MONON BIOVENTURES LLC — Department of Health and Human Services SBIR Phase I: 200

Description

PROJECT SUMMARY Hypoglycemiaa decrease in blood sugar levelsis a common occurrence for themillion Americans with diabetesIn severe hypoglycemiathe individual is at risk for diabetic coma and even deathAlthough these events can be managed using a glucagon emergency kitcurrent kits require a multi step procedure in which lyophilized glucagon is reconstituted and administered as an injectionEmergency kits are associated with a high rate of user error and frequently go unusedAdditionallykits are often not available when neededas diabetic individuals find them cumbersome and rely on emergency room visits to treat severe hypoglycemiaThe misuse and underutilization of glucagon emergency kits can be traced to the limited solubility and stability of glucagonGlucagon is supplied as a powder in the kits because it is unstable in solutionrapidly forming amyloid fibrilsAdditionallyglucagon has limited solubility at neutral pH and is solubilized in acidic pH in the kitsMonon Bioventures is developing glucagon derivatives with enhanced stability and solubility to provide a more versatile and user friendly productMonon Bioventuresapproach involves using reversible phosphorylation of glucagon to prevent the formation of amyloid fibrilsthus creating a solution stable glucagon derivativeknown as phospho glucagonPreliminary efforts have identified phospho glucagons with improved solubility and stability and have shown increases in blood glucose comparable to native glucagonin ratsThese data support the continued development of lead phospho glucagons through a Fast Track program that is geared toward generating target product profilesTPPsfor intranasal and self injectable intramuscular phosphoglucagon formulationsThis overall goal will be met through the execution of the following aimsPhase I Specific Aims areTo execute formulation studies and structural modifications of lead phospho glucagons to improve oxidative stabilityTo develop and validate analytical methods for phospho glucagon in plasmaThe measures of success to advance to Phase II areidentification of at least two candidate phospho glucagons formulated in solution at a neutral pH that have desired stabilityandltoxidation atoC formonthsno detectable fibrillationsolubilityandgtmg mLand functionalityincreases blood glucose at rate and extent similar to native glucagonanda validated bioanalytical method with a limit of detection ofng mL or lessPhase II Specific Aims areTo determine long term stability of lead phospho glucagon formulationsTo assess the PK pharmacodynamicPDproperties of phospho glucagon formulationsTo generate preliminary safety and immunogenicity profiles of the lead phospho glucagon formulationsThe measure of success for Phase II is to complete key pharmacological and safety assessments to construct the TPP PROJECT NARRATIVE Severe hypoglycemiawhich involves a large drop in blood sugar that can result in diabetic coma and even deathis a significant risk for themillion Americans living with diabetesThese episodes can be successfully treated with timely and proper administration of glucagon by a third party using an emergency kithoweverthis treatment is often underutilized or inadequately used due to a complex administration protocol that results from solubility and stability limitations of glucagonMonon Bioventures seeks to develop a solution stable phosphoglucagon prodrugthat would enable intramuscular and intranasal delivery of a rescue dose of glucagonNovel solutions of phospho glucagon will allow for emergency glucagon delivery regimens significantly more user friendly than kits that are either currently marketed or under development by competitorsAvailability of such kits will increase utilization and proper administration of this life saving intervention for severe hypoglycemia