I believe there is no end to learning and one’s own self-guided education. I believe the nature of life is a focus on learning which begins at birth to the moment you die. Always be curious. Follow the ‘golden rule’ by always treating others like you would like to be treated.
As a part of my series about “Big Ideas That Might Change the World in The Next Few Years” I had the pleasure of interviewing Paul Brennan, President and Chief Executive Officer, NervGen Pharma, a publicly traded (TSX-V: NGEN, OTCQX: NGENF) clinical stage biotech company dedicated to discovering and developing treatments for patients suffering from medical conditions related to nervous system damage, has over 30 years of experience in the pharmaceutical and biotech industries working in leadership roles in general management, corporate strategy, commercial planning, business development and regulatory affairs in Canada, Sweden, the United Kingdom, and the United States. Most recently Brennan’s experiences include senior business development and management positions in various biotech companies, including Aquinox Pharmaceuticals, Arbutus Biopharma, Aspreva Pharmaceuticals, and AnorMED Inc.
Brennan has a comprehensive list of business development and licensing transactions, totaling over $3 billion in value: he played key roles in the merger of Tekmira Pharmaceuticals and OnCore BioPharma to create Arbutus Biopharma, in the sale of Aspreva Pharmaceuticals to Vifor Pharma for $915 million and in the sale of AnorMED to Genzyme for $580 million. Prior to working in biotech, he held senior roles in Business Development and Regulatory Affairs at AstraZeneca. Brennan holds a MSc in Physiology, and a BSc (Hons) in Life Sciences from Queen’s University in Kingston, Ontario.
Thank you so much for doing this with us! Before we dig in, our readers would like to get to know you a bit. Can you please tell us a story about what brought you to this specific career path?
As Confucius said, “choose a job you love, and you will never have to work a day in your life.” I’ve always had a keen interest in biology, medicine and life science and I sought to find employment in this sector. After graduating, l had three months to find a job or I would have move back home with my parents in Ottawa. There’s nothing like that motivation to do everything in your means to find a way to meaningful paying employment. I worked with a recruiter, I answered ads in the newspaper (remember when people did that?) and even did some cold-calling.
Focusing in on the pharma sector, I actively interviewed for employment and received three job offers in one week. I accepted an offer with AstraZeneca, a global, science-led biopharmaceutical business, and eventually became a Director of Regulatory Affairs.
I’ve always been interested in areas beyond my individual responsibility. At AstraZeneca, I learned about sales, clinical research, marketing and manufacturing. I think that being interested in understanding the 360 degrees of a company is really important to building an impactful career.
Can you please share with us the most interesting story that happened to you since you began your career?
NervGen Pharma Corp’s IP was developed by leading medical researchers of degenerative brain disease and nerve damage, led by Dr. Jerry Silver in Cleveland, Ohio, where he is Professor of Neurosciences at Case Western Reserve University’s School of Medicine and adjunct Professor in the Department of Neurosurgery at the Cleveland Clinic Foundation. He is also credited in over 180 publications and is the recipient of several prestigious awards, including the Ameritec Prize for significant accomplishments toward a cure for paralysis.
Just after accepting the CEO position at NervGen, I met with Dr. Silver to review his animal model data which you can see highlights on this video. It was truly a ‘come to Jesus’ moment listening to Dr. Silver explain the data in an exciting and enthusiastic way. The recovery of locomotion with a significant subset of animals recovering fully, even in very severe spinal cord injury (SCI) models was remarkable. The animals also recovered voluntary bladder function; a critical unmet medical problem associated with SCI. The results were reproduced in multiple studies, labs and models — truly robust, reproducible data.
Dr. Silver first came to global prominence with a front page story in The New York Times entitled, “Rat Nerves Repaired and Rejoined with Spine” in the 1980’s which chronicles the first time crushed nerves were repaired. Dr. Silver is an extraordinarily accomplished and renowned spinal cord injury and regenerative medicine researcher and it was clear that NervGen Pharma Corp. exclusive worldwide licensing agreement with Case Western Reserve University to research, develop and commercialize this patented technology with potential to bring new therapies for spinal cord injury and other conditions associated with nerve damage was truly revolutionary.
Which principles or philosophies have guided your life? Your career?
