Our Research Focus
ONSPIRA THERAPEUTICS is focused on the development of life-changing medicines to bring hope to patients suffering from rare pulmonary diseases. Our lead program is a novel, inhaled interleukin-1 alpha & beta (IL-1 𝛼 & β) receptor antagonist protein being advanced for the treatment of bronchiolitis obliterans syndrome (BOS) in post-lung transplant patients.
IL-1 plays a key role in chronic inflammation and fibrosis in the lung.
VICIOUS CYCLE OF INFECTION, INFLAMMATION, OBSTRUCTION AND FIBROSIS
Through animal models and human clinical data, IL-1 𝛼 & β has been shown to be a critical mediator of chronic lung inflammation and fibrosis. An IL-1 𝛼 & β dependent positive feedback mechanism recruits polymorphonuclear leukocytes (PMNs) that express more IL-1 𝛼 & β and further drive inflammation and fibrosis. This vicious pathogenic cycle leads to a progressive increase in pulmonary fibrosis resulting in progressive loss of pulmonary function.
Inhibition of IL-1 mediated inflammation has the potential to beneficially impact each
phase of this cycle of progressive pulmonary disease.
No safe and effective therapies currently target the underlying combination of inflammation, remodeling/fibrosis, mucous over-production and loss of lung function in pulmonary conditions such as BOS and idiopathic pulmonary fibrosis (IPF).
Bronchiolitis Obliterans Syndrome
Bronchiolitis obliterans syndrome (BOS) is an inflammatory condition in which the bronchioles become obstructed. It is a form of chronic rejection that often follows lung transplant, other organ transplants and hematopoietic stem cell transplantation. It can also be caused by exposure to certain chemicals.
Incidence of OB/BOS Post Transplant
Approximately 50 percent of patients who receive a lung transplant develop BOS within five years of their transplant. This increases to more than 75 percent at 10 years. Based on the natural progression of disease, BOS is generally considered to be a progressive disease with low five year survival rates. BOS is the leading cause of morbidity and mortality in the pulmonary transplant population.
Adult Lung Transplants
Freedom from Bronchiolitis Obliterans Syndrome by Transplant Type Conditional
on Survival to 14 days
(Follow-ups: April 1994 – June 2014)
JHLT. 2015 Oct; 34(10): 1264-1277
Current treatments, none of which have been FDA approved for BOS, aim to slow progression but tend not to halt or reverse the inflammation. Unfortunately, many patients continue to decline and end up listed for re-transplant.
There is a significant need for a treatment to improve lung function and survival for patients post lung transplant. This would not only improve and extend the lives of these patients but would also in turn maximize the utility of the donor lungs, which are a scarce medical resource.
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible and usually lethal lung disease characterized by fibrosis and a honeycombing of the lungs. There are approximately 40,000 people in the US currently living with IPF. The five year survival rates for patients with IPF is low. New treatment alternatives are needed to improve the survival and lung function for patients suffering from this devastating disease.