Major funding, totaling 1.49 million dollars, for pioneering research to treat Parkinson's disease, was secured from the Michael J. Fox Foundation, by the Greek-American-owned pharmaceutical company Kannalife.
In particular, the owners of Kannalife, Thoma Kikis and Dean Petkanas, presented the preclinical research project of the therapeutic KLS-13019, investigating its effect on neuroinflammation and mitochondrial dysfunction, which are involved in the disease of Parkinson's disease (PD).
In light of these news New Greek TV reached out to Dean Petkanas, CEO of Kannalife Sciences and asked a few questions about the company, it’s vision, ana its prospects.
How did Kannalife come about?
In 2007, Thoma Kikis began researching alternative therapies for his cousin, Dr. Steven Kazianis, a distinguished melanoma cancer researcher who was struggling with an anaplastic astrocytoma and undergone ineffective radiation and chemotherapy. Thoma delved into cannabis and cannabinoid research, focusing on the work of Dr. Cristina Sanchez from the University of Madrid a respected researcher from the 1990s centered on cannabinoids and cell cancer apoptosis. He read several of her papers, including “Cannabinoids and Gliomas” (2007), “Hypothesis: Cannabinoid Therapy for the Treatment of Gliomas” (2004), and “Anti-tumoral Action of Cannabinoids in Malignant Gliomas” (2003).
After presenting his findings to Dr. Kazianis, his cousin encouraged him to further validate the research if he believed it could actually become a drug for human use. Sadly, Dr. Kazianis who had been Thoma’s mentor early in life in the areas of music and photography, succumbed to the brain cancer six months later in 2008. Around the same time, Thoma’s father was diagnosed with liver cirrhosis.
In late 2008, during a visit to Los Angeles, Thoma was introduced to the emerging medical cannabis industry through multiple trips to the West Coast and considered the potential of this new market. He began the process of formulating ideas for a startup in the medical cannabis industry.
Thoma was familiar with my involvement with the biopharmaceutical startup Xechem, which successfully synthesized paclitaxel, an anti-cancer wonder drug the 1990s originally derived from the bark of the pacific yew tree. Thoma called me in March 2009 to discuss his desire to create a startup in the field of medical cannabis.
My answer was absolutely not. Partially for personal reasons as another start up at this time in my life would be very difficult on many fronts. By April 2010, after a great deal of insistence and persistence on Thoma's part, I relented to put a business plan together for a startup pharmaceutical company, however it would not involve cannabis, per se.
It would, however, involve looking at the active chemical ingredients in cannabis, namely cannabidiol or CBD and either developing or acquiring intellectual property. Since acquiring intellectual property might be possible, we looked at licensing a patent from the National Institutes of Health (NIH) to research cannabinoids as antioxidants and neuroprotectants. This was known as the '507 patent. We were the only company to ever license this technology from the U.S. Government. It gave us some ideas. We first studied CBD in the lab as a neuroprotectant for potential in treating / preventing the neurocognitive decay seen in a disease called overt hepatic encephalopathy (OHE).
By the end of 2013, we realized there were significant shortcomings in the chemistry and pharmacology of CBD and that it would be very difficult to get CBD through the FDA for diseases other than epilepsy or refractory disease states, where CBD could be the only answer. In late 2013 our medicinal chemistry team in Doylestown, PA, led by William Kinney and Mark McDonnell, embarked on creating a new class of compounds that attempted to improve on CBD's chemistry, and remove its shortcomings. By 2015 we had a nice patent estate of neuroprotective and anti-inflammatory compounds led by KLS- 13019. The rest is history to this point.
Was it a plan long in the making, or was it an intuitive leap?
It was faith and persistence. I never wanted to be in the medical cannabis industry, and today, true to form, we are not in the medical cannabis industry. We are in a field we helped to pioneer, targeted synthetic cannabinoid therapeutics. So, from the outset, here is where Thoma and I had a difference of opinion. I made it clear to him that the only real bridge that could ever be built to bring cannabinoid therapeutics into the field of ethical pharmaceuticals was the synthetic route. Nature gives you just so much, and in many instances, just so much is enough. But when nature is not enough, then science and technology must take over. The records and literature are replete with how nature gives way to synthetic analogues and compounds that take what nature gives and perfect it for clinical use. So from 2009 to 2010, I remained steadfast in my antipathy of starting a business in the medical marijuana space, which included among other things, the need for a controlled substance license, a knowledge of cultivation and botany, and living in a state where the regulatory environment was changing in favor of the "medical cannabis" use concept. Here is where God and faith enter the equation alongside persistence. Thoma was very persistent and relentless in wanting my involvement.
Yet every time I refused, his insistence for my involvement was like chipping away at a granite block. Eventually, in February 2010, I told Thoma I would pray over this situation and ask God for guidance. When we speak with God, it must be pure. It must be true. We must not speak with ourselves and just hear our words reverberate in our mind and look to settle like a ball on a roulette wheel. I waited for a response and the rhema (ῥῆμα) was stunning. Pure conviction. God asked me, "Haven't you been involved in a natural based anti-cancer compound that was ultimately synthesized?" I answered, “Absolutely.” I said. This was work I did for a startup pharmaceutical company called Xechem in 1992.” Then I asked a bold question, "Lord, if I set out to do this very difficult thing of a startup pharmaceutical company with no capital to start, I am willing to go through the trials, but how will the obstacles be removed." God answered, "Whenever you reach this point, don't quit, call on my name and remind me of this promise, the Lord your God will remove the obstacle." Overall, we are tasked to come up with a purpose. It is partly a plan, but it is mostly faith and believing the words spoken by Christ, in Matthew 19:26, "With man, this is impossible, but with God all things are possible." We believe in ourselves and in the strength that God has given us to persist in the face of significant obstacles. It should not be lost on our people that as Hellenic Christians, we are keepers of the faith the foundation of the first churches after the Resurrection.
