Soligenix, Inc — Department of Health and Human Services SBIR Phase I: NIDCR

Description

Project Summary Abstract This proposal requests funding to support the conduct of the juvenile toxicology study of SGXdusquetidethe first step of embarking on a larger SGXpediatric development programThe major objectives of the study are to confirm the safety of SGXin a juvenile population and to facilitate a safety study in a pediatric patient population at high risk of developing severe oral mucositisSOMMucositis is the clinical term for the painful inflammation and ulceration of the mucous membranes lining the digestive tractusually as an adverse effect of chemotherapy radiotherapy treatment for cancerThe mechanisms of mucositis have been linked to exaggerated response of the innate immune system to the tumor therapy induced tissue damageBacterial infection of the ulcerative lesions is now regarded as a secondary consequence of dysregulated local inflammation triggered by therapy induced cell deathrather than as the primary cause of the lesionsThe pathophysiology of OM is similar in adults and children with the main driver of OM intensity and duration being the chemotherapy and or radiation treatment protocolIn the pediatric populationOM is a frequentsignificant side effect of chemotherapy and radiation treatment used in a variety of underlying diseases including allogeneic hematopoietic stem cell transplantationsolid tumorsand hematologic cancersand for most tumor types there is no efficacious therapy available to treat the primary pathologyOM in pediatrics is often more frequent and more severe than in adults and has substantial impact on the quality of lifeserious infection ratesand impacts the decisions about the duration and intensity of the chemoradiation therapy thatin turncan impact survivalPreclinical studies with SGXrevealed a significant reduction in both duration and peak intensity of oral mucositis caused by either fractionated radiation or chemotherapyIn animal studiesSGXdoes not interfere with recovery from leukopenia and is equally effective in leukopenic animalswhile also providing anti infective activityIDRs have been shown to not interfere with responses of the adaptive immune systemgeneration of antibodiesClinicallySGXhas demonstrated statistically significant reduction of at leastduration of SOM in adult head and neck cancer patients undergoing chemoradiation therapy and is being evaluated in Phasestudy in this same populationThe innate immune system is highly conserved and generally established byyears of agetherefore SGXis expected to be equally efficacious in both adults and childrenTesting in adolescent young adult animals has demonstrated both antiinflammatory and anti infective activityThere is no currently approved therapy for OM in non hematological malignancies and the only approved therapy in hematological malignancies is not considered efficacious in the context of allogeneic stem cell transplantationThe specific aim of the proposal is to confirm the safety of SGXcompared to placebo in juvenile animals with maturing immune systemsincluding evaluation of the adaptive immune systemNKT and B cellsProject Narrative Mucositis is the clinical term for the painful inflammation and ulceration of the mucous membranes lining the digestive tractusually as an adverse effect of chemotherapy and or radiotherapy treatment for cancerthat can be seriously debilitating and that can lead to infectionsepsisthe need for parenteral nutrition and narcotic analgesiaSGXdusquetidehas demonstrated safety and efficacy against oral mucositis in adults with head and neck cancer patientsincidence of severe oral mucositis is andgtjustifying evaluation of treatment of oral mucositis in pediatric patient populations at risk of oral mucositisThis proposal describes the preclinical testing of dusquetidean immunomodulatory peptide that targets the innate immune response that is central to the pathogenesis of oral mucositisin a juvenile toxicology study to confirm the safety of SGXcompared to placebo in juvenile animals with maturing immune systems and this study will facilitate further clinical evaluations in pediatric patients