Plurisitem Therapeutics’ PLX (Placental eXpanded) cells are showing promise as a therapy for patients with severe cases of COVID-19.
Plurisitem Therapeutics’ PLX (Placental eXpanded) cells are showing promise as a therapy for patients with severe cases of COVID-19.
In severe cases of SARS-CoV-2 infections, the immune system has been hyper-activated, triggering a cytokine storm that may ultimately lead to organ failure.
PLX cells appear to modulate the cytokine storm, thus restabilizing the immune system and mitigating the tissue damage associated with acute respiratory distress syndrome (ARDS) that results from severe SARS-CoV-2 infections, said Racheli Ofir, Ph.D., VP, research & intellectual property, Pluristem. She spoke April 22 as part of the Global Cell & Gene Digital Week series of webinars.
Currently, Pluristem is treating patients in Israel and recently began treatment in the U.S. under compassionate use protocols. It simultaneously is working with regulators at the FDA and EMA to develop a multinational clinical trial for COVID-19.
Preliminary data from compassionate use treatments has not been published, but Ofir shared it during her presentation. Most importantly, the six patients with acute respiratory failure (meaning they required ventilators) treated in that program all survived. After one week, four of the six demonstrated respiratory improvement and three were in the advanced stages of being weaned from the ventilator.
Based on those results, on April 13 Pluristem expanded its compassionate use program and treated its first patient in the U.S. under the FDA’s Coronavirus Treatment Acceleration Program.
“PLX cells are an off-the-shelf product that is administered intramuscularly. Tissue- or genetic-matching are not required,” Ofir said. “The PLX cells were given to COVID-19 patients in addition to everything they were receiving. The standard of care was continued. We see no reason to believe there will be contraindications between PLX and other products.”
Phase III trials for other indications already are underway in the U.S., Europe and Israel, targeting critical limb ischemia and muscle regeneration following hip fracture. Other trials are progressing for acute radiation syndrome, intermittent claudication and graft versus host disease.
PLX cells have shown positive clinical data in response to inflammation, ischemia/reperfusion injury, muscle trauma, irradiation and hematological disorders. In animal models, PLX cells generated therapeutic effects in pulmonary hypertension, lung fibrosis, acute kidney injury and gastrointestinal injury.
Their immunomodulatory properties include generating regulatory T cells and M2 macrophages. Specifically, studies showed T regulator cells were stimulated and TH 1 cells were inhibited. PLX increased the expression of the M2 marker CD209 and decreased the expression of the M1 markers. Each of these might reduce the deadly symptoms of pneumonia and pneumonitis, caused by the COVID-19. Studies also showed PLX cells inhibited the proliferation of PHA-stimulated PBMCs and increased IL-10 secretion.
The cells also can activate natural killer (NK) cells and possibly CD8+ T cells. Both cell populations are important in killing viral-infected cells. In the case of COVID-19, the cells boost immunological intratissue virus control.
“PLX cells are capable of a large variety of activities,” she underscored, “including forming new blood vessels, reducing oxidative stress, and secreting factors for muscle regeneration.”
With these capabilities, their value in treating severe cases of COVID-19 appears promising.
PLX cells’ mechanism of action is secretion. They modulate undesired inflammation and direct regeneration capabilities. As Ofir explained, “The cells are injected into the muscle near the target organ and begin to secrete factors that are transferred systemically to the areas of the body where healing is needed.
“What’s particularly interesting is that they are smart cells,” she continued. “They respond to their environment, changing their secretions in response to the disease of the patients. After about two weeks, they clear the system.”
“The cells are very sensitive to their environment,” Ofir said. Altering the conditions of the bioreactor allows them to be fine-tuned to treat differing conditions. “Different cultures give rise to different cell populations.”
Pluristem, therefore, has developed two types of PLX cells: PLX-PAD for immunomodulation and muscle regeneration, and PLX-R18 to regulate the hemopoietic system and regenerate bone marrow. PLX-PAD is the version best-suited to treat COVID-19.
“We don’t actively select cells, but we can change the cells’ characteristics by changing the cell culture parameters. Controlling manufacturing is the key factor for success of the product,” she said.
PLX cells are derived from the placentas of young, healthy donors who have C-sections (after informed consent). Placentas provide an ethical source of cells, and they are readily available and in virtually unlimited supply. “One placenta can produce 20,000 doses.”
That ready supply, coupled with a well-developed, highly scalable manufacturing capability and logistics infrastructure are competitive advantages.
“We have a lot of capacity in Israel and already have large quantities of cells distributed in the U.S. and Europe,” she said. That’s another advantage, enabling rapid distribution once the cells are approved for broader use. Shelf life is four years and counting.
