Maturation Inhibitors

1
Maturation Inhibitors

• Bevirimat (BVM, formerly PA-457) first in class
  maturation inhibitor-
• Maturation inhibitors inhibit the conversion of
  p25 (CA-SP1) to p24 (CA), yielding non infectious
  virions.
• BVM is currently in Phase 2B clinical trials

• A 2nd generation maturation inhibitor
• Retain BVMs attractive profile
• Once daily oral administration
• No drug interactions
• Safe and well tolerated
• A distinct resistance profile
• Reduced serum protein binding

2
PA1050040, a 2nd generation maturation inhibitor

• PA1050040 is a chemical analog of BVM
• Inhibits virus replication by the same mechanism
  of action
• Potent inhibitor of primary and prototypic HIV-1
  isolates with an IC50 15 nM
• Wild-type activity against HIV isolates resistant
  to all four classes of approved drugs
• Wild-type activity against the BVM-resistant
  isolate, L363M
• Reduced protein binding, free fraction 8-15 fold
  greater than BVM in serum shift assays
• Favorable pre-clinical pharmacokinetic and
  metabolic profile
• Entered Phase I single dose clinical trial