Our Pipeline​

APY-GNGPs

We have identified novel orally available arylmyxopyronins–APYs-GNGPs–that exhibit potent antibacterial activity against drug-susceptible, drug-resistant, and multi-drug-resistant isolates of the Gram-positive bacterial pathogens Staphylococcus, Enterococcus, and Streptococcus; the Gram-negative bacterial pathogens Acinetobacter and Burkholderia; and the respiratory atypical bacterial pathogens Haemophilus, Moraxella, Legionella, Chlamydia, and Mycoplasma.

APY-GNGPs exhibit in vitro coverage of drug-resistant and multi-drug-resistant Staphylococcus, Enterococcus, Streptococcus, Acinetobacter, and Burkholderia substantially superior to current standards of care and current second- and third-line drugs.
 
APY-GNGPs exhibit in vivo efficacy in intravenous treatment of mouse methicillin-resistant Staphylococcus aureus (MRSA) lung infection and MRSA thigh infection comparable to or superior to the IV-only standard of care vancomycin, and exhibit in vivo efficacy in intravenous and oral treatment of mouse MRSA lung infection and MRSA thigh infection comparable to the intravenous/oral standard of care linezolid. APY-GNGPs also exhibit in vivo efficacy in treatment of mouse carbapenem-resistant Acinetobacter baumannii (CRAB) lung infection
 
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, intravenous/oral treatments for lower-respiratory-tract infections caused by drug-resistant and multi-drug-resistant Staphylococcus, Enterococcus, Streptococcus; Acinetobacter, Burkholderia, 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 Gram-positives and respiratory atypicals relevant to lower-respiratory-tract infections, including drug-resistant and multi-drug-resistant isolates
–0% non-susceptibility in current clinical isolates of Staphylococcus (major advantage over standards of care vancomycin, daptomycin, and linezolid)
–0% non-susceptibility in current clinical isolates of Enterococcus (major advantage over standards of care vancomycin, daptomycin, and linezolid)
–0% non-susceptibility in current clinical isolates of Streptococcus (major advantage over standard of care daptomycin)

high lung penetration and low lung surfactant binding
–effective against lower-respiratory-tract infections (major advantage over standard of care daptomycin)

high oral availability
–IV and oral dosing (major advantage over standards of care vancomycin and daptomycin)

high efficacy
–IV efficacy in mouse MRSA lung and thigh infection comparable to or superior to IV-only standard of care vancomycin
–IV efficacy in mouse MRSA lung and thigh infection comparable to IV/oral standard of care linezolid
–oral efficacy in mouse MRSA lung and thigh infection comparable to IV/oral standard of care linezolid