs that can pass the BBB using a platform technology or drug delivery technologies.

Download the full Midas Letter Research Report on biOasis Technologies Inc.

biOasis’ Patented Transcend Platform

biOasis’ principle product offering to pharmaceutical companies seeking ways to deliver therapeutic compounds across the Blood Brain Barrier is called its Transcend Program. The technology relies on a naturally occurring transport protein (melanotransferrin, also called MTf, CD228 and p97) that routinely cross the BBB through a process known as 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.

The company owns approximately 30 U.S. and foreign patents/applications related to p97 as a BBB delivery vector and as a biomarker for Alzheimer’s disease. In regard to biOasis’ lead programs in oncology it owns seven U.S. and corresponding foreign patent applications in the area of brain-penetrating antibodies for the treatment of brain and other cancers. Parts of these applications are specifically directed to the MTf-TZM (formerly ‘BT2111’) program for the treatment of brain metastases of HER2+ breast cancer. These patents, if issued, would provide biOasis with protection through 2032, not including any patent term adjustment. biOasis business model includes the process of aggressively building the Transcend patent portfolio through the filing of new patent applications directed to various improvements in the use of Transcend to shuttle therapeutic compounds across the BBB.

MTfp (formerly ‘Transcendpep ‘)

In April 2014, biOasis announced a new family of peptides (naturally occurring biological molecules) that it believes can ‘conserve and enhance’ the transportation of therapeutic molecules across the BBB in its Trascend platform. Referred to as ‘MTfp’ (formerly ‘Transcendpep’), recent studies demonstrated in animal models a capability to deliver such therapeutics across the BBB regardless of molecule size or composition.

According to the company’s most recent Management Discussion and Analysis,
“This peptide family, the second generation of Transcend, offers multiple advantages compared to Transcend. The peptides can be synthesized by standard methods in vitro and a wide variety of peptide-cargo conjugates with different applications to a range of diseases can be produced simply and predictably. The peptide vectors have the potential to be particularly well suited to coupling to small molecule chemotherapeutics and other drugs.

Thus development of new drugs using these new shuttle vectors will likely be accomplished much more quickly and with higher precision. This new family of novel chemical entities provides a strong patent position for the Company and its current and future partners. In preclinical animal models the peptide vector-conjugates have shown remarkable efficacy.

MTfp is now expressed as the vector for all of the Company’s fusion proteins: Herceptin (Trastuzumab) and the lysosomal enzymes (I2S and HexB).

MTfp-siRNA Program

In a study at the National Research Counsel of Canada, it was determined that the MTfp platform could effectively deliver therapeutic siRNA molecules across the BBB and into brain cells, which has important implications for many Central Nervous System (CNS) disorders and other debilitating brain conditions for which there is currently limited available drug therapies, thanks to the limitations imposed by the BBB.

Again from the company’s MD&A:
RNA interference (RNAi) of gene function can be triggered by small single-stranded RNA molecules (small-interfering RNA; siRNA), which function to silence target genes in a sequence-specific manner. Therapeutics based on siRNA may have the potential to reverse and eradicate human disease by targeting specific genes that cause or modify disease outcome. However, since siRNAs on their own do not cross the BBB, the targeting of genes within the brain was not assumed to be achievable.
biOasis has now demonstrated delivery of siRNA across the blood-brain barrier using its new peptide vector, MTfp. After systemic injection, siRNA coupled to MTfp was shown to shuttle into the brain and became localized within brain cells in a mouse model.

Since a variety of different siRNAs (specific for different disease-associated genes) can be delivered, this is a significant achievement for the Company and for the field of molecular therapeutics. MTfp-siRNA constructs thus become a potential cornerstone technology for development of new therapeutics for brain disorders, including, cancers of the brain, Alzheimer’s disease, Huntington’s disease, Amyotrophic lateral sclerosis (ALS) and other neuropsychiatric diseases and for a variety of neuromuscular diseases, pain and infections.”

An an independent pathologist at the The University of British Columbia in the Animal Care Unit, showed that the reduction of the activity of the target gene in the experiment announced on May 6th was between 40-50%.

Major Partnerships

biOasis’ ability to attract pharmaceutical companies who are eager to find a solution to the conundrum of delivering their therapeutic drugs into targeted sites within the brain is one of its key differentiators separating it from conventional therapeutic drug development companies. Follwing is an overview of the partnerships now in place:

• AbbVie Inc.
  biOasis began a collaboration with Abbvie in June 2012 which concluded in January of 2014 and the companies are continuing discussions regarding potential future research/work programs.
• Medimmune Ltd.
  Based on positive test results of the November 14, 2012 Medimmune / biOasis collaboration, biOasis announced in March 2014 that it signed an evaluation and license agreement with MedImmune. Under the terms of that agreement, MedImmune began the evaluation of the therapeutic effect of its pre-clinical assets with next-generation versions (initially MTfp) of biOasis’s Transcend brain delivery platform.

  The preliminary data from the March 17, 2014 agreement is under active assessment by both biOasis and MedImmune.

• UCB Pharma SA
  In December 2102, biOasis inked a research collaboration agreement with Brussels, Belgium-based UCB Pharma SA (“UCB”). In connection with this agreement, biOasis is conducting certain experiments to provide UCB with confirmation of the Transcend technology as it relates to the delivery to the brain of therapeutic compounds owned by UCB. The collaboration was completed in December 2013 and the companies are in discussions regarding the potential introduction of the MTfp program into a work program with UCB.
• University of British Columbia (“UBC”)
  In partnership with the University of British Columbia, biOasis announced the commencement of a new phase of its Lysosomal Storage Disease program with a study focused on a knockout mouse model for Sandhoff Disease.The study will be assessing the use of therapeutics based on biOasis’ proprietary Blood-Brain Barrier vectors, MTf and MTfp, to correct enzyme deficiencies within the Central Nervous Systems of genetically engineered animals deficient in the enzyme β-hexosaminidase subunit beta (“HEXB”), which is functionally deficient in sufferers of Sandhoff Disease.

Other agencies that biOasis is partnering with include:
• Brains for Brain Foundation
• National Research Council
• Texas Tech University
• NSERC (Natural Sciences and Engineering Research Council of Canada)
• British Columbia Cancer Research Centre.

In Summary

biOasis is in an enviable position within the Life Sciences sector in Canada. As a developer of what is essentially a transportation technology (as opposed to a therapeutic drug developer), biOasis will never be subjected to the uncertainty of multi-stage clinical trials with its hopes for the future pinned on a single drug’s performance. Instead, those multi-million dollar processes are undertaken by the company’s partners, who license biOasis’ Transcend platform to perform the function of delivering their therapeutic compounds across the Blood Brain Barrier.

The company’s performance to date indicates the committment of existing shareholders to the future success of the platform, and the expensing of clinical trial costs to its partners suggests that future shareholder dilution will occur on a limited basis relative to conventional therapeutic drug developers.

For risk-tolerant investors seeking exposure to a solution for the ‘holy grail’ of Central Nervous System affliction treatment, biOasis may be worth a long hard look.

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