Drug Discovery for the Treatment of Organ Fibrosis

Organ fibrosis is a serious condition that affects major organs such as the liver, lungs, and kidneys. It impairs organ function, substantially diminishes patients’ quality of life, and is regarded as an intractable disease for which no effective treatment is available. Because fibrosis progresses and recovery of original function becomes difficult once advanced, early treatment is important.

Against this backdrop, drug discovery aimed at treating organ fibrosis has drawn significant attention. The following sections present examples of drug discovery for organ fibrosis and describe the nonclinical studies used in each case.

Case Study: SMC Laboratories, Inc.

SMC Laboratories, Inc. focuses on therapeutic development for fibrotic diseases and conducts drug efficacy evaluations across multiple organs for inflammatory and fibrotic pathologies. In recent work, artificial intelligence identified TRAF2- and NCK-interacting kinase (TNIK) as an antifibrotic target, and a TNIK-targeted therapeutic candidate was evaluated in nonclinical animal models of lung, skin, and kidney fibrosis. The results were reported in Nature Biotechnology.

Nonclinical Studies

Nonclinical studies for this therapeutic candidate used mouse models. In particular, efficacy was evaluated in animal models replicating fibrosis of the lungs, skin, and kidneys. This cross-organ approach enabled evaluation of the same compound across multiple organs and supported advancing development in the most promising indications.

Case Study: Nitto Denko Corporation

Nitto Denko is developing ND-L02-s0201, a therapeutic drug for idiopathic pulmonary fibrosis. This drug is an HSP47 siRNA preparation,Treats fibrosis by inhibiting collagen productionNitto Denko Corporation is developing ND-L02-s0201, a therapeutic candidate for idiopathic pulmonary fibrosis (IPF). This candidate is an HSP47-targeting siRNA therapy designed to treat fibrosis by inhibiting collagen production. In an international Phase II clinical trial, safety and tolerability results were favorable; however, the expected efficacy was not clearly demonstrated.

Nonclinical Studies

Nonclinical evaluation of ND-L02-s0201 used liver fibrosis models. A nonalcoholic steatohepatitis (NASH)–derived liver fibrosis model was also tested; that study was subsequently discontinued.

Summary

Organ fibrosis is designated in Japan as an intractable disease without effective treatment, and multiple approaches are being pursued.

Although antifibrotic drug candidates face many challenges before approval, successful development has the potential to meaningfully improve patients’ lives. Further progress is expected as pharmaceutical companies and bio-ventures utilize drug-evaluation testing services to advance research and development.