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The Revolutionary Co. That’s Breaking Through the Blood Brain Barrier

Dave Jackson Dave Jackson, Stockhouse
2 Comments| December 2, 2020

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(Click image to play video)

Delivery of therapeutics across the blood-brain barrier (BBB) and into the brain has been the single greatest challenge to treating hundreds of common and rare neurological diseases, including brain cancers, neurodegenerative diseases and metabolic disorders. Now, a cutting-edge biopharma company has developed and is commercializing its proprietary brain delivery technology – the xB3 platform – to make life-saving drugs brain-penetrant and deliver those therapies at a therapeutically relevant dose.

Bioasis Technologies Inc. (TSX-V.BTI, OTC:BIOAF, Forum) is a publicly-traded Company focused on developing its ground-breaking xB3 platform – a proprietary technology for treatment of central nervous system disorders in areas of high unmet medical need…including brain cancers and neurodegenerative diseases. The Company’s goal is to generate shareholder value by developing and commercializing its xB3 brain delivery technology.

In this intriguing and highly information vodcast, Stockhouse Media’s Dave Jackson was joined by CEO Dr. Deborah Rathjen and Dr. Mei Mei Tian, Vice President and the Head of External Research, to talk more about the amazing xB3 platform, how it works, its investment potential, and all things Bioasis.


SH: Doctor Tian, can you give us a bit of background history about yourself and how you initially entered into clinical research for Bioasis?

MMT: I got my undergraduate and graduate degree from the university of British Columbia in Vancouver Canada. For my graduate work at the university, I investigated the role of melanotransferrin in melanoma malignancy. During my post-doctoral career, I had the opportunity to work with Bioasis on its developmental projects associated with brain delivery. In 2012, I join the Bioasis team and along with the other scientists in the company, we worked on the early development and continued expansion of our proprietary blood-brain barrier technology, xB3.

SH: So, Doctor Tian, let’s talk a bit about the game-changing, proprietary X-B-3 platform. For our investor audience that might be new to Bioasis, how does it work and where does the company hope to take it?

MMT: The normal functioning of central nervous system is protected by the blood-brain barrier, which regulates the brain homeostasis and the transport of endogenous compounds. The highly selective regulation of the brain homeostasis by the BBB presents a major obstacle in the incapability of small and large therapeutic compounds to reach the brain. We have developed at Bioasis the xB3 platform that is consist of a peptide of 12 amino acids which has demonstrated high CNS transport rate, and can facilitate the transport of a wild range of payload types across the BBB into the brain tissues. These therapeutic compounds range from oligonucleotides (siRNA) and small molecules to large biologics (enzymes and antibodies). Our platform traverse the BBB via LRP-1 receptor in a process call receptor-mediated transcytosis, similar to how the traditional TfR works…except LRP-1 receptor is highly expressed on the BBB and in the brain, and has a higher capacity and transport rate compare to TfR.

Our internal pipelines consist of carefully selected programs involving previously approved drugs that were effective in treating peripheral symptoms but failed to treat central nervous system manifestations of diseases because those drugs did not cross the BBB, such as our lead program xB3-001 involving trastuzumab for treatment of Her2+ breast cancer brain metastasis. By fusing or conjugating our xB3 technology to these therapeutics, they become brain penetrant new molecular entities. The diversity of our pipeline will help mitigate risk as we examine a variety of payloads as well as a diversity of indications of high unmet medical needs such as brain cancers and neurodegenerative diseases. In addition to our pipeline, we also have collaboration and partnerships to work on novel biologics and targets, as well.

SH: Doctor Tian, neurological diseases affects 1.25 billion people worldwide and the incidence of these disorders is only increasing. How can X-B-3 effectively treat many CNS problems?

MMT: xB3 is a delivery platform and is responsible for facilitating the transport of payloads across the BBB. With the high expression of LRP-1 receptor throughout the brain, especially in critical regions of brain and brain cell types, our platform will enable many previously approved drugs, that are effective in treating peripheral symptoms, to access their corresponding targets within the brain. For example, our xB3-001 molecule enable trastuzumab which is effective in treating Her2+ breast cancer to treat HER2+ breast cancer that has metastasized to the brain.

SH: Doctor Tian, I mentioned a bit about the blood-brain barrier in the intro. Can you explain how blood-brain barrier plays a vital role in protecting the brain from blood-borne disease and toxic compounds?

MMT: The largest obstacle to effective drug brain delivery is the blood brain barrier (BBB), more precisely it is a network of specialized capillary endothelial cells that protect the brain from harmful substances while facilitating access to the essential nutrients to support proper function. While peripheral capillaries in the body allow relatively free exchange of substances between cells and tissues, the endothelial cells that form the BBB strictly regulate the transport of substances into the brain using both physical and metabolic barriers. These barriers regulate brain homeostasis (the balance of electrolytes, glucose, nucleosides, and amino acids) through multiple efflux and uptake transporters, metabolic enzymes, low pinocytotic activity, and low paracellular permeability. The impermeability of the BBB results from tight junctions between capillary endothelial cells formed by cell adhesion molecules. This heavily restricting barrier protects the CNS from toxins, pathogens, inflammation, injury and disease.

SH: Doctor Tian, we all know about the devastating personal, medical, and economic effects of the global opioid epidemic. Another important component of X-B-3 therapy is its positive effect in non-opioid pain management. Can you discuss how this all works?

