Canadian company ProMIS Neurosciences targets Alzheimer’s disease

Insight, Medical, Technology — By on May 31, 2017 at 7:40 PM

Gene Williams of ProMIS Neurosciences.

Canadian company ProMIS Neurosciences targets Alzheimer’s disease

By James Brewer

A Canadian development-stage biotech company is using precision medicine to target what it says is the root cause of Alzheimer’s disease and amyotrophic lateral sclerosis (ALS), the latter also known as motor neurone disease.

Toronto Stock Exchange-listed ProMIS Neurosciences Inc is focusing on what it says is “game-changing” therapeutics for neurodegenerative diseases. It is aiming for a breakthrough that has eluded the giants of the industry, who so far have been unable to offer therapies to stop progression of Alzheimer’s.

Big pharma has spent billions of dollars on failed, or partially successful clinical results. Such failures have disappointed sufferers and their families – almost everyone has a family member affected by Alzheimer’s disease, a growing cause of death.

Treatment for this infirmity, which results in total – direct and indirect – annual US healthcare costs of up to $500bn, a figure expected to triple over next 10-15 years, is said to be “the greatest unmet need in medicine” and stepping up to this is a “massive market opportunity.”

Gene Williams, executive chairman of ProMIS, has been in London and other European financial centres to report to investors on his company’s advances and strategy for continuing research and trials.

Costs to society of Alzheimer’s.

A healthy human brain hosts around 100bn neurons, and many of these are killed before symptoms of one of these crippling diseases emerge. What is it that kills these neurons in the brain? Protein fragments in the brain known as amyloid beta are normally broken down and eliminated, but they can aggregate into plaques.

If your immune system does not clear out the toxic oligomers (strains) of amyloid beta, they start replicating themselves and killing neurons, and eventually your defences break down.

ProMIS has designed means to block the toxic oligomers which spread through the brain – the fundamental driver causing the death of neurons, and cognitive decline. “Our product halts that process and stops the toxic oligomers from spreading,” said Mr Williams.

He said that results of industry trials clearly indicated that to succeed, products must target the toxic prion (tiny disease-causing agents) form of amyloid beta, rather than the other forms of amyloid beta.

The failures came from a misunderstanding that plaque was the problem: now we know that this is not the case, insisted Mr Williams. A smaller subset of amyloid beta was responsible for killing neurons, and not plaques.

With products that bind monomers before they combine into oligomers “you waste all your ammunition.” Failures arise because there are three or four strains of toxic oligomers.

Root and route of Alzheimer’s.

None of the tested clinical agents directly or effectively targeted toxic oligomers until Biogen (a Nasdaq-listed company based in Cambridge, Massachusetts) trialled its investigational compound Aducanumab: that treatment effectively targeted oligomers (not monomers) but failed to do so selectively, said Mr Williams, who added that Aducanumab also targets plaque, which contributes to a major side effect.

The ProMIS process starts by using its proprietary technologies to identify as targets for antibody drugs and diagnostics specific targets (epitopes) on the prion forms of misfolded proteins, which cause the development and progression of Alzheimer’s and ALS. Diagnostics is heading to detect different toxic oligomer strains of amyloid beta in cerebrospinal fluid and blood.

At least the setbacks elsewhere in investigation mean that “we as a community understand Alzheimer’s much better, and the science points the way to effective therapy,” said Mr Williams, who has had a career in drug development, healthcare and entrepreneurial deal-making. The playbook for the most successful products has become learning from the early missteps, and creating an even better product, he said.

Alzheimer’s is not usually hereditary, but there are some hereditary factors that diminish your ability to protect yourself. Everyone has well-formed toxic oligomers.

Some 95% of sufferers are 65 or older. Ideally, “if we can screen everybody in their 50s and 60s, we can identify the disease process, treat and prevent – that is the long-term potential,” said Mr Williams. The treatment would be by way of infusion into the bloodstream.

Such are the costs of care for Alzheimer’s that on current trends these could bankrupt Medicare, the US federal health insurance programme for people aged 65 and older and those with certain other categories of disability.

In ALS, the muscles are paralysed as neurons perish, and patients lose the ability to speak and to swallow. The best-known personality living with the disability is Prof Stephen Hawking, who was diagnosed at the age of 21, and remarkably has survived for more than 50 years to lead a brilliant scientific career. Some people survive a mere six months.

Publicly traded on the Toronto Stock Exchange under the symbol PMN, ProMIS has a market capitalisation of some $60m. The company is planning to pursue a listing on Nasdaq, probably in 2018. It raised C$7.7m in four rounds since July 2015, including in February 2017 private placements with gross proceeds of $2.7m.

“We are not raising money now, but we will be in the future,” said Mr Williams.

Market conditions suggest that the ultimate destiny for companies of this type with limited financial resources is likely to be partnership with a pharma major, or absorption by such a player.

ProMIS, which is at the preclinical stage, says that its proprietary technology “allows us to act faster than any competitor. Our portfolio has the potential to change the standard of care in Alzheimer’s disease.” It admits that although it may not become “first in class” ahead of one of its rivals, it would create a “best in class” offering.

It says that results announced in January 2017 for its lead product PMN310 showed prevention of short term memory loss when administered to mice. PMN310 is on track for IND submission (clinical trial initiation) in late 2018, to be followed by a phase one single ascending dose trial in 2019, and phase two proof of concept trial for completion in 2021.

During the company’s latest presentations to investors, a video message was relayed from renowned biotech specialist Anthony Giovinazzo, who in March 2017 was appointed to its board.

Mr Giovinazzo is president and chief executive of Sunovion CNS Development Canada ULC. As head of Cynapsus Therapeutics from 2009 to 2016 he led the successful purchase of that company by Sunovion Pharmaceuticals, part of Dainipon Sumitomo Pharma group of Japan. He was responsible for Cynapsus up-listing from the TSX Venture exchange to the TSX and then Nasdaq. Mr Giovinazzo said that having devoted most of his career to the development and commercialisation of therapies for neurodegenerative disease, he looked forward to leveraging his experience to support ProMIS Neurosciences.

The company website is www.promisneurosciences.com

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