Peripherally-Restricted Long-Acting Somatostatin Receptor 4 (LA-SSTR4) Agonists for Pain

PROJECT SUMMARY ABSTRACT The proposed SBIR Phase II program seeks to select a first in classperipherally restrictedand long acting somatostatin receptorLA SSTRagonist clinical candidate for development as a novel non addictive analgesic able to replace opioids for the treatment of moderate to severe chronic painThe program is based on strong scientific evidence showing that activation of peripheral SSTRproduces broad spectrum analgesic activity and pursues a unique therapeutic strategyLA SSTRagonists are semi synthetic biologics created using a proprietary peptide antibody conjugatePACtechnology and having the following modular structurepeptidespacerlinkerantibody carrierThe peptide module confers agonist activity at peripheral SSTRwhereas the antibody carrier provides extended duration of action and peripheral selectivityThese unique features will allow us to achieve a markedly differentiated and superior product profile in terms of efficacysafetyand convenience compared to short acting and brain penetrating small molecule SSTRagonistsThe extended half life will enable once weekly to once monthly subcutaneous dosingthereby maximizing conveniencecomplianceand efficacyThe lack of penetration in the central nervous systemCNSwill prevent unnecessary and undesired interaction with abundantly expressed SSTRin the CNSeliminating any risk of CNS mediated SSTRadverse effectsthereby maximizing safetyUnlike opioidsSSTRagonists do not induce constipationrespiratory depressiondependenceaddictionor abuseFinallyunlike SSTRand SSTRSSTRexpression in the pituitary and pancreas is very lowsupporting that selective SSTRagonists are unlikely to perturb peripheral endocrine functionsThe preceding SBIR Phase I program has already established the feasibility of conjugating a short actingpotentand selective peptide SSTRagonist to the antibody carrierThe resulting LA SSTRagonist lead series has high agonist potency and selectivity for SSTRand has demonstrated antinociceptive activity in an animal pain modelThe proposed SBIR Phase II program seeks toAimoptimize the existing lead series and select a clinical candidate for developmentAimvalidate and prioritize the indication sfor clinical development using disease relevant mouse pain modelsand Aimcharacterize the pharmacokinetics and safety toxicology profile of the clinical candidate in rat and non human primates to help design subsequent investigational new drugINDenabling studiesAssuming success with the current proposalthe follow up Phase IIb program will establish good manufacturing practicesGMPproduction for the clinical candidate and complete the good laboratory practicesGLPsafety toxicology studies required for the IND applicationIMPACT andampPROJECT NARRATIVE This program seeks to develop a novelsafeand convenient analgesic that will benefit both patients and society by improving quality of life through effectivenon addictiveand better tolerated pain control while providing therapeutic alternatives that can help curb theprescription opioid epidemicand reduce opioid substance use disorderSUD