With neurological diseases predicted to rise exponentially across the globe, whether resulting from the extension of life expectancy or aging populations, more novel solutions are necessary so that health care can stay ahead of the game.
Neurological diseases, disorders and injuries – such as Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, brain tumours, and Parkinson’s disease – are some of the leading causes of disability amongst the Canadian population that take a toll not only on the patient and the Canadian health care system, but also have a significant economic impact.
To date, these neurological diseases and disorders have been largely incurable and tend to worsen over time, typically involving invasive procedures by scientists and researchers as they attempt to penetrate the blood-brain barrier. Remarkable as the blood-brain barrier is to neuroscience, it is extremely fickle and highly selective, restricting the paracellular diffusion of water-soluble substances from the blood to the brain. Despite it being nature’s evolutionary way of protecting humans’ greatest asset, it does not come without its faults. Its defensive properties impede the way for medicinal compounds to penetrate the barrier and deliver the potential life-saving properties to their destination point.
Statistics have shown that 1 in 6 will acquire a neurological disease, totalling about 1.25 billion people worldwide. It is for this reason Canadian company Bioasis Technologies Inc. is determined to deliver effective treatments to patients who suffer from one of these diseases.
“The key thing if you have brain cancer is that the only therapeutic benefit will come from a direct infusion into the brain – like drilling a hole in the head – and while some people are trying to inject into the spine and pump it into the central nervous system, none of it has worked.” – Mark Day
Vancouver-founded Bioasis has undertaken this challenge by focusing on a single goal: revolutionizing science by transporting therapeutic payloads across the blood-brain barrier and into the brain. They have developed and are in the process of commercializing their proprietary brain delivery technology, the xB3 platform, to make life-saving drugs brain-penetrant and deliver those therapies at a therapeutically relevant dose.
Inception of the company began back in 2007 when researchers discovered an extremely large peptide that was capable of crossing the blood-brain barrier with a substantial amount of cargo. The team did a couple of experiments with Doxorubicin in mice models with cancer that positively showed higher survival rates and became the first proof of concept. The also acquired Trastuzumab data whereby they transferred Herceptin across the blood-brain barrier in sufficient quantities to reduce the number of tumours.
Although researchers have been speculating about less invasive methods that will penetrate the barrier, Mark Day, the president and chief executive officer of Bioasis, comments: “The key thing if you have brain cancer is that the only therapeutic benefit will come from a direct infusion into the brain – like drilling a hole in the head – and while some people are trying to inject into the spine and pump it into the central nervous system, none of it has worked. The brain methods do work, so there is at least some data if you inject it that you can get it approved for efficacy for small groups of patients.”
Recently, MedImmune, a wholly-owned subsidiary of AstraZeneca, did an independent validation of Bioasis’ xB3 platform technology that transpired incredible results. The study found that the xB3 fusion protein maintained the systemic pharmacokinetics of its payload and had significantly improved and sustained brain exposure of the payload molecule. It provided evidence that Bioasis’ platform technology was recombinant and chemically conjugated drugs across the blood-brain barrier to increase brain exposure.
These data and validation from MedImmune provide promising results that it will work in a phase 1 study. Bioasis figured out that once they attached Trastuzumab to 12 active amino acids (peptide 12aa), 10 times the amount of the drug passed through the blood-brain barrier. Mark Day adds: “What is really important is that once the drug is in the brain it hits the tumour. Looking at these results you can see that there are significant therapeutic doses in the brain and in controlled regions. This shows us that the drug gets into the brain, it gets to the site of action, and binds to those specifically where there are HER2 positive cells.”
Bioasis has four main programs:
- xB3-001: Brain Metastases, which is the most common form of brain cancer in adults and is often fatal due to anti-cancer drugs being unable to pass the blood-brain barrier, and is also the program that will progress first to human trials in 2019;
- xB3-002: Glioblastoma, one of the most aggressive cancers that originates within the brain, with 80 per cent of diagnosed primary malignant brain tumours as malignant gliomas. It is considered the deadliest form of brain cancer due to its high infiltration of surrounding brain tissue. This program is being done in collaboration with Minerva in Copenhagen;
- xB3-007: Neurodegenerative diseases, which entail a progressive loss of function by the neurons in the brain and in being diagnosed at an alarming rate partly due to an aging population; and
- xB3-008: Lysosomal storage diseases, which are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies.
If the xB3-001 and xB3-002 programs are successful, it would be the first time in human history that medicine for cancer has been properly received into the brain without having to drill into the patient’s head. This will be a breakthrough in science and open the doors to a floodgate of scientific possibilities.
Bioasis’ technology platform has been so efficacious that there simply have not been any competitors that have been able to keep up. The receptor with which they work with is ubiquitous to the blood-brain barrier walls, providing more possible passageways for medicine to penetrate through. This receptor, even in its natural form, is critical in cleaning out harmful tissues in the brain like Alzheimer’s disease for example and is necessary to maintain brain integrity.
Bioasis’ technology platform has been so efficacious that there simply have not been any competitors that have been able to keep up. The receptor with which they work with is ubiquitous to the blood-brain barrier walls, providing more possible passageways for medicine to penetrate through.
“The other thing that differentiates us is how we develop drugs,” says Mark Day. “We know that if you engage the target and prove that the target engagement drives biologic effect – to schizophrenia that would be a lowering of dopamine – then you have a good sense of patient population. So, for some of these diseases, there is a very strong genetic basis to them and subsequent diseases that gives us the mechanism to recruit the patient who is most likely to benefit from the medicine in the first tranche.
The proof of principal in the first point, get the proof of concept, on the back of a positive proof of concept then you would go earlier into the diseases. That’s what we can do with our last two neurodegeneration products. Basically, we go into a smaller niche indication, get the proof of concept and then expand it into other disease areas. That’s been the strategy,” he adds.
With recent editions to their scientific advisory board and looking ahead to put them in the best financial position for Nasdaq, the future looks promising for this biotechnology company. Penetrating the blood-brain barrier has been an arduous task, but if Bioasis is successful, their technology will revolutionize the treatment for neurodegenerative diseases and brain tumours, potentially slowing the progression of disease, and maybe someday offer a cure.