The Food and Drug Administration is expected to approve the first of a whole new type of weapon to be tested in the international struggle against COVID-19 as the disease continues to sweep across the globe.
New Jersey-based therapeutics company Celularity announced that its cancer treatment, CYNK-001, is awaiting "investigational new drug" status for COVID-19 from the FDA, which could come any day. Once the treatment gets the status, it will immediately enter a preliminary clinical trial to see if it can help people suffering from the illness.Independent immunologists say the rationale for the treatment is solid but warn that it could exacerbate the most severe cases of the disease. If the new strategy proves effective, Celularity stands ready to rapidly increase production.
"It's important the world knows that there are companies out there developing therapies," said Dr. Robert Hariri, Celularity's founder, chairman and CEO. "I bet we will have a therapy."
Celularity — which has raised $311 million in venture capital funding and attracted the support of big-name entrepreneurs like John Sculley, former CEO of Pepsi and Apple — is a growing biotech company with dreams of taking stem cell therapies mainstream. While sourcing these flexible cells has traditionally been ethically controversial, Hariri, a biomedical researcher, has developed a way to grow the regenerative cells from human placentas which would otherwise be thrown away.
Sculley, the vice chair of the company's board of directors, envisions a wide range of applications, including someday growing synthetic lungs, but one of the company's initial goals has been to make a cutting-edge cancer treatment more accessible. Infusions of a certain type of immune cell known as Natural Killer (NK) cells have proven effective in some cases. "All of a sudden their cancer starts melting way," says Corey Casper, a medical researcher and president of the Infectious Disease Research Institute in Seattle. "It's like science fiction."
But creating personalized NK cells from a patient's blood is a laborious and lengthy process, which is why Celularity developed CYNK-001. The company transforms placental stem cells into one-size-fits all NK cells, which they keep on ice, ready for transfusion into any patient, at any time. "What's really a game changer here is these end cells can be stored on the shelf and are ready, not specific to any one individual," says Casper. "It's a leap in the technology we haven't had before."
Now Celularity is hoping that its NK cells might help patients suffering from COVID-19 too. Where many of the drugs currently under investigation try to neutralize the SARS-CoV-2 virus directly, CYNK-001 — which is the first cell therapy awaiting FDA approval for trials for this illness — has a different goal: to deliver reinforcements to a beleaguered immune system.
When a virus invades the body, the immune system produces a horde of specialized cells that hunt down and kill the intruders. But learning to recognize the virus and raising an army takes days to a week. During that time, NK cells act as sentinels and keep the virus from replicating out of control. How exactly they pull off this task isn't completely understood, but one of their abilities is to target and destroy stressed cells — a potential sign of infection.
This general capacity to target any and all diseased cells is what makes NK cells effective against certain cancers, and it also makes them the body's first line of defense against viruses of all varieties. Celularity hopes that additional NK cells will curb SARS-CoV-2's ability to spread through the body, buying enough time for the immune system to start producing its own antibodies and permanently quell the infection.
But will it work? Some research suggests that transplanting mature NK cells into baby mice makes them less susceptible to one particular virus, but no researcher has yet succeeded in using the all-purpose fighters to defeat a virus in humans. One challenge is that viruses and NK cells are ancient foes, and many viruses have become skilled in deception over the eons. "We kind of get hoodwinked by the virus' ability to evade the NK cells," says Wayne Yokoyama, an immunologist at the Washington University School of Medicine in St. Louis and longtime researcher of NK cells.
Yokoyama calls the CYNK-001 treatment "an intriguing idea," but says that the only way to discover whether SARS-CoV-2 will prove a stealth master or a sitting duck is to try and see.
He warns, however, that testing should proceed with extreme caution. COVID-19 turns lethal when the immune system goes on a rampage in what's known as a "cytokine storm," recklessly attacking otherwise healthy lung cells. For these people, pushing the immune system even further into overdrive with additional NK cells is the last thing doctors want to do.
Celularity has proved CYNK-001 safe in small numbers of cancer patients, but in those cases the immune system generally remains calm, at little risk of being pushed over the edge. it has been used as a treatment for acute myeloid leukemia, multiple myeloma, and glioblastoma multiforme. "Findings in cancer patients cannot be transposed to COVID-19 patients," says Puck van Kasteren, a virologist at the National Institute for Public Health in the Netherlands.
But Dr. Hariri notes that the immune system does sometimes respond strongly while fighting cancer, and that Celularity has not observed any signs of cytokine storms while treating cancer patients with CYNK-001. He does not expect that CYNK-001 will cause any adverse effects in COVID-19 patients either. "Although this viral disease is different, we have taken steps to design our clinical trial to "tune" the anti-viral effect by escalating dose slowly while monitoring for evidence of toxicity," says Dr. Hariri.
He notes that there is early evidence this treatment holds promise. The National Research Project for SARS, Beijing Group has studied NK cell number and function in patients of severe acute respiratory syndrome and the findings point to the fact that they play a direct role in fighting coronavirus.
With the FDA's blessing, Casper will immediately begin recruiting 86 patients for a combined Phase I/Phase II clinical trial to test whether CYNK-001 is safe and effective for patients with COVID-19. The full trial will last for 11 months from recruitment to analysis, but he hopes the treatment's effects will become visible within weeks to months. Celularity is funding the trial, which will cost millions of dollars.
To minimize the risk of patients succumbing to what Casper calls "friendly fire" from a rampaging immune system, the trial will focus on moderately ill people — patients who are hospitalized but not those who already need intensive care. Doctors will monitor the first 14 patients especially closely for any signs that CYNK-001 is triggering cytokine storms. "This is a new therapy, and safety comes first," Casper says. "If we see any signal, we will stop immediately. My hope is that we won't see this."
The therapy will join hundreds of other treatments currently undergoing FDA-approved testing for Covid-19. Statistically speaking, about one-third of such experimental drugs advance to Phase III for large-scale, rigorous testing.
If CYNK-001 is among the effective treatments, Celularity will be ready to ramp up production quickly. It can derive about 1,000 stem cells from a single placenta. The company recently built a $75 million factory in New Jersey and anticipates being able to produce tens to hundreds of thousands of treatments by summer, according to Sculley. "This is not a dream of the future," he says.
Early price projections put CYNK-001 at between $2,000 and $7,000 per dose, and in the clinical trial, each patient will receive three doses over the course of one week. But a Celularity spokesperson said that it's too early to know what the treatment might cost if it reaches the market.
And if NK cells aren't able to bring the SARS-CoV-2 virus to heel, that lesson could be useful to researchers, too. In the global war against COVID-19, every battle helps turn the tide. "You've got to start somewhere," Yokoyama says. "Maybe this in itself gives us some valuable clues as to what the next step might be."