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Retinoids, which include Vitamin A (retinol) and its analogues (both synthetic and metabolites), play a critical role in cell signaling and biological processes, including regulation of immune cells and inflammation, signaling pathways that control normal skin maintenance, embryonic development, and cell growth/differentiation/repair. Deficiencies in retinoids and their active metabolites have been implicated in a wide variety of diseases. In the skin, retinol deficiency leads to hyperkeratosis and keratinizing metaplasia that is observed in skin disorders like psoriasis and acne. Vitamin A and retinoic acid also play a crucial role in regulating cell proliferation, differentiation, and apoptosis and therefore, altered metabolism of retinoids has been suspected as a potential role in tumorigenesis. Accordingly, retinoids have been approved in the US for treatment of acne and psoriasis as well as other therapeutic indications (such as acute promyelocytic leukemia and cutaneous T-cell lymphoma); however, the therapeutic use of exogenous retinoids has been limited due to negative effects associated with high systemic concentrations.
A new therapeutic approach to increase intracellular retinoic acid (the active metabolite of retinol) potentially without causing negative side effects of exogenous retinoic acid is to use inhibitors of retinoic acid metabolism (collectively called RAMBAs), which prolong the presence of retinoic acid. HT-003 is a novel RAMBA under investigation for topical treatment in acne and psoriasis applications.
HT-003 is currently in the early preclinical stages of development.
In December 2019, Hoth Therapeutics entered into a research collaboration agreement with Weill Cornell Medicine for completion of preclinical studies investigating the mechanism of action of HT-003.
Dr. Jonathan Zippin, M.D., Ph.D., FAAD, Associate Professor of Dermatology at Weill Cornell Medicine and HOTH Senior Scientific Advisor, will be the Principal Investigator for the research collaboration. Initial results released September 24, 2020
Next phase of preclinical studies initiated Q1 2021