Kadmon Corporation, which develops first-in-class, innovative therapies against autoimmune and fibrotic diseases, oncology and genetic diseases, recently dosed the first patient in a Phase 2 clinical study of the company’s drug candidate KD025 for the treatment of idiopathic pulmonary fibrosis (IPF).
IPF, a chronic and eventually deadly disease, is characterized by the scarring of lung tissue that causes worsening dyspnea (shortness of breath).
KD025, given orally, is a selective small molecule inhibitor of ROCK2 (rho-associated coiled kinase 2). Preclinical testing indicated that ROCK2 – a key player in multiple autoimmune, fibrotic, and neurodegenerative diseases – can be potentially halted with KD025.
The new clinical trial is an open label, randomized, 24-week study to evaluate the activity, tolerability, and safety of KD025 in patients with IPF in the U.S who have been previously treated with nintedanib and pirfenidone, or either therapy individually.
Thirty-six IPF patients will participate in the study; 24 will be randomly assigned to receive KD025 at 400 mg QD while 12 others will receive standard care.
In the fibrotic tissues of fibrotic diseases such as IPF, there is an up-regulation of the ROCK2, which causes macrophage infiltration, activation of endothelial cells, and differentiation of myofibroblasts. Those biological mechanisms lead to excess deposition of collagen, organ malfunction, formation of scar tissue, and ultimately death.
Results from the pre-clinical studies in a bleomycin-induced mouse IPF model have shown that the inhibition of ROCK2 with KD025 significantly decreased lung fibrosis and inflammation and improved pulmonary function in a dose-dependent manner.
“This study marks Kadmon’s entry into the field of fibrosis, a disease area where we believe ROCK2 inhibition represents a promising new therapeutic approach,” said Dr. Harlan W. Waksal, the company’s president and chief executive officer, in a press release. “Based on our preclinical studies demonstrating the potential anti-fibrotic effects of KD025, we believe our drug may have clinical utility in IPF, a significant unmet medical need.”