Science

Developing First-in-Class Macrophage Checkpoint Modulators (MCMs)

Macrophage Checkpoint Modulators

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Verseau is broadening the therapeutic potential of immunotherapy by targeting macrophages, the master orchestrators of the immune system. Macrophages can adopt different functional roles in response to signals from their environment, including the ability to direct pro-inflammatory and anti-inflammatory immune responses. Our macrophage checkpoint modulators (MCMs) can reprogram macrophages to be more inflammatory or more tolerogenic depending on the disease context. Verseau’s MCMs are being developed as treatments for cancer as well as inflammatory and immune (I&I) diseases.

As a potential therapeutic for cancer, our MCMs generate a coordinated and robust anti-tumor response by switching macrophages to a more active and inflammatory state, activating T cells and recruiting other immune cells.

A Platform to Identify and Validate Novel Macrophage Targets

Verseau utilizes an all-human translational platform to identify and validate novel drug targets that play an important role in harnessing an immune response. The targets that we have identified are exclusive to immune cells, which may translate to an enhanced safety profile in the clinic. They are present in the majority of cancers, including those cancers that are non-responsive to current checkpoint inhibitors, and engage several diverse biological pathways. Our drug development programs based on these novel targets have the potential to be first-in-class therapeutics that may transform care for patients.

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Verseau combines a deep biological understanding of myeloid cells along with computational analysis to discover targets in silico using patient genomic data. After in silico discovery, potential targets are validated by applying proprietary siRNA in lipid nanoparticle technology for specific target knockdown in primary human macrophages. As a result of this process, Verseau has identified and validated more than two dozen novel immune regulation drug targets and has a robust pipeline of multiple differentiated macrophage checkpoint modulator (MCM) monoclonal antibody programs. Preclinical proof of concept is established using patient-derived human tumors.

Macrophage-Targeting Cancer Immunotherapies

T cell-directed checkpoint inhibition works to boost the immune response against cancer by blocking the PD-1/PD-L1 binding that prevents T cells from attacking cancer cells. While many patients benefit from PD-1 inhibitor therapies, they are only effective in the 25% of cancers that involve T cell infiltration.

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By targeting modulation of macrophages, which are present in the majority of human cancers, Verseau aims to significantly expand the therapeutic benefit of immunotherapy. By conservative estimates, tumor-associated macrophages are present in 75%* of tumors. Tumor-associated macrophages can promote the survival, invasion, and metastasis of tumor cells; in addition, they can support tumor angiogenesis and inhibit the antitumor immune response mediated by T cells.

Verseau’s macrophage checkpoint modulators (MCMs) have a three-part mechanism of action for a coordinated immune attack on the tumor: 1) tumor microenvironment activation, 2) recruitment of naïve immune cells including T cells, and 3) activation of T cells.

In patient-derived primary tumors, our MCMs have demonstrated a greater inflammatory response compared to current immunotherapies in both PD-1 responsive and non-responsive tumors. In addition, anti-tumor activity was enhanced when MCMs were combined with current immunotherapies.

*Proprietary Genomic Analysis by Verseau: 10,000 cancer patients across 33 tumor types