Our Pipeline
APY-GNGPs
We have identified novel orally available arylmyxopyronins–APY-GNGPs–that exhibit potent in vitro activity against Acinetobacter, Burkholderia, and the full set of Gram-positive bacterial pathogens and respiratory atypicals relevant to lower-respiratory-tract infections, including drug-resistant and multi-drug-resistant isolates.
Our current APY-GNGPs exhibit in vitro coverage and potency against Acinetobacter and Burkholderia superior to the current IV drugs Xacduro (surbactam-durlobactam), Unasyn (high-dose ampicillin-surbactam), Fetroja (cefiderocol), and Minocin (minocycline); exhibit in vitro coverage and potency against Staphylococcus, Streptococcus, and Enterococcus superior to the current IV drugs Vancomycin HCl (vancomycin) and Cubicin (daptomycin) and the current IV-oral drug Zyvox (linezolid); and exhibit IV and oral in vivo efficacy in mouse MRSA lung infection and mouse MRSA thigh infection comparable to the current IV-oral drug Zyvox (linezolid).
APY-GNGPs have outstanding IV and oral pharmacokinetics in mice.
APY-GNGPs show no toxicity in mice at doses at least 12 times the dose efficacious in mouse MRSA lung infection.
We are developing APY-GNGPs as novel first-in-class IV-oral treatments for lower-respiratory-tract infections caused by drug-resistant and multi-drug-resistant Acinetobacter, Burkholderia, Staphylococcus, Streptococcus, Enterococcus, and respiratory atypicals.
Competitive Advantages of APY-GNGPs
class novelty
–novel chemical scaffold
–novel binding site and mechanism
–absence of cross-resistance with current antibacterial drugs
–no pre-existing resistance in current clinical isolates
–severe fitness penalties for all resistance mutants
broad coverage
–full coverage of Acinetobacter, Burkholderia, Gram-positives, and respiratory atypicals, including drug-resistant and multi-drug-resistant isolates
–broader coverage of Acinetobacter and Burkholderia than current drugs surbactam-durlobactam, high-dose ampicillin-surbactam, cefiderocol, and minocycline
–broader coverage of Gram-positives and respiratory atypicals than current drugs vancomycin, daptomycin, and linezolid
high oral availability
–IV dosing with oral step-down, enabling inpatient treatment followed by outpatient treatment
–oral dosing, enabling outpatient treatment
high efficacy
–IV and oral efficacy in mouse MRSA lung and thigh infection comparable to the current IV-oral drug linezolid