PHARMACODYNAMIC (PD)

Agilex Pharmacodynamics Services

Pharmacodynamics (PD) is the study of the biochemical, physiological and molecular effects of a therapeutic on the body. PD assessments provide vital information on the receptor binding, pathways, genes, RNA and proteins modulated by therapeutics during a clinical or preclinical study, providing vital efficacy assessments to help investigators refine and optimize dosing schedules to achieve therapeutic effectiveness.

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At Agilex Biolabs, we have extensive experience across a range of assays and platforms to enable sponsors to assess the effects of their therapeutic on the immune system (immunogenicity, immune cell modulation, immunophenotyping, proliferation, activation and receptor occupancy), cellular biomarkers (cytokines, chemokines and other inflammatory markers) and molecular markers (DNA and RNA). Our Pharmacodynamics services include:

  • Immunogenicity
  • Vaccines
  • Cell-based Immunology assays
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Immunogenicity

Immunogenicity refers to the ability of a biotherapeutic to induce a humoral or cellular immune response. These responses can either be desirable, such as those generated by vaccines which are designed to provide a protective immune response, or undesirable in the case of anti-drug antibodies, which can bind to the therapeutic and promote its clearance thereby reducing its efficacy.

Scientific Expertise

The Agilex Scientific team have a deep understanding of immunogenicity assessment for biologics, with an in-depth knowledge of developing and validating drug and target tolerant assays to meet the needs of the study and in accordance with the latest regulatory requirements (EMA and FDA). Experience across ELISA and MSD platforms, including standard bridging assays (with and without acid), solid phase extraction with acid dissociation, affinity capture elution assay formats and precipitation and acid dissociation assays for oncology studies requiring high drug and target tolerance.

Agilex offers a comprehensive tiered approach for immunogenicity assessment, including:

  • Screening Assays
  • Confirmatory Assays
  • Titer Assays
  • Neutralizing antibody assays
  • Neutralizing antibody assays
  • Customized cell-based assays
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Vaccines

Agilex offers a comprehensive suite of services to support vaccine development, including customized immunoassays, molecular and flow cytometry assays that support the advancement of novel vaccine studies.

Scientific Expertise

The Agilex Scientific team have a deep understanding of antigen-antibody responses and developing, qualifying and validating custom vaccine-specific immunoassays (ELISA/MSD) to detect vaccine-specific antibodies, antibody subtyping, ELISpot enumeration of specific T-cell and B-cell responses, customized cell based assays, neutralizing antibody assays and molecular assays.

Assays supported

  • Vaccine-specific ELISA/MSD Immunoassay
  • IgM, IgG subtyping
  • PBMC isolation
  • ELISpot assay
  • Flow cytometry
  • Biomarker assay (ELISA, MSD, ELISpot)
  • Custom molecular assays (qPCR, qRT-PCR, digital PCR)
  • Hemagglutination inhibition assays (HAI)
  • Custom cell based immunology assays
  • Custom ligand binding and cell-based neutralizing assays
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Cell based immunology Assays

Agilex offers a comprehensive suite of solutions for immunology, including ELISpot, flow cytometry, proliferation, activation, cytokine release assays and customized cellular and molecular assays to inform the pharmacodynamics of the drug discovery program.

ELISpot

ELISpot is widely used in preclinical and clinical immunological assessments due to its high sensitivity, specificity, and ability to detect rare immune cell responses. The assay quantifies antigen-specific T-cell or B-cell responses by capturing secreted cytokines or antibodies. This capability is crucial for assessing the mode of action, efficacy and safety of new therapeutics, especially in immuno-oncology, vaccine development, and autoimmune disease treatments.

At Agilex, ELISpot is frequently employed in different stages of clinical trials to assess immune responses therapeutics by measuring the number of cytokine-secreting cells in PBMCs or whole blood at a single cell level.

Assays Supported

Vaccines

In vaccine trials, ELISpot is used to measure antigen-specific B-cell or T-cell responses, providing early indicators of immunogenicity and potential protective immunity.

Autoimmune Disease Monitoring

In autoimmune diseases, ELISpot assays detect aberrant immune activation and assess the efficacy of immunosuppressive or immunomodulatory drugs.

Magnetic Bead-Based Cell Sorting

Magnetic bead-based sorting relies on antibodies conjugated to magnetic beads that selectively bind to surface markers of target cells. A magnetic field is then applied to separate labeled cells from the rest of the population. This method allows for the enrichment of highly specific immune cell subsets, such as CD4+ and CD8+ T cells, B cells, monocytes, and dendritic cells.

Immuno-Oncology

For cancer immunotherapies, such as checkpoint inhibitors and adoptive T-cell therapies, ELISpot helps in determining whether a patient’s immune system is capable of mounting an effective response against tumor antigens.

Isolation of Immune Cells Using Magnetic Sorting Beads

To perform ELISpot effectively, high-purity immune cells are required. Magnetic-activated cell sorting (MACS) is a widely used method for isolating discrete immune cell populations from whole blood or peripheral blood mononuclear cells (PBMCs). The use of magnetic sorting beads enables rapid, high-yield, and high-purity isolation of specific immune subsets, ensuring accurate downstream functional analyses.

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Flow Cytometry

Flow cytometry is a powerful tool to enable the quantitation of single cells or particles. The power of Flow cytometry lies in its ability to multiplex different markers on the surface of or internally within a single cell at the same time being able to quantify lineages of cells within whole blood in order to provide profiling and immunophenotyping analyses. Using state-of-the-art multi-laser flow cytometers, Agilex Scientists can identify changes in cell populations during a clinical study as well as provide critical PD assays, including cell phenotyping, target engagement and receptor occupancy assays and identify granular changes within a single cell in response to treatment.

Flow cytometry is a powerful tool to enable the quantitation of single cells or particles. The power of Flow cytometry lies in its ability to multiplex different markers on the surface of or internally within a single cell at the same time being able to quantify lineages of cells within whole blood in order to provide profiling and immunophenotyping analyses.

Scientific Expertise

Our Scientists have published extensively in the areas of inflammation and immunology using flow cytometry and have extensive expertise and experience across multiple assay types (cellular proliferation and activation assays, receptor occupancy assays and immunophenotyping assays) to develop and validate custom fit for purpose assays based on your needs.

Dedicated Flow Cytometry Laboratories in Australia for Fast Turn Around of Data

With dedicated Flow Cytometry laboratories co-located within dedicated Phase 1 units as well as at our Headquarters in Adelaide, Australia, Agilex can support real-time sample processing and flow cytometry analysis.

State-of-the-Art Equipment

Agilex has state-of-the-art BD FACSymphony® A3, five laser, twenty colour instruments as well as three laser Cytek® Aurora spectral flow cytometers to enable flexibility, deliver high resolution data, exceptional sensitivity and provide fast sample analysis.

Assays Supported

  • Receptor occupancy and target engagement
  • Activation and proliferation assays
  • Immunophenotyping and cell enumeration
  • Ex vivo simulation and Cytokine release assays
  • Ex Vivo Stimulation and Functional assays
  • Signa transduction pathway analysis
  • Apoptosis and cell death assessment
  • Minimal residual disease detection
  • Biomarker assays
  • Customized cell-based assays

World class technology