PERIPHERALLY-RESTRICTED LONG-ACTING SOMATOSTATIN RECEPTOR TYPE 4 (LA-SSTR4) AGONISTS FOR PAIN

PROJECT SUMMARY The proposed program seeks to develop a first in classFICperipherally restricted and long acting somatostatin receptor typeLA SSTRagonist as a peripheral analgesic for the treatment of moderate tosevere acute and chronic painThe program is based on strong scientific evidence showing that activation of peripheral SSTRproduces broad spectrum analgesic activityWe propose to conjugate existing peptidic SSTRagonist pharmacophores to a clinically validated antibody carrierpreviously used successfully to create peripherally restricted long acting kappa opioid receptorLA KORagonistsThe resulting peptide antibody conjugate will retain activity at SSTRwhile acquiring the pharmacokineticPKproperties of the antibody carrierthereby achieving bothilong elimination half life andiihigh peripheral selectivityThese two key features will provide peripherally restricted LA SSTRagonists with a markedly differentiated and superior target product profileTPPin terms of efficacysafety and convenience compared to short acting and brain penetrating small molecule SSTRagonists pursued by competitorsThe extended half life will enable less frequentsimpler and more convenient administrationi eonce weeklyQWor twice monthly subcutaneousSCdosingthat in turn will improve complianceensure continuous drug exposureand ultimately maximize efficacyThe lack of penetration in the central nervous systemCNSis critical as it will prevent unnecessary and undesired interaction with abundantly expressed SSTRin the CNSthereby eliminating any risk of CNS mediated SSTRside effectsFurthermoreunlike opioidsSSTRagonists do not induce constipationrespiratory depressiondependenceaddiction or abuseFinallySSTRexpression in the pituitary and pancreas is very lowunlike SSTRand SSTRsuggesting that selective SSTRagonists are unlikely to perturb peripheral endocrine functionsThis SBIR Phase I proposal is designed to assess the feasibility of creating potentselective and stable LA SSTRagonistsThe follow up Phase II program will include further lead optimizationevaluation of efficacypotency and duration of action in acute and chronic pain modelsPK studies and selection of a clinical candidate new molecular entityNMEfor preclinical developmentIMPACT andampPROJECT NARRATIVE This program seeks to develop a novelsafe and convenient analgesic that will benefit both patients and society by improving quality of life through effectivenon addictive and better tolerated pain control while providing therapeutic alternatives that can help in curbing theprescription opioid epidemicand reducing opioid substance use disorderSUD