Our Science

Modulating Immune Function

Our bodies respond to inﬂammatory stimuli (like a pathogenic infection) with a protective inﬂammatory cascade. This inflammatory response is tightly regulated by molecular mechanisms involving circulating antibodies, which can re-establish homeostasis after an infection clears. Antibodies can be either pro-inflammatory or anti-inflammatory depending on a switch located on a specific part (Fc domain) of immunoglobulin G (IgG) antibodies. When antibodies are coated with a sugar group (sialylation), they can bind to Type II Fcγ receptors, which returns the immune environment to an anti-inflammatory (tolerant or vigilant) state.

Autoimmune patients have low sialylation during periods of symptom worsening (inflammation), and consequently have heightened proinflammatory responses.

Immune homeostasis is re-established with high-dose IVIg, which contains a small fraction of sialylation (5-15% of the total IgG) present in this blood-based product. Pre-clinical and clinical studies have shown that use of IVIg for reducing the autoimmune symptoms is strictly dependent on the presence of the sialylated fraction of IgGs binding to Type II Fcγ receptors.

Limitations of IVIg Immune Modulation

IVIg immune modulation is effective in treating autoimmune diseases, but is limited by supply & preparation as a blood product therapy with inherent safety risks and narrow therapeutic window.

Limitations of Immunosuppression

Most autoimmune therapies suppress immune function, which can poke holes in the immune system's defense shield, presenting significant infection risks to patients.

NVG-2089

NVG-2089 triggers our bodies’ endogenous regulatory mechanisms to reduce autoimmune dysregulation without immunosuppression. NVG-2089 is designed to mimic the binding of sialylated IgG to immunomodulatory Type II Fcγ receptors. A Phase 1 clinical study demonstrated the safety and tolerability of NVG-2089 in healthy volunteers.

Upregulates the inhibitory immune checkpoint FcγRIIB on B cells & myeloid cells, leading to a negative regulation of function

Expands Tregs to suppress effector T function

Binding of NVG-2089 to Type II FcγRs leads to downstream mechanisms that reduce the dysregulated inflammatory response:

Our Platform

At Nuvig, we incorporate our engineered Fc into full-length antibodies to create bi- and tri-functional antibodies. We call this BESTech™ (Biologic Enhancement of Self Tolerance).

In preclinical experiments we observed substantially enhanced efficacy with the combination of our BESTech Fc and an anti-cytokine variable region (e.g. together, a BESTech mAb) vs. the wild-type antibody. We believe BESTech can be applied to multiple anti-inflammatory targets.

Publications & Presentations

Publication

Sneed SL, et al. (2024) An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with i.v. immunoglobulin. Published in Journal of Clinical Investigation.

Presentation

Sneed SL, et al (2024) An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with IVIG. Presented at Keystone Symposia’s Antibodies as Drugs: The Art in Antibody Engineering. View Abstract.

Our Pipeline

See our therapeutic areas.

Pipeline