I believe there is no end to learning and one’s own self-guided education. I believe the nature of life is a focus on learning which begins at birth to the moment you die. Always be curious. Follow the ‘golden rule’ by always treating others like you would like to be treated.
In the workplace, I fret over substance rather than style. For example, think about a company’s creation of a slide deck where there are ten people in the room focused on its development. So many times, people argue over style issues — the font, the color, the imagery, etc., — when there is no right way to do things. Content is the substance that is king. There is a right or wrong way to generate substance. Gaining consensus on the substance, including all the underlying messages, is what is most important and what I try to guide my team to understand.
Ok, thank you for that. Let’s now move to the main focus of our interview. Can you tell us about your company’s “Big Idea That Might Change the World”?
Injury or disease to the central nervous system (CNS) results in multifaceted cellular and molecular responses. One such response, the glial scar, is a structural formation of reactive glia (cells) around an area of severe tissue damage. The purpose of the scar is to encapsulate the site of the injury to prevent further damage and begin the healing process, but it ultimately inhibits the body’s reparative mechanisms. Dr. Silver discovered that a constituent of these scars, a glycoprotein called chondroitin sulfate proteoglycan (“CSPG”), is a major inhibitor of the body’s natural ability to regrow and regenerate the CNS.
Dr. Silver, together with scientists at Harvard University, identified protein tyrosine phosphatase sigma (“PTPσ”) as a key neural receptor that binds with the CSPGs in the glial scar. Dr. Silver’s research showed that PTPσ impedes nerve repair through its activation upon binding to CSPGs in the glial scar.
Multiple studies with animal models for several diseases and medical conditions have shown that treatment targeting PTPσ receptors with a compound developed by Dr. Silver and his research team, NVG-291-R (also called intracellular sigma peptide, or ISP in publications), promoted repair of damaged nerves and improvement in function.
NervGen is now developing NVG-291-R as the basis for its core technology. Our lead product, NVG-291, is a close analog to NVG-291-R.
Since the original discovery of NVG-291-R, the compound has been studied further by Dr. Silver and his collaborators, by NervGen and by a number of independent laboratories. There is now a large body of evidence to indicate that NVG-291-R’s mechanism for nerve repair is mediated by a number of endogenous repair mechanisms, including axon regeneration, plasticity, remyelination, autophagy and immune modulation. Furthermore, these repair mechanisms seem to be helpful in treating nerve damage associated with both acute nervous system damage injury (spinal cord injury, peripheral nerve injury, traumatic brain injury, and stroke) and with neurodegenerative diseases (multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson’s disease).
NervGen’s initial development programs are focusing on spinal cord injury, multiple sclerosis and Alzheimer’s disease.
How do you think this will change the world?
Conventional wisdom is that the central nervous system axons cannot regenerate after injury and that the nervous system cannot repair itself. The successful completion of NervGen’s technology on human subjects could rewrite the prognosis and provide life-changing therapies for people with spinal cord injury, multiple sclerosis and Alzheimer’s disease as well as other neurogenerative disease.
With the FDA’s approval of Biogen for Alzheimer’s patients — developed to decelerate the spread of the disease in its early stages — the spotlight is now on for finding therapies with a more meaningful response. NervGen’s technology platform has introduced a truly novel approach to treating Alzheimer’s disease.
We are preparing for a Phase 1b Clinical Trial in Alzheimer’s Disease and entered into a research agreement with Sylics Contract Research, to study the effects of NVG-291 in mouse models of Alzheimer’s disease.
Keeping “Black Mirror” and the “Law of Unintended Consequences” in mind, can you see any potential drawbacks about this idea that people should think more deeply about?
Quite frankly, no. If our technology enables a paralyzed person to regain mobility, restores recognition memory and rescues cognitive deficiencies for Alzheimer’s disease sufferers and reverses disease progression for those with multiple sclerosis, it is very hard to find a drawback.
Was there a “tipping point” that led the company to this idea? Can you tell us that story?
What led NervGen to our revolutionary ISP was a tragedy. Codi, the daughter-in-law of Dr. Harold Punnett fell into a hole and the integrity of her spinal cord did not survive the trauma. Codi remains a complete T-11 paraplegic. Dr. Punnett embarked on a neuroscience literature search and networking effort to find any way to improve Codi’s condition as reported in New Mobility magazine.
