API SM04554

SM04554 More Info

SM04554, also known as Dalosirvat, is a small-molecule Wnt pathway modulator and a topical Wnt pathway activator. It is being investigated as a potential topical treatment for androgenetic alopecia (AGA), which is characterized by progressive hair follicle miniaturization and decreased hair growth. The Wnt signaling pathway plays a critical role in the self-renewal and fate determination of mesenchymal stem cells and is involved in the development of multiple tissues, including hair follicles. In AGA, Wnt pathway activity is decreased, which reduces follicle proliferation and hair growth. SM04554 is hypothesized to promote hair growth by disinhibiting the Wnt signaling pathway.

In preclinical studies, topical SM04554 demonstrated safety and efficacy. It led to biologically active compound levels in the skin with minimal systemic exposure and appeared to be safe and well tolerated compared to the vehicle. Genotoxicity studies showed no mutagenic signal, and no dermal safety signals were observed up to the highest formulable dose in dermal toxicity studies. SM04554 increased Wnt signaling and hair growth in mice, shortening the telogen phase and accelerating the anagen phase.

In Phase 1 studies, SM04554 appeared safe and well tolerated when dosed daily for 14 days, with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. Most adverse events were considered unrelated to the study medication by the investigator, and laboratory parameters, ECGs, and vital signs were unremarkable during the study. Systemic exposure was low, with low concentrations in plasma (≤1.21 ng/mL), but not detected in all subjects at all time points.

In the Phase 2 study (SM04554-AGA-02), which was a multicenter, randomized, double-blind, vehicle-controlled study, 302 subjects aged 18-55 with diagnosed AGA were enrolled. The study evaluated the safety and efficacy of 0.15% and 0.25% SM04554 compared to a vehicle over a period of 135 days. The primary outcomes included safety and tolerability, while secondary outcomes included hair growth by investigator scale, quality of life by Kingsley Alopecia Profile (KAP), hair density by macrophotography, and quantification by macrophotography of non-vellus hair count. The results showed that SM04554 appeared safe and well tolerated, with adverse event frequency similar across all treatment groups and placebo. The most common related adverse events were application site erythema, pruritus, and paresthesia. SM04554 increased non-vellus hair counts from baseline, with 0.15% SM04554 significantly improving hair count at Day 135 compared to the vehicle.

In summary, SM04554 is a promising investigational compound for the treatment of androgenetic alopecia, with positive hair bioactivity documented at both macro and micro levels in clinical studies. However, it is important to note that SM04554 has not been approved by the U.S. Food and Drug Administration (FDA) or any other pharmaceutical regulatory authority, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidate.