PERTH, Australia Australian stem cell therapy company Mesoblast Ltd. announced that the FDA gave it the green light to test its allogeneic mesenchymal stem cell (MSC) product candidate remestemcel-L in patients with acute respiratory distress syndrome (ARDS) caused by coronavirus (COVID-19).

Were going to be evaluating whether an injection of our cells intravenously can tone down the immune system just enough so it gets rid of the virus but doesnt destroy your lungs at the same time, Mesoblast CEO Silviu Itescu told BioWorld.

What people are dying of is acute respiratory distress syndrome, which is the bodys immune response to the virus in the lungs, and the immune system goes haywire, and in its battle with the virus it overreacts and causes severe damage to the lungs, Itescu said.

The FDA clearance provides a pathway in the United States for use of remestemcel-L in patients with COVID-19 ARDS, where the prognosis is very dismal, under both expanded access compassionate use and in a planned randomized controlled trial.

The company is in active discussions with various governments, regulatory authorities, medical institutions and pharmaceutical companies.

Recently published results from an investigator-initiated clinical study conducted in China reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients. A post-hoc analysis of a randomized, placebo-controlled study in 60 patients with chronic obstructive pulmonary disease demonstrated that remestemcel-L significantly improved respiratory function in patients with the same elevated inflammatory biomarkers that are also observed in patients with COVID-19 ARDS.

Remestemcel-L is being developed for various inflammatory conditions and is believed to counteract the inflammatory processes implicated in those diseases by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

The safety and therapeutic effects of remestemcel-L intravenous infusions have been evaluated in more than 1,100 patients in various clinical trials.

The stem cell therapy was successful in a phase III trial for steroid-refractory acute graft-vs.-host disease (aGVHD) in children, a potentially fatal inflammatory condition due to a similar cytokine storm process as is seen in COVID-19 ARDS.

Cynata in preclinical ARDs studies

Fellow Aussie regenerative medicine company Cynata Therapeutics Ltd. is studying the utility of its Cymerus MSCs as a treatment for ARDS associated with COVID-19 with the Critical Care Research Group at Prince Charles Hospital in Brisbane, Australia.

Acute respiratory distress syndrome is a huge problem worldwide and is prevalent aside from COVID-19, but suddenly it is on the front page because people are dying of this. The data behooves us to see if MSC treatment can rescue people from this, Cynata CEO Ross Macdonald told BioWorld.

The Critical Care Research Group has long seen the need to improve interventions in patients who have ARDS, and they have an interest in MSCs and came to us, he said.

ARDS is an inflammatory process leading to the build-up of fluid in the lungs and respiratory failure. It can occur due to infection, trauma and inhalation of noxious substances. ARDS often affects previously healthy individuals and accounts for roughly 10% of all ICU admissions, with almost 25% of patients requiring mechanical ventilation. Survivors of ARDS are often left with severe long-term illness and disability.

The study will investigate Cynatas Cymerus MSCs as a treatment for ARDS, in combination with extracorporeal membrane oxygenation (ECMO). ECMO circulates blood through an artificial lung, oxygenating the blood before putting it back into the bloodstream of a patient. ECMO has emerged as a treatment adjunct to support the vital organs in patients with severe ARDS, which can provide short- to medium-term mechanical pulmonary support.

MSC therapy could be used as a possible treatment for ARDS due to the ability of MSCs to reduce inflammation, enhance clearance of pathogens and stimulate tissue repair.

The study will first seek to determine if Cymerus MSC treatment improves oxygenation in sheep with ARDS supported by ECMO, and to evaluate the effects on lung mechanics, blood flow, inflammation and lung injury, as well as safety.

If the study is successful, the data would support progression to a clinical trial of Cymerus MSCs in humans with ARDS undergoing ECMO support.

The study is being funded by the Queensland State Government, the National Health and Medical Research Council (NHMRC), the Intensive Care Society UK, and the Prince Charles Hospital Foundation.

If the FDA or TGA wants us to step in, were all ears. Our product is manufactured in the United States, and supply is not an issue. In theory, were ready to go, Macdonald said.

He was quick to point out that what differentiates Cynatas stem cell product from competitors is that its MSCs are derived from induced pluripotent stem cells (iPSCs), and most stem cell companies rely on multiple donors to donate either bone marrow or adipose tissue as their primary tissue sources. From those sources they derive a small number of MSCs, which represent the starting material of their manufacturing process.

Cynatas Cymerus MSC therapy comes from a single donor and can be produced in limitless quantities, giving it the potential to create a new standard, Macdonald said. The platform technology is based on versatile stem cells known as mesenchymoangioblasts (MCAs), which are a precursor of mesenchymal stem cells.

That process allows the company to make MSCs derived from iPSCs in large amounts without losing their potency, and that forms the basis for the companys platform technology, which it calls Cymerus.

Cynata is gearing up for three phase II trials with its Cymerus MSCs in graft-vs.-host disease (GVHD), critical limb ischemia and osteoarthritis.

Mesoblasts remestemcel-L is being studied in clinical trials across several inflammatory conditions, including in elderly patients with lung disease and adults and children with steroid-refractory aGVHD, heart failure and chronic low back pain due to intervertebral disc degeneration.

The FDA recently accepted Mesoblasts BLA for priority review for remestemcel-L for children with aGVHD. It has a PDUFA date of Sept. 30 for the product branded as Ryoncil.

Mesoblast shares (ASX:MSB) were up nearly 34% to AU$1.78 from AU$1.32 per share by market close April 6.

Cynatas shares (ASX:CYP) were trading at AU86 cents on April 7.

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MSC-based therapies from Mesoblast, Cynata advance to tackle COVID-19 ARDS - BioWorld Online