AGILE SCIENCES, INC. — Department of Health and Human Services SBIR Phase II: R

Description

DESCRIPTION provided by applicant Antibiotic resistance has been declared one of the three greatest threats to human health by the World Health Organization Infections caused by multi drug resistant MDR bacterial pathogens create substantial health and economic impacts on society due to the lack of effective therapeutic options created by the rapid acquisition of resistance and stagnant antibiotic development programs This lack of treatment options is particularly relevant for MDR Gram negative pathogens such as Pseudomonas aeruginosa Acinetobacter baumanii and Klebsiella pneumoniae which have shown a great propensity to thwart antibiotic treatments and standard hospital disinfection procedures Agile Sciences is developing a novel class of small molecules based on a aminoimidazole AI scaffold that substantially increase the susceptibility of MDR bacteria to antibiotic therapies As an adjuvant therapy to current antibiotics the AI molecules have the potential to provide a much improved treatment option for MDR Gram negative bacterial infections Phase I equivalent work has displayed the potential of AI compounds as antibiotic potentiating agents against MDR Gram negative bacterial pathogens Our efforts have shown that two lead compounds AGL and AGL are able to lower the antibiotic MIC values against MDR Gram negative bacteria an AGL meropenem combination therapy has the ability to enhance survival and decrease bacterial burden compared to meropenem alone in a MDR P aeruginosa acute lung infection model AI compounds possess favorable safety and pharmaceutical profiles and AI compounds act via a novel mechanism of action that retards antimicrobial resistance Collectively this data provides strong support for a continued development program to define the potential therapeutic utility of the AI class of molecules as an antibiotic combination therapy for treating infections caused by MDR Gram negative bacteria In Phase II we will focus development of the AI class of molecules to address the substantial unmet need posed by MDR Gram negative bacterial infections First in Aim we will identify the optimal antibiotic combinations for the lead AI compounds against P aeruginosa K pneumoniae and A baumanii The optimal combinations will be evaluated for pharmacodynamics using the mouse thigh infections mode In Aim the off target effects of AGL and AGL will be evaluated through off target panel screens and characterizations of target binding The AI antibitoic combination with the most promising results in Aim will be evaluated for safety and efficacy in pneumonia and urinary tract infection murine models The efforts in Aim will inform the target product profile TPP of the candidate compound and preliminary scale up work will be performed to facilitate transfer of the synthetic route of the compound to a contract manufacturing organization At the conclusion of this two year grant Agile Sciences will have declared an IND candidate compound and defined the TPP so as to facilitate follow on IND enabling studies PUBLIC HEALTH RELEVANCE The prevalence of multidrug resistant bacterial infections is growing rapidly and these infections are increasingly difficult to treat with existing antibiotics Agile Sciences is developing a new class of small molecules that act via a novel mode of action to enhance the ability of antibiotics to treat infections caused by Gram negative antibiotic resistant bacteria