Verge Therapeutics — Department of Health and Human Services SBIR Phase II: NIAMS

Description

Acne Vulgaris is a common skin disorder that affectsof the populationtypically teenagers and young adultsOvermillion people in the US are affected by acne generating a $billion market for acne treatmentsof which is derived from prescription medicationsAlthough acne is not a life threatening conditionit still has a high psychosocial impact resulting in depressionanxietyangersuicidal thoughtsphysical scarring and decreased quality of lifeThe primary causes of acne are the overproduction of sebum by sebaceous glandshyperkeratinization of follicular epitheliumPacnes proliferation and inflammationUnfortunatelythe molecular mechanisms of sebum regulation are not clearly understood and this has impeded the generation of safe and effective sebosuppressive therapeuticsRetinoids have been used for more thanyears to treat severe acne and are the only approved therapy that is effective against multiple pathological processes of acneHoweverbecause of serious concerns regarding the teratogenic properties of retinoidstheir use is now part of an FDA mandated registry programIn additionisotretinoin has been linked to serious side effects including clinical depressioninflammatory bowel disease and sensitive skinThere is a clear need for safe and efficacious treatments that target sebum production in sebocytesIn Phase I studies we screened a novel class of compounds identified in a phenotypic screen for peroxisome biogenesis that inhibits sebocyte lipid biosynthesisWe successfully identified active moleculesdeveloped initial structure activity relationship around a lead scaffold and demonstrated in vivo efficacy that is comparable to isotretinoin in an animal model of sebogenesisIn this Phase II application we will use a medicinal chemistry approach to expand this series of compounds using our sebocyte screening platform and in vivo models to identify multiple novel orally bioavailable small molecules for lead optimizationUsing this approachour goal is to deliver safeeffective sebum inhibitors for the treatment of acne vulgaris Acne Vulgaris is a common skin disorder that affectsof the populationincluding overmillion people in the USthe majority of which are teenagers and young adultsA primary cause of acne is excess sebum production by sebocytesUnfortunatelycurrent treatments while effective have severe side effectsincluding birth defectsWe have identified a novel sebosupressive compound class that inhibit sebum production from human primary sebocytes and is equally as efficacious as isotretinoin in animal models of sebogenesis without the serious side effectsThese compounds will be further developed as safe and effective acne therapeutics !