Regranion, LLC — Department of Health and Human Services SBIR Phase II: NIAMS

Description

PROJECT SUMMARY Psoriasis is a chronic inflammatory skin disease affecting approximatelymillion Americans that can become debilitating and severely impact quality of lifeWhile an estimatedof patients suffer moderate to severe disease forms that require systemic therapy with immune suppressants and ultraviolet phototherapythe majorityof patients exhibit milder symptomsFor these patientstopical agents such as steroidsvitamin D analoguesand calcineurin inhibitors are prescribed but remain associated with poor efficacy and tolerabilityDespite advances in the development of targeted biologicsincluding cytokine inhibitorsmany psoriasis patients remain inadequately treated due to the risk of serious adverse side effectsloss of efficacy and high costThere is a pressing need for the clinical development of effectivesafeeasy to useaffordable topical psoriasis therapeutics that target the upstream proteomic mediators of the diseaseHuman psoriatic lesions have a profound upregulation of HSPversus normal skinwhere data support a role in the interplay between the innate and the adaptive immune systemRegranion has recently acquired a potent novel small molecule HSPinhibitor with a good safety profile and proven preclinical and anecdotal clinical efficacy data for the treatment of psoriasisIn a xenograft transplantation model of psoriasisoral delivery of CTXTpreviously called Debioresulted in significant clinical alleviation of psoriasisreduced epidermal thicknessand dramatic reduction in levels of TNFand ILpro inflammatory cytokines linked to the persistence of psoriasisSimilarlytopical delivery of CTXTsignificantly decreased psoriatic symptoms in psoriasis mouse modelsClinical safety of CTXThas been validated in a CTXTPhaseoncology trialwhere afterdays of daily treatment withmg CTXTa patient with severe psoriasis covering more thanof the skin surface showed complete remissionBased on this supporting preclinical data and serendipitous clinical findingwe plan to develop CTXTin a topical formulation targeting patients with mild to moderate forms of plaque psoriasisOur strategy is to address the wider and pressing unmet need for patients with mild to moderate from of psoriasis with topical delivery of CTXTto be followed by an oral form in the future for severe psoriasisThe major objectives of this SBIR Phase II proposal are threefoldA rigorous evaluation of the efficacy and mechanism of action of topical CTXTwill be performed in a clinically validated psoriasis model that incorporates a comparative efficacy study versus topical corticosteroid treatmentcompletion of necessary IND enabling GLP dermal sensitivitydermatopharmacokineticand toxicokinetic studiesandpreparation and submission of an IND package for a future Phasebhuman clinical studyFurthermorethe proposal will enable the formulation of a clinical and regulatory strategy for accelerated developmentThe completion of the Phase II SBIR aims will provide full characterization of CTXTin a topical formulation in order to advance into clinical trials following IND approval