Preclinical in vitro and in vivo studies, presented at the 2016 American College of Rheumatology (ACR) Annual Meeting, demonstrated that in animals models with induced psoriasis, topical application of SM04755 blocked inflammation, keratinocyte (an epidermal cell that produces keratin) proliferation, and fibrosis, and decreased skin thickness in comparison to what is a vehicle (an equivalent to the active drug, but without the active component).
SM04755 is a novel, topical small-molecule Wnt pathway inhibitor that has the potential to treat psoriasis. Wnt signaling plays an important role in psoriasis by regulating inflammation, keratinocyte proliferation, and dermal fibrosis.
The presentation, “Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04755) As a Potential Topical Treatment for Psoriasis,” described preclinical studies that evaluated SM04755 and its potential to prevent inflammation, keratinocyte proliferation (the predominant cell type in the epidermis), and dermal fibrosis, thereby improving skin health in psoriasis.
Results showed that in a mouse model of psoriasis, topically applied SM04755 demonstrated potent and selective inhibition of Wnt signaling, inhibiting inflammation, and decreased skin thickness compared to vehicle, with minimal plasma exposure or systemic toxicity.
“Based on our study results, we are excited about SM04755’s potential as a treatment for psoriasis. Treatment of mild to moderate psoriasis using a safe and effective topical agent remains an area of intense medical research,” Yusuf Yazici, chief medical officer of Samumed, said in a press release. “Our Phase 1 trial for chronic tendinopathy using the same topical investigational drug will form the basis to expand into a Phase 2 study for psoriasis in 2017.”
SM04755 is one of two Wnt pathway modulators for which Samumed presented clinical and/or preclinical data across five different rheumatic diseases at the ACR meeting. The other Wnt pathway modulator, SM04690 is currently in clinical trials for osteoarthritis and degenerative disc disease.
Psoriasis is an auto-immune disease of the skin, characterized by inflammation and fibrosis, producing patches of red, itchy and scaly skin. It affects about 2 percent of people worldwide.
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