INV-88 Macrophage Migration Inhibitory Factor (MIF) Inhibitor

INV-88 is a novel class of proprietary oral MIF inhibitors discovered by Innovimmune using structure-guided drug design. INV-88 compounds specifically bind to MIF active sites leading to MIF conformational change and inhibition of MIF activity. MIF is a cytokine secreted by activated T cells and macrophages that plays an important role in autoimmune disease pathogenesis. MIF exerts its proinflammatory effects through its direct biological function and downstream signaling events following CD74/CD44 receptor engagement. The therapeutic utility in targeting MIF has been established, demonstrating preclinical efficacy in several autoimmune disease models including rheumatoid arthritis (1) and fibrosis.

Tumor cell- and immune effector cell-derived MIF are localized to exosomal, extracellular, cytoplasmic and intranuclear compartments. MIF activates MAPK and PI3K signal transduction, inhibits apoptosis, promotes angiogenesis, elicits premetastatic niche formation and resolves DNA replication stress; contributing to unperturbed cancer cell growth and metastasis. Strong evidence has demonstrated that MIF overexpression is implicated in increased proliferation, angiogenesis, and metastasis in these cancers and is a negative prognostic indicator associated with poor overall patient survival. Harnessing the long-established link between inflammation and cancer induction, Innovimmune’s INV-88 library of compounds has been adapted to disable MIF-mediated tumorigenesis. In preclinical studies, INV-88 lead compounds ameliorated tumorigenic phenotypes by perturbing proinflammatory responses and attenuating key pro-cancer signaling networks in multiple cell-based cancer models. The therapeutic anti-tumor effects of INV-88 has been established in preclinical tumor models (2).

Lead development efforts of novel chemical scaffolds of the INV-88 portfolio have advanced to final Lead Optimization ready to enter IND-enabling stage phase. Oral INV-88 MIF inhibitors have been designed with highly favorable physicochemical and ADMET properties that would translate into next-generation immunomodulatory therapies with a higher potency, better efficacy, superior safety profile and a wider therapeutic index providing better patient treatments.

References:

(1) 2014 American College of Rheumatology Annual Meeting (Boston, MA, USA) November 14-19, 2014

(2) 2022 American Association for Cancer Research Annual Meeting (New Orleans, LA, USA) April 8-13, 2022