AFN–1252 Anti-Staphylococcal Program
AFN-1252 is Affinium's lead clinical candidate selected from over 1,700 compounds in Affinium's staphylococcal inhibitory FabI library. Affinium recently completed the first oral Phase 2 clinical study of AFN-1252 in Acute Bacterial Skin and Skin Structure Infections (ABSSSI) due to staphylococci, conducted in accordance with current FDA guidance, which demonstrates successful proof of concept of efficacy and safety in man. Phase 1 clinical trials of an intravenous formulation are scheduled for 2013.
Key properties of AFN-1252 include:
- Clinical cure rates of >93% with the oral formulation in Phase 2 ABSSSI due to staphylococci.
- Excellent clinical and pre-clinical safety profile.
- Once daily oral dosing is anticipated.
- New small-molecule entity with a new mechanism of action.
- First-in-class FabI agent.
- No inhibition of relevant human target.
- Unique, targeted anti-staphylococcal spectrum of activity.
- Highly potent inhibitory activity against staphylococci (S. aureus FabI IC50 of 14 nM).
- Extremely low MIC90 of 0.016 µg/ml against >2400 strains of staphylococci including MRSA, VISA, VRSA, LRSA, and all other drug resistance mechanisms tested.
- Excellent oral efficacy in multiple mouse models of infection including thigh abscess, subcutaneous abscess, subcutaneous granuloma pouch, pneumonia and peritonitis / septicemia models; 3-20 times more efficacious than linezolid.
- Low propensity for resistance development in both single step and multiple passage selection experiments.
- No antagonism with any known antibiotic class and synergy with several antibiotic classes.
By specifically targeting staphylococci, and not disrupting the human microbiome, AFN-1252 is positioned to have significant safety advantages as its use is expected to result in much reduced selection pressure for overgrowth of antibiotic resistant organisms (e.g. C. difficile, VRE), and in much less diarrhea, colitis, C.difficile infections and candidiasis.
AFN-1252 co-crystallized in the S. aureus FabI enzyme
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