Panacos Pharmaceuticals Inc., a biotechnology company dedicated to developing the next generation of antiviral therapeutic products, has filed an Investigational New Drug (IND) Application with the US Food and Drug Administration (FDA) for the company's second-generation HIV maturation inhibitor, PA-1050040.
Following review by the FDA, the company intends to begin phase 1 clinical trials of this new agent in the first quarter of 2007.
Maturation inhibition is a new target discovered by Panacos scientists and their academic collaborators. The first-in-class HIV maturation inhibitor, bevirimat (PA-457), has shown significant anti-HIV activity in HIV patients and is in phase 2b clinical testing. The company's second-generation maturation inhibitor program is designed to identify analogs of bevirimat with different pharmacological properties. Specific goals are to develop second-generation compounds that retain activity against HIV strains resistant to bevirimat, should these resistant strains appear in the clinic in the future.
In vitro studies with PA-1050040 have shown that the compound has a lower level of binding to human serum proteins than bevirimat, which may result in greater levels of free drug in patients dosed with the compound and thus the potential ability to inhibit HIV strains that exhibit partial bevirimat resistance. Furthermore, PA-1050040 retains wild-type activity against one of two bevirimat-resistant HIV isolates that represent the most-frequently mutated amino acids found by in vitro resistance-selection experiments performed to date.
These amino acids flank the HIV-1 capsid-SP1 cleavage site and the results suggest PA-1050040 may bind differently than bevirimat to this region of the viral Gag protein, which is the target for maturation inhibitor activity.
Graham Allaway, PhD, president and chief operating officer of Panacos commented, "Bevirimat, our first-generation maturation inhibitor, has shown the potential clinical value of maturation inhibitors. As the discoverers of this new HIV drug target, we intend to build a franchise in maturation inhibition. PA-1050040 represents one of a large number of second-generation maturation inhibitors currently in pre-clinical testing. We believe that maturation inhibitors have the potential to be important agents in the fight against HIV, and are pleased to be able to announce this step forward."
The current IND will allow Panacos to examine the pharmacokinetics of PA-1050040 following single doses in humans. The company intends to file additional INDs for other second-generation maturation inhibitors during 2007 and then select a candidate based partly on human pharmacokinetics to take into multiple dosing human clinical studies.