Author: Greta Gohring (Research Assistant, Organicell Regenerative Medicine)
Regenerative Medicine is a rapidly expanding sector of biotechnology with numerous innovative therapeutics. Regenerative medicine encompasses a multitude of specialties such as orthopedics, immunology, and cardiology, while following common trends within the fields of tissue and cell engineering. In contrast to common symptom-targeting therapeutics, which temporarily relieve and subdue conditions, regenerative medicine is designed to reprogram damaged or diseased tissues back to a healthy state. Through reprogramming, regenerative medicine has the potential to provide long-term effects in chronic and reoccurring symptomatic diseases.
Stem cell and other cell-based therapies have proven to be strong therapeutic candidates for many regenerative and tissue restorative applications. However, complications with post transplantation viability, clinical reproducibility, and large-scale development have stalled these products in the path to drug approval.
In an effort to enhance and build from the lessons learned in cell-based research and clinical trials, researchers have begun to shift focus to cell-to-cell secreted factors such as extracellular vesicles. Extracellular vesicles, secreted from the cell membrane or the cell’s internal recycling pathways, carry many of the same molecular messengers and factors found to be therapeutic in cell therapies.
Therefore, through the development of technologies to isolate extracellular vesicles from sources such as cell cultures and biologic fluids, extracellular vesicle-based therapies have begun to take center stage in regenerative medicine clinical applications.
Therapeutic Potential of Exosomes
Exosomes are a subtype of extracellular vesicles derived from the cell’s recycling pathway, specifically the endosome. During exosome formation, small nucleic acids, enzymes, and other molecular mediators are packaged into lipid membranes and secreted out of the cells. These exosomes are then absorbed by surrounding cells as a form of cell-to-cell communication.
The absorption of exosomes into various cell types can lead to modifications in gene expression, cell metabolism, and other signaling pathways. Depending on the cell of origin, exosomes have been linked to regenerative effects via the suppression of pro-inflammatory response and immune activation, as well as the promotion of cell proliferation and enhancement of tissue wound healing.
Technologies have enabled researchers to isolate and characterize exosomes derived from a single cell source or from naturally occurring biologic fluids such as amniotic fluid and whole blood. While much of the pre-clinical development of exosome-based therapies has focused on a single cell sourced methodology, it has been found that the collection of extracellular vesicle rich biological fluids may supersede the need to manufacture in vitro cultured products and may surpass associated challenges of cell manufacturing and qualification.
Organicell Regenerative Medicine, Inc. (OTCQB:OCEL) is a clinical-stage biopharmaceutical company that harnesses the power of extracellular vesicles and exosomes to develop innovative biological therapeutics for the treatment of degenerative diseases. Organicell’s lead product, Zofin™, is an acellular biologic therapeutic derived from perinatal sources. Zofin™ is manufactured to retain naturally occurring exosomes, hyaluronic acid, proteins, and microRNAs, without the addition or combination of any other substance or diluent.
MicroRNAs (miRNA) are a type of small, non-coding RNA that play an important role in gene expression. As one of the largest RNA components packaged into exosomes, the delivery of miRNA into a cell can lead to long term changes in gene expression and protein production. miRNAs are thought to be the key component in Zofin™, as they have been found to target an array of inflammatory genes, providing an anti-inflammatory and immunomodulatory effect.
Extracellular Vesicle Therapeutics in the Clinic
Extracellular vesicle therapies, which includes exosomes, are currently entering phase I/II clinical trials. Organicell Regenerative Medicine is amongst the first groups of innovators to spearhead the use of naturally occurring extracellular vesicles as a next-generation therapeutic tool for inflammatory and chronic disease.
Organicell’s lead therapeutic Zofin™, has received FDA approval for 18 eINDs (Emergency Investigational New Drug Applications), four Phase I/II randomized, placebo-controlled trials investigating the therapeutic potential of Zofin™ for COVID-19, Chronic Obstructive Pulmonary Disease (COPD), Osteoarthritis (OA), and COVID Long Haulers, as well as an Expanded Access trial which was completed and published in December 2021 for Mild to Moderate COVID-19.
To date, there has not been a severe adverse event that has been reported to be associated with the use of Zofin™.
A summary of Organicell’s clinical development to date includes:
1. Moderate to Severe COVID-19
A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin™ for the Treatment of Moderate to Severe Acute Respiratory Syndrome (SARS) Related to COVID-19 Infection vs Placebo. The clinical trial is currently in process. A total of ten patients have been enrolled to the study thus far and currently the clinical trial is not enrolling subjects due to the challenges of enrolling the remaining study population.
2. Chronic Obstructive Pulmonary Disease (COPD)
A Phase I/II Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin™ for the Treatment of patients diagnosed with chronic obstructive pulmonary disease (COPD). Trial enrollment expected to begin during the first quarter of 2022.
A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Zofin™ Infused Intravenously in Patients Suffering with Knee Osteoarthritis vs Placebo. Trial initiation expected to begin during the end of the second quarter of 2022.
4. COVID Long Haulers
A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin™ for the Treatment of Post COVID-19 Complications “Long Haulers” vs Placebo. Trial has begun and is underway.
Therapeutic Efficacy of Zofin™ and COVID-19
The demonstration of safety and efficacy of extracellular-based therapeutics is a crucial first step in new drug development. Organicell’s program to investigate the therapeutic potential of Zofin™ and COVID-19 is to test the hypothesis that Zofin™ may be beneficial as an anti-inflammatory and immune modulatory therapeutic.
Under expanded access, Zofin™ has been administered to patients with mild to moderate COVID-19 infection. Analysis of patient outcomes, including COVID-19-associated symptoms, chest x-ray images, and inflammatory biomarkers demonstrated the beneficial outcomes that may indicate Zofin’s efficacy and therapeutic value for preventing disease progression. Evidence supports Zofin’s ability to prevent disease progression for this generalized cohort of mild-to-moderate COVID-19 patients—especially those with a high-risk factor of obesity.
The completed study supports Zofin as a feasible, safe, and potentially efficacious therapy for patients with mild-to-moderate COVID-19 who are at increased risk for progression, including the need for hospitalization, ventilation, and death.
Furthermore, in a single-patient case report study, Zofin™ was administered to a single long hauler patient experiencing prolonged shortness of breath and respiratory impairment. Analysis of patient outcomes, including chest x-ray images, biomarkers, and prolonged COVID-19-associated symptoms, demonstrated the beneficial outcomes that may indicate Zofin’s efficacy and therapeutic value for recovering from prolonged COVID symptoms induced by COVID-19 infection. By the conclusion of the study period, the patient had returned to normal with no observation of impairments or respiratory distress.
These studies demonstrate the first use of human amniotic fluid-derived extracellular vesicles and soluble factors as a safe and potentially efficacious therapeutic treatment for acute respiratory distress syndrome induced by COVID-19 infection and for the recovery from long hauler complications induced by COVID-19 infection. The intravenous and multi-dose administration of Zofin™ was found to be safe and well tolerated without the report of any serious adverse events.