RADIKAL THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase II: NIAMS

Description

Radikal TherapeuticsRTXis developing a pioneering therapy to restore immunotolerance and arrest progressive depigmentation in vitiligoAt our partnering institutionLoyola University Chicagoa variant to inducible Heat Shock Proteinwas developed with remarkable potential for the prevention and treatment of autoimmune vitiligoCarrying only a single amino acid modification to the proteinthis variant HSPiQACMwas found to have a curative effect involving long lasting tolerization of dendritic cellsDCsand inhibition of T cell influx to the skinIn the PhaseSBIR we examined the CM in a model of spontaneous depigmentation in Sinclair swinecharacterized by regressing melanoma and newly developing vitiligoParalleling the clinical presentationin this system the inflammatory CDb CDcsubset of DCs held responsible for precipitating and perpetuating vitiligo is found in increased abundance among circulating and skin infiltrating DCWe observed that untreated lesions in the control group gradually increased in size bywhereas repigmentation ofwas observed in CM treated lesionspThis change in cutaneous pigmentation was associated in treated pigs with areduction in infiltrating T cellspandltWe thus hypothesize that the CM encoding DNA will likewise interfere with progressive depigmentation in human vitiligo patientsproviding incentive for the development of the CM into a marketable drugAimScale up and produce GMP grade CM The PI will synthesize de novo a high producing Ecoli clone expressing the CM plasmidRTX will finalize optimization of the growth conditionsdevelop product specific HPLC release assaysand generate a reference standardAldevron will generate a Master Cell Bank and Working Cell Bank expressing the CMand generate a g GMP batch of the CM in order to support clinical Phasea safety and efficacy investigations in clinical vitiligoand to perform stability analysisAnalytical methods will be developed to characterize the CM for GMP release and stability studiesAimRelate CM treatment efficacy to disease duration in a murine model of vitiligoRTX will measure efficacy of the CM in relation to disease duration in h TAmice with progressive vitiligoWe will treat miceweeks at age at onset to measure disease arrest and repigmentiation by scanningAimEstablish the acute safetytoxicityand tolerance of CM in GLP toxicology studies required for FDA IND applicationRTX will carry out aweek GLP study wherein the CM is dosed via a subcutaneous route of administration in order to elucidate the NOAEL in mice and provide the basis for the dose range to test for safety and tolerance in manAimCompile and prepare a pre IND application to the FDA RTX will prepare and submit regulatory documentation to support a clinical GCP Phasea study to evaluate the safety of the CM in human volunteers with active vitiligoRTX will meet with the FDA to present our efficacy data to gain concurrence on a clinical registration pathway leading to drug registration inWe are proposing a novel pharmaceutical therapy to block the progression of vitiligoa disease in which skin pigment is lostresulting in progressive growth of lesions with out skin colorOur drug is a novel entity that targets the basic mechanisms of vitiligo and is intended as a lifelong therapyWe will undertake requisite manufacturing to prepare a supply of drug for preclinical and safety examinationcarry out FDAmandated toxicology studies in miceand prepare to perform the first trial of the drug in humans with active vitiligo