SBIR/STTR Award attributes
PROJECT SUMMARYHPV is the United Statesmost prevalent sexually transmitted infection and the high risk subtypes are ofsignificant public health interest given that high risk HPVHR HPVinfections have been conclusively linkedto the development of certain cancersCervical intraepithelial neoplasiasCINcaused by persistent HR HPVinfectionare categorized by gradewith high gradesandbeing considered precancerous and gradecarcinoma in situWhile there are an estimatedtomillion women diagnosed with CIN annually in theU Sthere are no minimally invasive therapies with direct antiviral activity for the treatment of CIN andexcisional procedures are often associated with painfertility issues and recurrenceDespite the success of theprophylactic HPV vaccinesthe incidence of HPV induced cancer is steadily increasingdue toathe inabilityof the vaccine to cure preexisting infectionsba great majority of adolescent populations is not vaccinatedandchigh rate of population growthNovan s platform technology enables the delivery of nitric oxide in a solid formon demand and in localizedformulationsNovan s nitric oxideNOreleasing drug candidates have demonstrated the ability to inhibitpapillomavirus amplification and replication in nonclinical modelsas well safety and efficacy in a Phasetrialof external genital wartsThe goal of this Fast Track research plan is to develop a new formulation of a nitricoxide releasing gel that can be self administered by the patientintravaginallyas a treatment for cervical HPVinfections in womenIf successfulsuch an approach may be instrumental in reducing the number of locallydestructive surgical procedures in the U Sandultimatelycervical cancers attributable to HPVThe Phase I portion of this research proposal is designed to formulate a stable gel formulation suitable forintravaginal administration and ensure the NO release profiles of the gel replicate profiles previouslydemonstrated to have antiviral effectsGo no go criteria to transition from Phase I to Phase II is minimumstability of the formulation intended for clinical use in the U SC forweeksand an NO release profilethat matches the high C max and short half life release profile previously demonstrated to have antiviral activitywhen delivered topicallyThe Phase II portion is designed to assess the gel formulation sin vitro toxicologytumor promotion capabilities and effect on vaginal florain vivo toxicologysafetytolerability andtoxicokinetics following application to mucosal surfaces via intravaginal administration in aday pilot and aGLPday repeat dose toxicology study in rabbits necessary to submit an Investigational New DrugINDapplicationpharmacologyability to reduce vaginal papillomavirus infections and regress cervicalneoplasias in a mouse modelandvirologyevaluation of NO s antiviral activity and mechanism of actionagainst HPVinfected cellsThe body of this work constitutes the foundational nonclinical studies necessaryto submit an Investigational New DrugINDapplication to the FDA PROJECT NARRATIVE Persistent high risk human papillomavirusHR HPVinfection is the most important risk factor for the development of cervical intraepithelial neoplasiasCINin women and the subsequent progression to cervical cancerWhile there are an estimatedtomillion women diagnosed with CIN annually in the U Sthere are no minimally invasive therapies with direct antiviral activity for the treatment of CINExcisional treatment procedures are associated with increased risk of pre term birth in future pregnancies as well as anxietypain and bleedingNovan is developing a nitric oxide releasing antiviral gel for the treatment cervical HPV infections and the prevention of downstream malignancies in women
