Preclincal Testing

Early Lead Identification and Optimization

The discovery of novel drug compounds effective against human immunodeficiency virus (HIV) requires experience and technology that extends beyond the capabilities of most clinical laboratories. Monogram has the tools and expertise to help pharmaceutical and biotech companies optimize their preclinical and clinical drug development programs through early lead drug identification, lead candidate selection, and characterization throughout clinical development.

PhenoSense® and PhenoScreen™ technologies provide a better understanding of a novel compound’s potential benefits based on its activity against a wide range of real-world viruses and specific mutational patterns, as compared with other drugs in the same class.

Monogram can also build site-directed mutants (SDMs) and incorporate them into a panel of viruses to be tested against a set of novel compounds.

Novel drug testing services include access to Monogram's scientists for study design and data interpretation.

Novel Drug Evaluations

Monogram Biosciences’ novel drug testing utilizes all of the PhenoSense HIV assays designed to evaluate the activity of protease (PR), reverse transcriptase (RT), integrase inhibitors (INIs), or entry inhibitors and to measure changes in drug susceptibility of patient viruses to these inhibitors. The novel drug testing assays can help evaluate cross-resistance in HIV-1 with reduced susceptibility to US Food and Drug Administration (FDA)-approved drugs by using either patient-derived viruses from Monogram’s library or viruses (present in patient plasma or tissue culture supernatants or other sources) supplied by the client. The extent of cross-resistance can be a preliminary indicator of the possible utility of the novel compound(s) for treatment of patients. Novel compounds undergo preliminary testing to determine the optimal start concentration and drug dilutions to use in the assay to achieve maximum accuracy and reproducibility. Testing and data analysis are conducted under standard laboratory procedures in Monogram’s CLIA-certified and CAP-certified clinical reference laboratory.

Monogram can also build site-directed mutants (SDMs) and incorporate them into a panel of viruses to be tested against a set of novel compounds.

PhenoSense® Customized Novel Drug Testing/Resistance Characterization

  • The most precise and extensive assessment of drug susceptibility for identified drug candidates
    • State-of-the-art PhenoSense assay format
    • Fully customized virus panels
    • Highly accurate IC50 values and fold changes relative to control viruses
    • Addresses pre-IND and clinical trial regulatory requirements

Drug profiling: As part of the novel drug offering, clients also have the option to include their novel compound in Monogram’s standard PhenoSense PR/RT panel during routine clinical lab testing. The novel drug data are reported only to the submitting client along with the daily PhenoSense results, thereby providing a direct comparison of the novel compound to all commercially available drugs.

 

PhenoScreen™ Novel Drug Screening

Monogram Biosciences’ PhenoScreen is a phenotypic screening assay designed to evaluate the activity of reverse transcriptase (RT), integrase, or entry inhibitors in a high-throughput fashion. At this time, it is not possible to evaluate protease inhibitor compounds with PhenoScreen. This assay is an economical way to screen many compounds (typically greater than 25) against a small panel of well-characterized library viruses. The virus panel, which is selected based on client’s requirements, consists of 5 to 20 viruses and is used repeatedly for all compounds tested. The reported data consist of IC50 and fold change values compared to a wild-type reference HIV-1 virus and susceptibility curves for each drug/virus combination.

PhenoScreen High-Throughput Novel Drug Screening

  • Optimal method for evaluating large numbers of candidate compounds
    • Rapid testing of 10 to hundreds of compounds
    • Drug activity assessed against a panel of drug-sensitive and multidrug-resistant viruses
    • Approximate IC50 values and fold changes relative to control viruses
    • Cost-efficient method for preclinical development

Click here to download slide presentation featuring vector and transfections schematics.