Orally bioavailable small molecule for the treatment of Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a fatal, chronic progressive lung disease associated with the formation of scarring tissue and worsening respiratory lung function. IPF is the most common type of fibrotic lung disease. Unfortunately, the exact cause of the disease is not known yet, but it is assumed that scarring matters, such as air pollution, dust, smoking, and genetic factors, might induce lung fibrotic disease. Uncontrolled myofibroblasts exist longer time and continuously accumulate in the extracellular matrix, which makes alveolar tissue rigid and lose its functional activity. Patients diagnosed with IPF have a poor prognosis, meaning life expectancy is between 3 to 5 years, with less than 30% of patients surviving beyond 5 years.
So far, two drugs, pirfenidone, and nintedanib have been approved for the treatment of IPF since 2014. However, the two medicines just slow the decreasing rate of respiratory capacity and are not able to extend the life expectancy of the patients. In addition, because of the various adverse effects that accompany the two drugs, it is hard to take them for more than 2 years. So, IPF therapeutic market still has a large unmet medical need and a huge number of trials to develop novel drugs are actively performed by big pharmaceutical companies as well as bio ventures. For a long time, the strategy of drug development for IPF has been focused on kinase-related mechanisms, many pipelines were based on kinase inhibitors. Recently, the development of ziritaxestat, an autotaxin inhibitor was discontinued at the stage of phase 3 clinical trial. Many pipelines are under development by focusing on a variety of targets, such as CTGF-binding factor, pentraxin-2, phosphodiesterase 4B, calpain, lysophosphatidic acid receptor-1, c-Jun N-terminal kinase, Rho-associated protein kinase 2, autotaxin, etc.
SapiensBio set novel target mining as the strategy to develop therapeutic drug to address a huge unmet medical need on IPF. To identify novel therapeutic target, SapiensBio collected single cell RNA sequencing (scRNA-seq) data from the lung tissues from IPF patients as well as normal humans and analyzed the data with a cell-type transition tracking manner using Sapientia. TARGET-X, which has never been studied in fibrotic disease, was identified and validated as a novel target by in-house wet lab facilitation of the Sapientia platform. AI-1097, a novel compound that directly binds and controls the TARGET-X, is generated using the ligand-based drug development (LBDD) module and fibrosis-specific chemical library of Sapientia. AI-1097 shows a very nice therapeutic efficacy in bleomycin-induced lung fibrosis model studies and a high safety in both in vitro and in vivo safety tests. The promising novel compound is at the latest stage of lead optimization to a clinical candidate for IPF treatment.
Fibrotic diseases can occur in various organs including the liver, kidney, heart pancreas, skin as well as lungs. Because SBC101 showed an excellent therapeutic efficacy on lung fibrosis, it is expected that SBC101 will be relevant to apply to other fibrotic diseases. So, SapiensBio is trying to expand the range of indications that can be treated by SBC101. Recently, SBC101 was confirmed that has a promising therapeutic effect on hepatic fibrosis using a human hepatic stellate cell model and a series of in vivo efficacy studies are under preparation.