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Pulmostem™ is targeting lung diseases

Amniotics lead drug candidate Pulmostem™ is targeting lung diseases where fibrosis and inflammation are key components. These diseases include Acute Respiratory Distress Syndrome (ARDS), Idiopathic Pulmonary Fibrosis (IPF) and acute transplant rejection associated with lung transplantation.

ARDS and COVID-19 triggered ARDS – acute inflammation and acute fibrosis

Acute respiratory distress syndrome, ARDS is characterized by an acute inflammatory condition with respiratory failure (lung dysfunction) and bilateral pulmonary edema associated with hypoxia. When lung dysfunction is caused by severe infection or multi-trauma, there is usually also a massive tissue damage and greatly increased proinflammatory response. This results in acute lung barrier damage and a disturbed gas exchange in the lung leading to acute respiratory problems. Patients with ARDS are intensively cared for, but still have a high mortality rate.

The new coronavirus disease (COVID-19) has grown into a global public health crisis where the most serious cases develop ARDS. Of the COVID-19 patients who develop symptoms, most recover, but some become critically ill and require intensive care. There is also a large chronic morbidity in the aftermath, up to 10%, even after moderate illness.

Respiratory problems caused by COVID-19 have a complex development, which is today incompletely known. In the early stages of the disease, antiviral therapy may be effective, while in the later stages of the infection in severe cases, the virus titer will not be high, and the complications are instead due to a harmful elevated inflammatory response in the patient. One hypothesis is therefore that down-regulation or avoidance of cytokine storms may be the key to treating severe COVID-19. The severity of lung damage correlates with the extent of pulmonary infiltration of inflammatory cells. It is also clear that survivors recovering from a severe coronavirus infection may have signs of lung damage several months later.

Current therapies

There are currently no effective therapies that prevent or cure ARDS. There is also no drug with adequate effect against ARDS triggered by COVID-19. Traditional corticosteroids are recommended for the treatment of patients with severe and critical COVID-19. Remdesivir, an antiviral drug, was approved in 2020 by EU and US health authorities. Recently, research has shown that Remdesivir provides only a modest improvement for patients. In addition to this, there are a large number of treatments within different stages of experimental and clinical evaluation.

Idiopathic pulmonary fibrosis – chronic inflammation and chronic fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic and irreversible fatal lung disease characterized by chronic inflammation and fibrosis, which makes the lung increasingly stiffer with impaired gas exchange as a result. Only two treatment options are available on the market. Both of these options are associated with troublesome side effects, which makes it difficult for many of the patients to maintain their long-term treatment.

Mortality in IPF is high, with a reported median survival of 2–3 years from diagnosis and approximately 20 percent survival at five years after diagnosis. IPF is a relatively rare disease, but due to its severity it is a significant burden on society. Every year, 14 percent of IPF patients have an acute exacerbation event, which is characterized by a sudden deterioration which may require respiratory care in the intensive care unit. Available data indicate that 46 percent of those who die in the patient group are diagnosed with idiopathic pulmonary fibrosis who have had an acute exacerbation. The median survival time from acute exacerbation is three to four months.

Current therapies

The treatment options for IPF are limited, with only two therapies approved for IPF in the world today. These are the antifibrotic drugs, Ofev (Nintedanib, Boehringer Ingelheim) and Esbriet (Pirfenidone, Genentech), both of which are disease-modifying drugs that delay the development of the disease but do not cure the disease or prevent progression. In addition, both therapies lead to troublesome gastrointestinal side effects (eg nausea, vomiting and diarrhea) which in many cases prevent further medication. Other negative side effects are such as liver damage, and in terms of Esbriet rash and photosensitivity. Taken together, the tolerability profiles limit the patient population that can be effectively treated with these therapies.

Lung transplantation can be a life-saving treatment, but is associated with Primary Graft Dysfunction (PGD) to a relatively high degree and lack of suitable lungs. All in all, there is a clear and distinct need for new forms of treatment for IPF that can stop, or at best reverse, the development of the disease and improve the currently gloomy prognosis.

Lung transplantation / Primary graft dysfunction

Lung transplantation (LT) has become an increasingly common procedure, however, the procedure has consistently lagged behind other organ transplants for survival. Primary Graft Dysfunction (PGD) is a severe form of acute shock lung that is primarily related to ischemia-reperfusion injury with failing function of the transplanted lung. About 12 percent to 55 percent of lung transplant patients, depending on when organ function is monitored, experience this type of complication. The complication is associated with significantly increased morbidity and mortality and poorer function of the transplanted lung. Patients undergoing a lung transplant are treated with a respirator to relieve the symptoms associated with secondary shock lung (ARDS). There is currently no safe treatment to prevent PGD in connection with lung transplantation.