Lyndra Therapeutics, Inc. — Department of Health and Human Services SBIR Phase II: NCATS

Description

PROJECT SUMMARYAn Oral Ultra Long Acting Ivermectin for Malaria Elimination Despite effective treatmentsmalaria remains a scourge of sub Saharan AfricaAdditional interventions beyond those currently available are needed to eliminate the diseaseOne strategy with increasing support is addition of ivermectina well known and safe drug used for treating onchocerciasis and other diseasesto current mass drug administrationMDAcampaigns with artemisinin regimensIvermectin has a unique activity in interrupting malaria transmission in endemic areas by reducing the life expectancy of the vector anopheles mosquitos that bite subjects who have ivermectin in their bloodModelingas well as proof of concept field studieshave shown that longplus daycourses of small doses of ivermectinin combination with short courses of currently used artemisinin combination MDAhave the potential to reduce the efficiency of malaria transmissionreduce malaria casesand potentially lead to disease eliminationTreating evenof the population in this way can reduce disease transmission to levels that can protect the whole populationincluding children undermost at riskTo be effectiverepeat dosing every three days would currently be necessarylimiting feasibilityDevelopment of an ultra long acting oral ivermectin formulation that achieves single dose administration and prolonged low level blood exposure could dramatically change current treatment optionsreduce malaria morbidity and potentiate malaria elimination effortsNo existing oral delivery system can prolong therapeutic blood levels for small molecules therapeutics beyondhoursWe have developed prototype oral capsules based on Lyndra s gastric residence technology that can achievedays of sustained therapeutic ivermectin levels in a pig model and have shown similar efficacy with other drugs in multiple large animal modelsThe goal of this grant is to develop an optimal ivermectin dosage form thatachieves consistent and efficacious blood levels of ivermectin fordays from a single dose administrationdevelop a reproducible and scalable low cost manufacturing capabilityandevaluate these dosage forms with respect to pharmacokinetics and gastric retention in beagle dogsFormulations will be developed to pharmaceutical grade standards of in vitro release and stability under Tropical Zoneb standardsMethods of production compatible with low cost of goods production and scale will be prototypedDosage forms will be evaluated in extensive preclinical pharmacology studies in beaglesincluding stress conditionsand a toxicology study will be performedThis grant will deliver a product ready for IND enabling studies and create capability for GMP production of clinical specimens for a phasehuman pharmacokineticPKstudy of ultra long acting Lyndra IvermectinThis Direct to Phase II grant builds on three years of work and ample preliminary data