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Paul Brennan of Canadian Start-Up, NervGen Corp, explains a breakthrough on help for MS and Spinal Cord injury patients

Vancouver-based NervGen Pharma Corp. is a publicly-traded biotech company that works to develop treatments for patients with medical conditions related to nerve damage.

The company evolved from a story of personal tragedy.  In 2016, the daughter-in-law of one of the co-founders, Dr. Harold Punnett, fell and became a complete T-11 paraplegic from the spinal cord injury sustained. Codi’s life, and her family’s, changed forever.

Dr. Punnett set out on a quest to learn more about what could be done for spinal cord injury.    He came across many alternative approaches but among them was the work of Dr. Jerry Silver at Case Western Reserve University.  Their meeting led to the formation of the NervGen Pharma Corp. in 2018. 

While spinal cord injury was an initial driver behind the company, it is not a central theme.  Their research’s potential has rapidly become more far-reaching.  NervGen now aims to help patients with many different conditions, including but not exclusive to spinal cord injury.

In November 2019, Paul Brennan became President and CEO of the two-year-old company.   Paul is well known in the pharma world with a long and distinguished career in the industry and chatting with him was fascinating.

Paul pre-NervGen

Paul was born in Bristol, UK, but his family moved to Canada while he was still very young.  From early childhood, he was fascinated by biology and decided to study for a BSc (Hons) in Life Sciences and then an MSc in Physiology from Queen’s University in Ontario, Canada.  He says the plan had not been to go to grad school, but he had such a fantastic tutor in his third year that he signed up.

Paul then went to work for AstraZeneca, initially in Canada and then in both Sweden and the UK. By happy chance, Paul ended up living only half an hour from his aunt and cousins in the UK.

He had been working in regulatory affairs, but, by age 27, he could go no further in his career at AstraZeneca within the R&D function at the company without a Ph.D.   Paul decided to swop to the business development side and spent the last third of his time with AstraZeneca there instead.  He stayed with AstraZeneca for thirteen years.

A series of positions, predominantly in business development, followed for Paul at AnorMed Inc., Aspreva, Tekmira Pharma, InMed Pharma, and Aquinox Pharmaceuticals.  In between working for various companies, he has also spent time with his own consulting practise, Pacific Bio Partners.  

Paul’s impressive record shows a list of over $3 billion in value in licensing and business development transactions; he has also contributed to the commercial or regulatory development of over ten products that have moved from development stage to gaining regulatory approval.

Paul attributes his successful progression to two reasons.  He always took an interest in areas outside the scope of what he was doing.  For example, while he was in regulatory affairs, he still kept up to date in sales, marketing, and business.  It is his top tip for advancing your career.

The other point is that he is a strategic thinker, and this is hugely important.  Paul also played a lead role in the sale of Aspreva to Vifor Pharma, of AnorMed to Genzyme, and the merger between Tekmira and OnCore Biopharma to form Arbutus Biopharma.  He says these achievements have included an element of good timing, being in the right place at the right time, and sometimes just going along for the ride.

Paul had met Bill Radvak, Chairman of NervGen, approximately three years ago.  Bill was often asking Paul for his advice. Paul offered to help guide others involved in the start-up and became an advisor to NervGen’s Board on both strategy and business development.  In particular, he consulted on setting the company up in a workable financial way and organizing a strategic path forward.  Paul also introduced them to Ernest Wong, who became their first CEO.

NervGen’s unusual route for funding:

It is hugely unusual for a two-year-old start-up to be a publicly listed company.  Paul believes they are one of only three preclinical companies in their sector (central nervous system) globally.   Usually, companies would be venture capital-backed at this point.

However, they have an exceptionally strong investor group who supported them in seed funding and IPO, making listing possible.  The result is that they are obtaining drip-feed financing every year or so and do so by creating value each time. 

Ernest, while commercially astute and excellent in operations, had no experience of working in capital markets after the IPO, so Paul agreed to step in as President and CEO.   The way they are funded means a considerable amount of work for Paul and a curious situation.  They are still a start-up, with only a few employees, yet floated and currently valued at $65 million Canadian.  Paul is looking forward to delegating more in the future but is driven by the desire to find the best path to help patients.

NervGen’s Research and Development:

 

NervGen Corp - helping MS and spinal cord injury

NervGen’s core technology targets a novel receptor called protein tyrosine phosphatase sigma or PTPσ. 

They continued with Dr. Silver’s research, much of which focused on the glial scar, one of the body’s many responses to injuries, such as spinal cord injury.  This scar that forms in trauma cases should be protecting the area while healing, but a class of complex molecules that are produced as a result of the injury, called chondroitin sulfate proteoglycans, or CSPGs, end up  preventing repair and regeneration. 

Working with scientists from Harvard, Dr. Silver identified PTPσ as receptor in the central nervous system that interacts with the CSPGs and that is predominately responsible for impeding nerve regeneration and repair. With neurodegenerative diseases such as multiple sclerosis, or MS, or with Alzheimer’s disease, the quantity of CSPGs increases.   This means there is a barrier to healing with the CSPGs preventing the natural repair mechanisms that the body could use to overcome the damage cause by the disease.

NervGen’s lead product is NVG-291, which inhibits the receptor PTPσ in the nervous system and peripheral nervous system.  The compound works by binding to the PTPσ receptor, which then inhibits the downstream signalling of the receptor that would otherwise prevent the natural mechanism of nerve repair. Thus, by inhibiting the inhibition of nerve repair caused by the interaction between PTPσ and CSPGs, NVG-291 is expected to promote nerve repair. 

NervGen’s studies so far have shown treatment promotes the repair of damaged nerve systems and improves function.  Evidence is indicating that several endogenous repair mechanisms mediate their mechanism for nerve repair.  This gives potential to help treat nerve damage associated with both nerve injury (for example, spinal cord injury, peripheral nerve injury, traumatic brain injury, and stroke) and with neurodegenerative diseases (for example, multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson’s disease). 

Alzheimer’s disease cases have continued to rise over recent years but at the same time has been challenging to develop treatments for as scientists have not entirely understood what causes it yet.   We believed that amyloid plaques, clusters that form between nerve cells, are a cause for many years.  However, work along these lines has produced little positive result, and new research, NervGen’s among it, is developing technology that targets molecular pathways outside the amyloid-beta hypothesis.

So far, the strongest part of the company is its work towards help for MS  and spinal cord injury patients where they are achieving the highest evidential results; and investors are keen to support them.   It has genuinely revolutionary potential.

The Future for MS and Spinal Cord Injury

NervGen plans for NVG-291 to enter Phase 1 clinical trials in the first half of 2021.  They are working in Australia for this, so there have been relatively few delays from COVID-19.

Phase 2 is the efficacy studies, which will be carried out initially on spinal cord injury and MS.  These controlled studies will be either in Europe or North America. 

Paul says that the results so far, even with historically challenging indications such as spinal cord injury and stroke, have been truly incredible, and if only half of that can be achieved in humans, it will still be “a drastic game changer”.

People anticipate that they will sell after the Phase 2 trials.  Paul has other ideas.  He believes that committing to selling or financing at that stage leaves you vulnerable, so instead, he has a long-term plan to take them into Phase 3.  At the same time, if all goes well, they will make it known that they might be available to the big pharma at that point.

In the end, it is whichever gives the best opportunity to get the technology to market. Their work is all focussed towards enabling damage from both illness such as MS or injury such as spinal cord injury to be slowed down and potentially even reversed.

 

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