ROR1 targeting is fundamental to NovalGen’s first three lead programmes. To enhance potency, we have developed a panel of ROR1 binding antibodies that target different epitopes.
Many other ROR1-targeting antibodies bind the Ig domain. However, NovalGen remains the only clinical stage company that can target the Frizzled domain - the binding site for many ROR1 ligands (e.g. WNT-5). Our Frizzled-targeting antibody is able to antagonise signalling. Additionally, as the Frizzled domain is membrane-proximal, it provides a more efficacious targeting epitope for T cell engagers and CAR-T cells, leading to more efficient immune synapse formation.
NovalGen’s panel of ROR1 antibodies can be applied to multiple formats for both therapeutics and analytics. These include T cell engagers, antagonistic monoclonal antibodies, antibody drug conjugates (ADCs), antibody-dependent cellular cytotoxicity (ADCC) enhanced antibodies, CAR-T, and antibodies for immunohistochemistry and flow cytometry. This provides NovalGen with a wide ranging toolbox for targeting ROR1 which is over expressed on many hard to treat malignancies.
NovalGen has developed T cell engagers (TCEs) that build on our ROR1-binding antibodies (e.g. NVG-111). These off-the-shelf therapies redirect the body’s own natural cancer defence, the immune system, to eradicate tumor cells.
When NVG-111 binds CD3 on the surface of a T cell and the Frizzled domain of ROR1 on a tumor cell, the T cell is activated, leading to the formation of an immune synapse with the tumor cell followed by the release of cytotoxic molecules to kill the tumor.
NovalGen has engineered our proprietary T cell engagers to enable the optimal distance for synapse formation to be achieved. This, combined with targeting the membrane proximal Frizzled domain, allows for greater efficiency in immune synapse formation, enhancing the cytotoxic efficacy of our TCEs.
NVG-111, which is in clinical development, has a small molecular format and is delivered by continuous infusion that enables the maintenance of high steady-state plasma concentrations and rapid elimination of drug following treatment cessation.
NVG-222 is a next generation half-life extended TCE that builds on the success of NVG-111. It maintaining the optimal distance for synapse formation to induce cytotoxic activity, whilst providing weekly dose administration. Built into NVG-222 is proprietary autoregulation technology that enhances safety and the therapeutic window for this First-in-class T cell engager.
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NovalGen’s proprietary ground-breaking autoregulation technology platform enables the maximum efficacy to be unleashed from a therapy whilst ensuring a manageable safety profile by limiting life threatening toxicities.Read more
Novalgen is a fully integrated company capable of developing breakthrough therapies.Read more