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Nasal Leptin - Polymer Conjugate for Treatment of Obesity

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41DK108466-01A1
Agency Tracking Number: R41DK108466
Amount: $215,843.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 300
Solicitation Number: PA15-270
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-08-01
Award End Date (Contract End Date): 2018-01-31
Small Business Information
Raleigh, NC 27612-5419
United States
DUNS: 078296313
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (402) 598-3850
Business Contact
Phone: (919) 923-7401
Research Institution

DESCRIPTION provided by applicant Despite their increased risk of developing serious diseases including coronary heart disease Type diabetes hypertension certain types of cancers and stroke the public health crisis of individuals who are overweight or obese continues unabated Safety issues have hampered development of drugs designed to control weight and the four drugs currently on the market in the U S each has side effects that either limits their use to the very obese or prevents them from gaining wide acceptance in patients Development of new weight loss drugs that are safe and effective with no undesirable side effects remains an important public health goal Leptin is a hormone secreted by white adipocytes and regulates the amount of fat stored in the body by adjusting both the sensation of hunger and by adjusting energy expenditures While Amgen did not succeed in its efforts to gain regulatory approval of recombinant human leptin as a treatment for obesity BMI their studies and those of many others since have yielded a wealth of information regarding the reasons for this outcome Overwhelming evidence suggests that clinical trials with the hormone failed due to the phenomenon of leptin resistance appearing in obese patients especially those with BMIs at the upper end of the scale Computational modeling based on cerebrospinal fluid and serum levels of leptin indicates that in obese individuals BMIandgt leptin levels of about ng ml the inability of the hormone to cross the blood brain barrier BBB accounts for almost two thirds of this resistance It is expected that a form of leptin capable of reaching its receptos in the brain would be an effective therapy for the overweight and mildly obese which accounts for the majority of those at risk for type diabetes Intranasal administration of leptin at the cribriform plate known as intranasal to brain INB delivery enables leptin to enter the brain without exposure to plasma proteases or exclusion by the BBB NeuroNano Pharma Inc is developing a novel formulation of human leptin andquot hu leptiPOL Nandquot in which a single polymer chain of the poloxamer Pluronic r P is covalently attached to the N terminus of the protein In preliminary studies a closely related murine leptin analog with a single P chain randomly attached one of the free amino groups of the protein exhibited lower activity fold as compared to native leptin but displayed a remarkable ability for uptake in brain hypothalamus following INB administration about times higher than that observed with native leptin We propose to optimize the poloxamer modification to produce a more active hu leptiPOL N that following INB administration will exhibit greater receptor activation while retaining the property
of uptake in the brain and brain hypothalamus The overall goal is to provide preclinical evidence that hu leptiPOL N administered intranasally is effective in treating overweight and obesity in the diet induced obese DIO mouse model If the optimized hu leptiPOL N demonstrates superiority to native leptin in brain hypothalamic delivery and in feeding studies in DIO mice we will initiate a development plan to culminate in an IND to commence clinical studies

PUBLIC HEALTH RELEVANCE It is well known that individuals who are overweight have an increased risk for a variety of serious health problems including coronary heart disease Type diabetes hypertension certain types of cancers and stroke NeuroNano Pharma Inc Chapel Hill NC is beginning development of a new drug hu leptiPOL N which is a novel form of the potent appetite suppression hormone leptin and can be administered intranasally to reach the site of action in the brain Based on preliminary data in animals hu leptiPOL N is expected to be safe and effective in treating these patients who are overweight or in the early stages of obesity

* Information listed above is at the time of submission. *

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