AJ303 is a novel first-in-class compound with anti-fibrotic and anti-inflammatory properties currently under development for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases. Using human primary cell-based models of pulmonary and renal fibrotic diseases, AJ303 was shown to decrease the levels of pro-inflammatory cytokines, epithelial-mesenchymal transition markers, as well as extracellular matrix (ECM) proteins, in which their aberrant expressions are thought to drive the fibrosis. In bleomycin-induced rodent models of IPF, AJ303 was shown to reduce the levels of TGF-β and IL-6 in the bronchoalveolar lavage fluid and the fibrotic lesions (scars) in lung. In addition, AJ303 has a favorable ratio of plasma to lung tissue distribution in non-clinical pharmacokinetic studies.

Idiopathic Pulmonary Fibrosis (IPF)

IPF is a chronic progressive fibrotic interstitial lung disease of unknown etiology leading to the irreversible damage and decline in lung functions. The pathological hallmark is characterized by excessive deposition of ECM resulting in tissue scar formations in the lungs. At the molecular and cellular levels, it is believed that the dynamic biological process of IPF reflects the abnormal tissue repair mediated by complex interactions between epithelial cell injury, immune cell activation and fibroblast proliferation. Some key signaling pathways, such as those mediated by TGF-β and PDGF, are thought to be dysregulated in IPF with the functional consequence of altering the normal ability of the lung to respond to injury. Despite being considered a rare disease, IPF affects approximately 3 million people worldwide. The overall disease prognosis of IPF remains poor with a median survival time of 2-5 years from the initial diagnosis.

Anti-fibrotic and anti-inflammatory effects of AJ303 in fibrosis

Clinical Development

1. IND in preparation for submission in 1H2022
2. First-in-human clinical trial is anticipated in 2H2022

References

1. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020 Aug;8(8):807-815
2. Idiopathic pulmonary fibrosis: lessons from clinical trials over the past 25 years. European Respiratory Journal 2017 50: 1701209
3. Idiopathic pulmonary fibrosis. Nat Rev Dis Primers. 2017 Oct 20; 3:17074
4. Real World Experiences: Pirfenidone and Nintedanib are Effective and Well Tolerated Treatments for Idiopathic Pulmonary Fibrosis. J Clin Med. 2016 Sep 2;5(9):78