Dr. Punnett refused to accept the spinal-cord no-win-situation and the pessimistic mobility prognosis of Codi’s physicians. As a dental surgeon in British Columbia, Punnett is well-versed in medicine and physiology and he vigorously researched potential cures. Punnett met with Dr. Jerry Silver and was intrigued and brightened by his lab’s recurring data, which is that with injections of a peptide Silver’s lab invented, ISP (intracellular sigma peptide), Silver can cause severely spinal-cord-injured mice to walk again, to walk ostensibly normally.
NervGen was created to commercialize this ISP which we believe will change the world. The big idea that might change the world is that we have identified the chemical in the brain that is stopping the brain from repairing itself. Dr. Silver’s research focused on the glial scar which forms at sites of a physical injury such as spinal cord injury, as well as sites of inflammatory damage from neurodegenerative diseases such as multiple sclerosis and Alzheimer’s disease.
Our next tipping point will be when we demonstrate that the results from preclinical studies translate to humans, which we hope to see after our phase 1b and 2 trials. When that occurs, we expect to see considerable attention to the company, from patients, physicians, investors and from pharma. Our development programs focus on multiple sclerosis, spinal cord injury and Alzheimer’s disease with a Phase 1 trial in healthy volunteers to begin in Q2 2021. Our Phase 1b trial in Alzheimer’s disease is scheduled to begin in 2022/ Phase 2 trials in multiple sclerosis and spinal cord injury will begin in 2022.
What do you need to lead this technology to widespread adoption?
Widespread adoption of our ISP will happen when we are able to commercialize NVG-291 so that these revolutionary treatments are widely available; that’s the final tipping point.
What are your “Things I Wish Someone Told Me Before I Started” and why. (Please share a story or example for each.)
I wish someone at university told me to pay more attention to biochemistry and chemistry. My understanding is predominately physiology, but greater biochemistry/chemistry knowledge allows you to dig one layer deeper into the technology with greater ease. As someone who is committed to continually learning, I find my way to the knowledge I need, but it would offer me a leg-up to have taken more biochemistry coursework while in college.
Back when I was in high school, only girls were encouraged to take typing classes. As a course elective, girls were drawn to learn the skill of typing more than the boys since a good portion of employment was divided by gender-specific roles — some jobs designated for women, some for men. In our modern age “keyboarding” is vital for nearly all interactions with computers and other electronic devices. I wish I had known that a digital revolution would demand that each of us to learn to type in one form or another.
Like everyone else who grew up in the ‘70’s, I deeply regret not buying Apple stock when it first went public!
As a Canadian, hockey is our #1 sporting past-time. Like any memorabilia, vintage hockey cards, produced before 1980, are the rarest and most valuable. As a kid, in the 70s I collected every hockey card that was available. Unfortunately, I had not foresight to protect them and instead enjoyed experimenting with my cards on my bike so that the free end slaps the spokes going by as the wheel turns. At least it made a cool sound!
Can you share with our readers what you think are the most important “success habits” or “success mindsets”?
I believe the most important “success habits and mindsets” go back to what I said about always being curious. Be curious, think strategically, focus on the big picture and be open-minded. You are open to new ideas and ways of thinking when you are open-minded.
Being strategically focused is very important to my mindset. I do a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis when analyzing an opportunity. By comprehensively understanding the opportunity, I am able to maximize the opportunity while minimizing potential threats.
Some very well-known VCs read this column. If you had 60 seconds to make a pitch to a VC, what would you say? He or she might just see this if we tag them 🙂
NervGen’s technology is a big idea based on a unique discovery that will change the paradigm of how nervous system damage is treated. It is atypical for CNS products to have broad applicability like our technology. Our tech is based on multiple experiments and has been confirmed by many independent experts cross the world. We are on the verge of being broadly discovered.
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This was very inspiring. Thank you so much for the time you spent with this. We wish you continued success and good health!
Nerve Repair: Paul Brennan’s Big Idea That Might Change The World was originally published in Authority Magazine on Medium, where people are continuing the conversation by highlighting and responding to this story.