Our Pipeline
APY409/461
We have identified novel orally available arylmyxopyronins–APYs–that exhibit potent in vitro activity against the full set of Gram-positive bacterial pathogens and fastidious Gram-negative bacterial pathogens–including drug-resistant, multi-drug-resistant, and pan-resistant isolates–relevant to lower-respiratory-tract and skin-and-soft-tissue infections.
Our current APY lead, APY409/461, exhibits in vitro coverage and potency superior to the current standard-of-care oral drug Zyvox (linezolid) and exhibits oral in vivo efficacy in mouse MRSA lung infection and mouse MRSA thigh infection comparable to the current standard-of-care oral drug Zyvox (linezolid).
APY409/461 has excellent oral pharmacokinetics in mice.
APY409/461 shows no toxicity in mice at doses at least 12 times the dose efficacious in mouse MRSA lung infection.
We are developing compounds of the APY409/461 subclass as novel first-in-class oral treatments for lower-respiratory-tract infections and skin-and-soft-tissue infections by drug-susceptible and drug-resistant Gram-positives and fastidious Gram-negatives.
Competitive Advantages of APY409/461
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-positive and fastidious Gram-negative pathogens relevant to lower-respiratory-tract and skin-and-soft-tissue infections, including drug-resistant, multi-drug-resistant, and pan-drug-resistant isolates
–broader coverage of Gram-positives and fastidious Gram-negatives than the current standard-of-care intravenous-only drugs vancomycin and daptomycin and the current standard-of-care oral drug linezolid
high oral availability
–oral dosing, enabling outpatient treatment
–intravenous dosing with oral stepdown, enabling inpatient treatment followed by outpatient treatment
high efficacy
–efficacy in mouse MRSA lung and thigh infection comparable to current drug linezolid