AIDS
PL-100: A New HIV Protease Inhibitor Shows Most Favorable Cross-Resistance Profile,a comparative study
By Akanksha, Pharmacology Correspondent
Feb 4, 2005, 09:22

Procyon Biopharma Inc.,reported today that it has completed a larger viral cross-resistance study in collaboration with the ViroLogic Inc.to compare the resistance profile of its lead HIV protease inhibitor PL-100 with commercially available protease inhibitors (PIs).The results showed that PL-100 and its back-up analogue PL-337 had the most favorable cross-resistance profile of all the PIs studied as measured by the median fold change in IC50 as well as percentage of the strains requiring a fold-change of the drug greater than either 2.5 or 10 as described below.

The current study report was based on 63 HIV resistant strains including the 14 resistant strains that were part of the panel reported previously by Procyon in November 2003.

The selected viral strains were challenged with PL-100 and PL-337 and the commercially available PIs, amprenavir(APV),indinavir(IDV),lopinavir(LPV),nelfinavir(NFV), saquinavir(SQV),the recently available PI,atazanavir (ATV).In addition the viral strains selected for the
study also contained important resistant mutations for two other PIs currently in clinical studies by pharmaceutical companies.These strains were found to be susceptible to both PL-100 and PL-337.

"We are very pleased with the latest cross-resistance results showing that in a larger panel of resistant HIV viral isolates,PL-100 and PL-337 performed better than the currently-approved protease inhibitors," said Hans Mader, President and Chief Executive Officer of Procyon Biopharma Inc. "This confirms the competitive uniqueness of PL-100 and this together with the pharmacokinetic profile that we expect to obtain very soon will allow us to move PL-100 into human clinical studies later this year," he added.

The study described the unique resistance profile of PL-100, as assessed by in vitro susceptibility testing with a reporter-gene based phenotypic assay in comparison with six currently-marketed protease inhibitors.

The fold change (FC) in IC50 (50% inhibitory concentration) required to overcome resistance was determined for each PI. Arbitrary cut-offs of 2.5, 10 and 50 were adopted. Strains that required a fold-change below 2.5 were considered to be fully sensitive to drug while strains requiring a fold-change between 2.5 and 10 were considered to display low-level resistance to drug.Strains requiring a fold-change over 50 were deemed to be highly resistant to the drug.

On average, PL-100 and PL-337 showed significantly better antiviral activity than the approved protease inhibitors tested.This indicates the potential for good activity against existing protease inhibitor-resistant virus in treatment-experienced patients or in those patients newly-infected with drug-resistant strains with similar patterns of PI mutation.

"ViroLogic's results with the 63 resistant strains clearly confirm the robust resistance profile of Procyon's drug candidates PL-100 and PL-337,"said Professor Mark Wainberg, Director of McGill University AIDS Centre."This in addition to the forced resistance studies which have been ongoing for six months in our laboratories to assess potential mutations arising against PL-100, give us confidence to move forward with the clinical development of this very promising compound."

The Company is currently completing preclinical work and expects to file an Investigational New Drug (IND/CTA) submission during the second half of 2005 in order to commence a human clinical Phase I trial shortly thereafter.

PL-100 has potent anti-protease and antiviral activity against wild-type HIV-1 and has a favorable cross-resistance profile as compared to currently-marketed protease inhibitors namely: saquinavir,indinavir, nelfinavir, amprenavir,atazanavir and lopinavir.

This indicates the potential for good activity against existing protease inhibitor-resistant virus in treatment-experienced patients or in those patients newly-infected with similar resistant strains.
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ViroLogic is a biotechnology company committed to advancing individualized medicine by discovering, developing and marketing innovative products to guide and improve treatment
of serious viral, immunologic,and oncologic diseases.

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