2021-08-31
Dosing completed in the first cohort of the first-in-human (FIH) study for SHR-1906, an anti-CTGF antibody with optimized molecular design and prolonged half-life
Hengrui Pharma lately announced that dosing has been completed in the first cohort (12 healthy subjects) of the ongoing SHR-1906 Phase I FIH study.
About the study
The Phase I FIH trial (NCT04986540) is a randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of SHR-1906 in approximately 48 healthy subjects (4 dose escalation cohorts, 12 subjects in each).
About SHR-1906
SHR-1906, a potential best-in-class humanized monoclonal antibody targeting connective tissue growth factor (CTGF), is being developed by Hengrui with optimized molecular design and prolonged half-life to treat idiopathic pulmonary fibrosis (IPF). In vitro studies demonstrated that SHR-1906 could efficiently inhibit the activity of CTGF by blocking the binding between CTGF and TGFβ. In addition, preclinical data showed that SHR-1906 could reduce scar tissue formation and preserve organ structure and function in bleomycin-induced IPF model.
About idiopathic pulmonary fibrosis (IPF)
IPF is a rare, progressive illness of the respiratory system. With a median survival of 3–5 years following diagnosis, IPF is characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue.1 The adjusted incidence and prevalence of IPF are estimated to be in the range of 0.9–13.0 and 3.3–45.1 per 100,000 persons, respectively.2
About connective tissue growth factor (CTGF)
Connective tissue growth factor (CTGF) is a member of a small family of proteins that are characterized by their highly conserved disulfide bonding pattern and having 3-4 domains with homology to other proteins. CTGF is a secreted matricellular protein with complex biology. It modulates multiple signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis.3 Previous studies also showed that CTGF might be of paramount importance for the development of the characteristic desmoplastic reaction in pancreatic cancer tissues.4
1. Estrella FF, et al. Prognosis and Follow-Up of Idiopathic Pulmonary Fibrosis. Med. Sci. 2018; 6, 51.
2. Toby MM, et al. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respiratory Research. 2021; 22:197.
3. Lipson KE, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis[J]. Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S24.
4. Takeshi T, et al. Dysregulation of PI3K and Hippo signaling pathways synergistically induces chronic pancreatitis via CTGF upregulation. J Clin Invest. 2021 Jul 1;131(13):e143414.