MMT: Specifically with neuropathic pain, it arises from damage or lesion of somatosensory nervous system. For targets located outside the CNS, there are promising biological interventions, but targeting within the CNS has remained challenging due to the BBB. IL-1, for example, is a proinflammatory cytokine that has role in development, maintenance and propagation of pain. IL-1 expression is increased in conditions associated with pain, and hyperalgesia in periphery and in CNS. However, IL-1 inhibitor such as IL-1 receptor antagonist (commercially available as Kineret) act as an agent that binds non-productively to the IL-1 receptor that IL-1 binds…therefore preventing IL-1 from sending signals. In our previous study with Medimmune, peripheral delivery of IL-1 receptor antagonist does not elicit any reversal of pain in the neuropathic pain animal model, however, the invasive intrathecal delivery by means of direct injection into the cerebrospinal fluid within the intrathecal space of the spinal column can demonstrate dose-related reversal of pain temporarily. With addition of our xB3 peptide to IL-1 receptor antagonist, reversal of pain in the animal model was achieved through peripheral delivery, specifically subcutaneous injection, with higher efficacy as the more invasive intrathecal delivery method. Therefore proving that our platform is capable of bring biologics across the BBB and engaging targets associated with pain in a minimal invasive manner.

SH: One the business side of things, Doctor Rathjen, the recent announcement of XOMA Corporation’s “acquisition to the rights to future milestone and royalty revenue from Bioasis”. Can you walk us through this agreement and what it means to company shareholders and potential investors?

DR: Yes, of course Dave.

XOMA’s business is as a royalty aggregator and as our shareholders know the companies have an agreement that was put in place in early 2019 for the purchase of royalties from certain of Bioasis licensing transactions. The first transaction with XOMA involved our Prothena licensing deal and the second has been our most recent deal with Chiesi Group, a strategic alliance around four enzymes for the treatment of Lysosomal Storage Disorders.

Lysosomal Storage Disorders are rare, genetic disorders of metabolism that frequently have severe neurological complications in addition to peripheral complications.

In respect of our Chiesi deal, in exchange for a US$1.2 million upfront payment, XOMA will receive a low single-digit royalty on the future net sales of each of the four Chiesi Group-Bioasis enzymes and an undisclosed share of the up to US$138 million in potential milestones due to Bioasis under its agreement with Chiesi Group.

The additional immediate funding secured has allowed Bioasis to deploy additional capital to progress its unpartnered pipeline programs targeting IL-1 driven neuroinflammation including pain – or xB3-004, Gaucher’s Disease, Parkinson’s disease and Lewy Body Dementia – or xB3-007 and a new program targeting Fronto Temporal Lobe Dementia.

Importantly the additional capital extends our runway as we look to secure further technology validating partnerships.

SH: Can you also tell us the core benefits to the Chiesi Group-Bioasis strategic alliance?

DR: We were very pleased to have entered into this agreement and excited to be working with Chiesi Group, a global company with a strong commitment to bringing innovative treatments to patients with LSDs.

As I have already indicated neurological complications of LSDs remain largely untreatable when peripheral symptoms of disease respond to enzyme replacement therapy. Our xB3 BBB drug delivery platform has the potential to significantly advance the treatment of LSDs and to improve the use of enzyme replacement therapy, solving one of the major unmet clinical needs and improving the lives of patients.
It is an important validation of our business model, to purposefully partner our xB3 technology with those companies that have the clinical development and marketing expertise to commercialise new treatments for serious, life-threatening diseases.

Another important benefit came from the upfront payment which able to be used re-charge R&D investment in our preclinical programs and to paydown debt. That was a very welcome boost.

SH: And a major milestone achieved. Can you tell us a bit about the recent issuance of an X-B-3 US Patent?

DR: The issuance of this patent by the U.S. Patent Office represents another major milestone for our intellectual property protection around our core assets. Examples of therapeutic areas covered by the patent include lysosomal storage diseases – a core area of expertise for Bioasis. Adding to the already granted patents in the U.S. and around the world, this further strengthens and reinforces our standing around our core technology and our xB3™ programs, including xB3-007 and xB3-008.

The Bioasis business model is based on the strength of these assets and the intellectual property that is protected by our broad patent portfolio.

SH: Can you discuss the long-term strategy for the company? What should investors be looking forward to…from Bioasis?

DR: Our long-term strategy continues to be to progress our pipeline and to partner our xB3platform technology in a way that adds value to our Company for the benefit of our shareholders.

We are progressing our preclinical pipeline – and I have indicated those programs we are focusing on – and investors can expect news and data from those programs.

We are also progressing new deals on the business development front.

SH: And finally, Doctor Rathjen, what can you tell our investor audience regarding the current valuation of your stock and why you think it’s a good buy right now?

DR: The delivery of medicines across the blood-brain barrier has been the single greatest challenge in the treatment of many neurological diseases. For generations of people suffering from for example, brain cancers and neurodegenerative diseases, the blood-brain barrier represents a wall separating patients from effective treatments and hope.

So…First and foremost we have world leading technology that not only enables the delivery of important medicines across the blood-brain barrier and into the brain – it is delivering hope.

We also have a strong pipeline of new preclinical treatments – each one a potential blockbuster, each able to help some of the 1.25 billion people worldwide for whom no effective treatments exist.

And…our approach and business model is validated, validated through collaborations with commercial partners that are actively seeking to develop and bring to market next generation medicines based on our XB3 technology.

For more information, visit

FULL DISCLOSURE: This is a paid article produced by Stockhouse Publishing.

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December 7, 2020

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December 3, 2020

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