VENATORX PHARMACEUTICALS INC — Department of Health and Human Services SBIR Phase I: R

Description

DESCRIPTION provided by applicant Broad spectrum orally bioavailable lactam antibiotics play a critical role in the management of human infectious diseases both in the hospital and community settings facilitating exit from the ICU and treatment in the general ward early discharge and or prevention of hospitalization The rapid spread of lactamase driven resistance in Enterobacteriaceae in both the hospital and community settings is regarded as an emerging healthcare crisis The only orally bioavailable protected lactam amoxicillin clavulanic acid Augmentin discovered over decades ago is ineffective against these new resistance enzymes for example Class A carbapenemases KPC type Class C cephalosporinases Under the auspices of a separate SBIR award we have identified a broad spectrum series of parenteral i v lactamase inhibitors BLIs with activity that extends to Ambler Class A carbapenemases and Class C cephalosporinases Prodrugs of an early prototype in the series demonstrated high oral bioavailability in mice and in vivo efficacy in combination with an oral cephalosporin in a lethal murine septicemia model of bacterial infection This Phase I application endeavors to now marry the Proof of Concept of the earlier prototype work to the more recently optimized parenteral compounds in order to further extend the utility of these BLIs to the oral settings hospital step down and community use Successful realization of this goal would be expected to have a significant medical treatment success and health economic impact avoidance of hospitalization cost and risk of hospital acquired infection PUBLIC HEALTH RELEVANCE Ambler Class A carbapenemases and Class C cephalosporinases are spreading throughout Enterobacteriaceae and pose a serious threat to lactam efficacy in both the hospital and community settings The only orally bioavailable lactam lactamase inhibitor combination on the market Amoxicillin Clavulanate is ineffective against these new resistant strains The combination therapies proposed in this Application including a novel broad spectrum orally bioavailable lactamase inhibitor will directly address this emerging healthcare crisis