Dr. Wise Young Speech

Hi, it's been a long time since I've talked to my friends at the Central Jersey Spinal Cord Association. I very much miss being with you. Let me go back to March of 2020. We did not start our clinical trial then when the COVID-19 pandemic swept New Jersey and New York. All the hospitals in the region stopped non-essential surgery and clinical trials. In August of 2020, StemSite, the sponsor of our trial, informed investigators in the trial that they were pulling out of the trial due to COVID-19. Two months later, they told me that they were going to move the trial to Taiwan. I told them that I would start a new trial with a company that I had started called Mononuclear Therapeutics. In November of 2020, the top three umbilical cord blood banks in the United States have all agreed to supply umbilical cord blood to us to do the trial. These include New York Blood Bank, which is the original and the best cord blood bank; Duke Carolinas Cord Blood Bank, headed by Joanne Kurtzberg; and the University of Colorado Cord Blood Bank. All three of these cord blood banks have approved biological license applications to treat patients with umbilical cord blood. In January of 2021, we tested blood from cord blood from all three centers. This clinical trial that we will do will be testing 40 patients with chronic complete spinal cord injury: 10 patients per cord blood center bank, and there will be 10 patients who will be controlled, non-treated controls. These 10 patients will not receive any cell transplants initially, but they will eventually at the end of one year receive the cord blood treatment, and they will then receive the walking program a second time. All the subjects will receive six months of intensive locomotor training, and the control untreated group will receive the cell transplants and have an additional six months beyond that. So all the subjects will not only be involved with the locomotor training, they actually will be assessed for a whole year after the transplants have been done. Every subject will eventually get transplant and intense locomotor training. We started to raise money for the new trial that was just in 2021, and due to the larger number of subjects, the trial will cost eight million dollars, which used to be about five million dollars for 27 patients. We're planning to use the same surgical centers: Mount Sinai East and West, Mountainside Hospital in Montclair, Hackensack Medical Center in Hackensack, and Hackensack Meridian Hospital in Neptune, New Jersey. The rehabilitation centers will be the same: Kessler, Mount Sinai, Hackensack, New Jersey Shore, JFK Medical Center, and the Good Shepherd in Allentown, Pennsylvania. After six months of rehabilitation, they will go to the walking centers such as Push to Walk and Project Walk, Mount Sinai, and the Good Shepherd. Those that recover minimally assisted walking will continue walking in new runway parks, thanks to the encouragement and help of the New Brunswick Parks. I mean Middlesex County, who oversees the New Brunswick parks. We're planning to submit the application for a clinical trial in September and hope to start the trial in early 2022. I sincerely apologize for these long delays. Mononuclear Therapeutics is raising the funds for these clinical trials, and we're working with the New York Blood Center to process the umbilical cord blood mononuclear cells for the clinical trials. The trial will require COVID-19 vaccination of all subjects and caretakers that have daily contact with the subjects. Hopefully, the timing of the trial will be such that the infection rate will be low by the time it starts. The trial should finish in 2023. At that time, we will go ahead and initiate a Phase 3 clinical trial around the world and to see if we can get global approval of the treatment. Since 2016-17, when we first started planning and implementing the trial, several major advances have occurred in the spinal cord injury field. We published our results in 2016, and since that time, over 1,000 papers have been published reporting positive results of cell transplant therapies in animal studies, and particularly the use of one type of cells called mesenchymal stem cells. Over 20 clinical trials have reported positive results of mesenchymal cell transplants in patients with subacute and chronic spinal cord injury. Most of them use mesenchymal stem cells from fat, adipose tissue, or bone marrow. However, none of the trials of mesenchymal stem cells published since 2016 involved HLA-matched umbilical cord blood mononuclear cells, which is what we used to treat our patients. None of them utilized intensive locomotor training after the transplantations or randomized controlled to show that the treatment really made a difference compared to non-treatment. Umbilical cord blood cells, in our opinion, are still the best cells for the following reasons. First, umbilical cord blood mononuclear cells contain mesenchymal stem cells, which is what everybody says is potentially beneficial. Second, umbilical cord blood cells contain monocytes, which make macrophages, and they produce neurotrophins that stimulate regeneration. Third, our results suggest that intense locomotor training after the transplants stimulates or induces locomotor recovery in the patients and also bowel and bladder function. We need a clinical trial to assess and confirm these results, and we are still very much need to establish these results and take it to Phase 3 clinical trials. In the meantime, we have developed the technology at Mononuclear Therapeutics to allow much more efficient collection and processing of umbilical cord blood that would allow the treatment of millions of people with spinal cord injury. In addition, we have developed a business model working with the best public cord blood banks around the world. For example, we're now working with New York Blood Bank, the University of Colorado, and Duke Carolinas Blood Bank to establish a model where we can go to the best cord blood banks to utilize their available stock of stored frozen umbilical cord blood. Many cord blood banks are very interested in working with us to utilize more cord blood and use the new and much more efficient methods that we've developed to collect and process cord blood. This method will allow us to treat up to 10 patients with one umbilical cord blood unit. We've also developed a way to treat brain and spinal cord injury with umbilical cord blood exosomes, which cross the blood-brain barrier and stimulate neurogenesis. Thus, for the first time, we can give umbilical cord blood exosomes to patients with lumbosacral and cervical spinal cord injury to stimulate neurogenesis, to create new neurons in the spinal cord. For the first time, we will be able to utilize the plasma of umbilical cord blood, which is now being thrown away at most of the umbilical cord blood banks. We discovered that umbilical cord blood plasma contains trillions of exosomes that cross the blood-brain barrier and the blood-spinal cord barrier to stimulate neurogenesis. Umbilical cord blood exosomes will provide ways to treat thoracic and cervical spinal cord injury, hypoxic ischemic stroke, Down syndrome and other causes of mental retardation, macular degeneration, and glaucoma. Animal studies are showing very promising results. In two years, we can start clinical trials of cord blood mononuclear cell transplants to regenerate the spinal cord and exosome therapy to stimulate neurogenesis at the same time. Finally, we're very anxious to initiate clinical trials of lithium to treat severe neuropathic pain in patients with spinal cord injury and peripheral nerve injuries. I believe we're entering a new era of neurotherapies that will make new neurons for the brain and spinal cord. The future is looking very bright for cervical and lumbosacral spinal cord injury, ischemia, traumatic brain injury, prevention and reversal of retinal degeneration, specifically macular degeneration, and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Our research at the Keck Center will lead the way from laboratory bench to clinical trial. I am deeply grateful to the Central Jersey Spinal Cord Injury Association for all your support, to all of you, and especially Kevin Hoakland for your wonderful support over these years. We would never be where we are without you. From everybody at the Keck Center, thank you so very much.