When you first started out, did you have a specific vision, a targeted application that you were aiming for? For example, how did you decide to pursue this latest path you are on that landed you this support from The Michael J. Fox Foundation?
It is important to note the road less traveled as our success in the magnificent honor of being granted and award to study Parkinson’s Disease from The Michael J. Fox Foundation.
Where did it all start? How is it all connected?
The first targeted application was part of the rhema (ῥῆμα) I just spoke about. After this experience, I called Thoma and said, "Ok, let's do this, but you must follow my lead and we are going to start a pharmaceutical company.” Because of the specialized newly emerging field of cannabinoid therapeutics, which our company is a pioneer, I would need to hit the books and at least six to eight weeks of research to see how a plan can be developed around a specific disease. We would also need to build a body of technology and where I researched the opportunity for a license since we had no IP of our own at the start. After two months of heavy research and planning, I called Thoma and told him I had an executable business plan with the pharmaceutical side of the plan centered on potentially using cannabidiol (CBD) as a treatment for hepatic encephalopathy.
Thoma did not answer. I found it curious since he was relentless for a full year, insisting I put something together with him. When I asked if he knew what hepatic encephalopathy was, he told me that his father suffers from the disease. We knew at that moment that we had a defined purpose. We studied hepatic encephalopathy through 2016 with CBD and then our lead compound KLS-13019 and our preclinical results were very promising, but we were cash poor and needed to access grant funding in 2016 to continue this research in overt hepatic encephalopathy (OHE). Unfortunately, we did not score any grant money for OHE. However, in early 2017 we were invited to join Temple University in another grant application to perform preclinical animal studies our lead compound KLS-13019 against CBD and morphine in the treatment of chemotherapy induced peripheral neuropathy (CIPN). In late 2017 we received a phase 1 STTR grant award from the NIH to start the work.
By 2019 at the completion of this phase 1 study, the results were so promising, that we were able to obtain a $2.97 million three-year phase 2 STTR study grant in 2021.
We are now about one year away from first-in-human clinical trials with a drug that has the potential to prevent and reverse peripheral neuropathy brought on by paclitaxel. How ironic. I'm back where I started in 1992. God has an amazing sense of humor and irony.
It is from our early studies in OHE and the advancements we have made from 2017 to 2024 in CIPN that we were able to put a body of science together to obtain the attention of key personnel at The Michael J. Fox Foundation. That inquiry came from them in June 2021 and was a three-year journey and a wonderful story of its own. Perhaps one might say we have been on a Homeric Odyssey. Thankfully God has taken out the obstacles, and there were quite a few. Thankfully we’ve stayed the course.
Speaking on this latest award, can you elaborate a bit on what the research you are doing entails, and how it will further the fight against this very prevalent debilitating disease?
We are governed by strict confidentiality as to the details of the study protocol. We have outstanding research partners in Douglas Brenneman, PhD of Kannalife; Prof. Dr. Med. Chi Wang IP of Universitätsklinikum Würzburg; Tom H. Johnston, PdD of Atuka, Inc.; and James P. Koprich, MA, PhD - all who have put an outstanding study protocol together for our research program in Parkinson's. The working hypothesis is centered around mitochondrial dysfunction and inflammation. The potential posited by our science is that we have a drug that has been shown in animal studies to be an excellent neuroprotectant, and excellent anti-inflammatory at the same time, with dual molecular target efficiencies active in the mitochondria.
How were you chosen by the Foundation?
Again, we can't say this enough. Immense credit is due to the great people and scientists at The Michael J. Fox Foundation for recognizing an important scientific paper we published in 2019 on sodium-calcium regulation in the mitochondria. At that time we were focused on neuro-inflammation and how it can cause peripheral neuropathy.
It made us think outside the box and say, "What if..." Like I said before, God knows all things. We must be good stewards and servants to His will and purpose.
On a more Greek related theme, as scientists with a Greek heritage, how has your background helped you, if it has in your scientific quest.
The halls of science are filled with so many amazing Hellenic pioneers. We have been fortunate to meet several of them including the venerated Dr. George Yancopoulos, also a fellow Kastorian. Additionally our Hellenic friends who have recently offered their unselfish time, guidance and advice John Psaltos, Aris Despo, and Dr. Sotirios Stergiopoulos.
Of course, we would be remiss not to recognize the significant contributions of the great Dr. Roy Vagelos, and Dr. Stelios Papadopoulos, both icons of big pharma. While there are too many others to mention here, it is important to note the tremendous contributions by the Hellenic community in life sciences from time in memoriam. We have an incredible lineage dating back thousands of years. Perhaps one of the most important factors in assessing their contribution to our success at Kannalife is simply providing us with the culturally significant inspiration to be a part of this amazing roster of Hellenic contributors to the life sciences community. We are truly blessed.
