Value Proposition
- Selective monoclonal antibody therapy to treat lung fibrosis.
- Directly targets immune cells to promote a pro-inflammatory pathway that reduces fibrosis.
- High serum levels are associated with less severe lung disease, decreased fibrosis, and improved survival in a subset of rheumatoid arthritis patients.
- Broadly applicable to other diseases characterized by lung fibrosis.
Unmet Need
Fibrotic lung disease is a disease estimated to affect 50,000 -200,000 people in the USA annually, with many patients developing the disease due to infections or underlying autoimmune disease such as rheumatoid arthritis (RA). Clinically 5-10% of RA patients develop a fibrotic pattern termed usual interstitial pneumonia (UIP) which is incurable, leads to impaired quality of life, and marked shortened survival. The current approved therapy for RA-UIP (i.e. tyrosine-kinase inhibitor, ninetedanib) only modestly slows disease progression and has significant side effects. There is an unmet need for new treatment strategies in RA-UIP and in fibrotic lung diseases more broadly.
Technology Description
Researchers at Johns Hopkins developed an anti-PAD4 monoclonal therapy for the treatment of RA-UIP and fibrotic lung disease. Using a bleomycin mouse model of lung fibrosis, they have found that intrathecal injections of recombinant human PAD4 monoclonal antibodies dramatically reduced accumulation of lung fibrosis in-vivo. Clinical data from RA-UIP patients also show that serum anti-PAD4 antibody levels were associated with less lung fibrosis, better lung function, and decreased mortality. Mechanistic in-vitro studies suggest that PAD4 targets monocytes and promotes a pro-inflammatory phenotype and the secretion of TNF-α which promotes the resolution of lung fibrosis. Together this data demonstrates the therapeutic potential for human anti-PD4 antibodies for the treatment of lung fibrosis.
Stage of Development: Pre-Clinical
Data Availability: Human and mouse data (in-vivo, in-vitro, ex-vivo, clinical)
Publication: Wilson, T.M., Solomon, J.J., Humphries, S.M., Swigris, J.J., Ahmed, F., Wang, H., Darrah, E. and Demoruelle, M.K., 2023. Serum antibodies to peptidylarginine deiminase-4 in rheumatoid arthritis associated-interstitial lung disease are associated with decreased lung fibrosis and improved survival. The American Journal of the Medical Sciences, 365(6), pp.480-487.
