SHP-141 is a new molecule in clinical development that is designed to capitalize on the validated mechanism of HDAC inhibition in CTCL, and deliver high drug concentrations locally, directly to skin lesions with negligible toxicity. Because of these features, SHP-141 has potential to be used over large body surface areas without class-associated systemic toxicities of HDAC inhibitors. Specifically, after exerting its activity locally, SHP-141 is designed to break apart into inactive metabolites.
Preclinical studies have demonstrated that topical application of SHP-141 produces substantial HDAC inhibition in the skin, no detectable systemic exposure of SHP-141 or systemic toxicity, even at maximum feasible dose levels.
SHP-141's unique design to minimize systemic impact creates an opportunity for the treatment of other diseases of the skin. Potential for topical HDAC mediation exists for a wide range of inflammatory and proliferative skin conditions, including psoriasis, acne and dermatitis, as well as actinic keratosis and superficial basal cell carcinoma.
The company is currently conducting a randomized, double-blind, placebo controlled, Phase 1b study, to evaluate the safety and tolerability of SHP-141 in patients with Stage 1A, 1B or 2A CTCL [Link to Clinical Trial].
SHP-141 was discovered by James E. Bradner, M.D. of the Dana-Farber Cancer Institute and Ralph Mazitschek, Ph.D. of Massachusetts General Hospital and previously at the Broad Institute of Harvard University and MIT. Shape Pharmaceuticals holds an exclusive patent license covering SHP-141 and other related novel HDAC inhibitors.
Dermal Acetylation in Minipig Skin After Topical Administration of SHP-141