MSCs demonstrate efficacy in preclinical lung disease study

MELBOURNE—Cynata Therapeutics Ltd., a clinical-stage biotechnology company specializing in cell therapeutics, recently announced positive efficacy data from a study of its induced pluripotent stem cell (iPSC)-derived Cymerus mesenchymal stem cells (MSCs) in a preclinical rodent model of idiopathic pulmonary fibrosis (IPF).

IPF is a currently incurable disease of unknown cause, which results in extensive scarring or fibrosis of the lungs. Lung damage is often advanced by the time the condition is initially diagnosed, and existing treatment options have very limited efficacy. It invariably progresses to respiratory failure, with only 20 to 30 percent of patients surviving five years from the time of diagnosis. The value of the global IPF market is expected to reach around $5.9 billion by 2025, with an annual growth of 13 percent.

“These latest results with Cymerus MSCs add to the large body of evidence on the potency of these cells and their potential utility in treating a wide range of devastating diseases,” said Dr. Kilian Kelly, chief operating officer of Cynata. “IPF represents an enormous unmet medical need, as existing treatment options have only modest effects on disease progression and survival rates.”

It is notable that fibrosis is observed in the lungs of COVID-19 patients with severe disease and may become an important factor in the longer-term effects in such surviving patients, the company notes. It also occurs in surviving patients of acute respiratory distress syndrome from other causes. As previously announced, Cynata is conducting a Phase 2 clinical trial in patients with respiratory distress associated with COVID19.

The effect of Cymerus MSCs is being studied in the widely used and clinically relevant bleomycin-induced IPF model, which is the gold-standard preclinical model of this condition, according to Cynata. Compared to placebo, the Cymerus MSC treatment led to statistically significant improvements in:

• Dynamic lung compliance (the lung’s ability to stretch and expand)
• Airway resistance (a measure of the airway’s opposition to airflow into the lungs)
• Interstitial lung inflammation (swelling in the tissue surrounding the airways)
• Interstitial lung fibrosis (fibrosis in the tissue surrounding the airways)
• Epithelial and subepithelial thickness (additional signs of fibrosis)

The initial phase of the IPF preclinical study found that control animals suffered a 40-percent loss of dynamic lung compliance after bleomycin administration, as expected in this model. However, when Cymerus MSC treatment was administered in a single dose three weeks later, or as a double dose at three and four weeks later, the loss of dynamic lung compliance was just 15 percent. Similarly, while bleomycin administration led to profound interstitial inflammation and fibrosis, as well as increases in airway resistance, epithelial thickness and subepithelial thickness, Cymerus MSC treatment dramatically reduced each of these harmful effects.

The study is led by Prof. Chrishan Samuel of the Department of Pharmacology at Monash University, following on from his previous studies which demonstrated that Cymerus MSCs significantly reduce fibrosis and inflammation in a model of asthma.

Commented Samuel: “These results are extremely encouraging. While they are very consistent with our previous studies of these cells in a model of asthma, it was important to confirm that the potent anti-inflammatory and anti-fibrotic effects of Cymerus MSCs would be replicated in IPF, which is a disease with very different underlying pathophysiology. We look forward to publishing our results in a peer-reviewed journal in due course.”