Images are courtesy of Advanced Optical Microscopy Unit, Humanitas Research Labs, Istituto Clinico Humanitas.

Science

Developing a New Class of Cancer Immunotherapies

Macrophage Repolarization

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. Our macrophage repolarizing monoclonal antibodies trigger natural biological switches that transform immuno-suppressive M2-like macrophages into pro-inflammatory, anti-tumorigenic macrophages. These M1-like macrophages not only kill tumor cells, but also set in motion a cascade of signaling molecules that attract and turn on other cancer-fighting immune cells in the tumor microenvironment.

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By targeting tumor-associated macrophages, which are present in the majority of human cancers, Verseau aims to significantly expand the therapeutic benefit of immunotherapy. Unlike T-cells, tumor-associated macrophages are present in the majority of cancer indications and in the majority of cancer patients.

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

In patient-derived primary tumor ex vivo studies, our macrophage repolarizing monoclonal antibodies demonstrated a greater inflammatory response compared to current T-cell-targeting therapies in both PD-1 responsive and non-responsive tumor samples. In addition, in other assays and in in vivo studies we have shown that anti-tumor activity was enhanced when macrophage repolarizing mAbs were combined with current immunotherapies.

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Verseau’s Macrophage Repolarization Target Discovery Engine

Verseau utilizes a clinically focused discovery process, leveraging human biology to identify and validate novel macrophage repolarizing drug targets. In particular, our discovery engine combines a deep understanding of macrophage biology along with computational analysis to discover targets in silico using cancer patient genomic data. After in silico discovery, nominated 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 20 novel macrophage drug targets. Lead selection, preclinical proof of concept, and mechanism of action is then established by using human primary cell assay systems, patient-derived human tumors, as well as humanized and syngeneic mouse models. Verseau continues to weave in additional computational analysis throughout the development path to inform translational studies and maximize the potential success of our clinical development efforts.

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