Clinical Therapeutic Pipeline:
Immunoregulartory Drug Development Portfolio
Omilancor
Omilancor Exerts Anti-Inflammatory Effects Within the Gastrointestinal Tract
Omilancor is a first-in-class, gut-restricted, oral once-daily Phase 3-ready therapeutic designed to address the limitations of current ulcerative colitis (UC) and Crohn’s disease (CD) therapies by providing once a day oral dosing, low systemic exposure, and improved tolerability with limited to no toxicity.
Omilancor works by targeting LANCL2, a membrane receptor that modulates immunological mechanisms associated with UC and CD, to generate suppressive regulatory CD4+ cells (Tregs) that work directly at the site of inflammation to restore and maintain immune tolerance in the GI tract.
Lanthionine Synthetase C-Like 2 (LANCL2) is a multipronged mechanism of action targeting known downstream immunological targets tied to autoimmune diseases, including ulcerative colitis and Crohn’s disease
By targeting LANCL2, omilancor generates suppressive regulatory CD4+ T cells (Tregs) that restore and maintain immune tolerance in the GI tract:
- Enhances CD25/STAT5 signaling to support the stable differentiation of regulatory CD4+ T cells with greater anti-inflammatory functionality
- Increases pyruvate dehydrogenase (PDH) activity, resulting in increased oxidative metabolism supporting FOXP3 stability
- Increases suppressive effects of Tregs due to enhanced immune checkpoint surface markers (LAG3 and PD-1)
Omilancor was previously evaluated for the treatment of UC in a Phase 2 randomized, placebo-controlled clinical trial that demonstrated gut-restriction, biologic-like efficacy, and potentially best-in-class safety. Based on these findings and positive correspondence with the U.S. Food and Drug Administration (FDA), NImmune plans to initiate a Phase 3 randomized, placebo-controlled clinical trial in 2023.
A summary of the Phase 2 omilancor data can be found in NImmune’s corporate presentation.
NIM-1324
NIM-1324 Exerts Anti-Inflammatory Effects Systemically Throughout the Body
NIM-1324 is a Phase 2-ready once-daily, oral, systemically distributed LANCL2 agonist designed to reduce inflammatory cell infiltration with less toxicity than current standard of care, including biologics and JAK-inhibitors.
In preclinical models of SLE and RA, NIM-1324 has demonstrated the ability to induce enhanced regulatory T cell (Treg) function and reduce interferon gamma signaling in human peripheral blood mononuclear cells. Additionally, in multiple mouse models of lupus, oral treatment with NIM-1324 maintained kidney function, reduced anti-nuclear antibody formation and shifted the balance of CD4+ T cells from effector or inflammatory subsets to protective Tregs in the spleen. In animal models of RA, activation of the LANCL2 pathway by NIM-1324 resulted in decreased tissue-damaging Th17 and Tfh cells with increased protective Tregs.
NIM- 1324 successfully completed a Phase 1 randomized, double-blind, placebo-controlled multi-cohort study evaluating its safety, tolerability, and pharmacokinetics (PK) in normal healthy volunteers where all endpoints were met and is now ready for further clinical testing in lupus and RA patients.