Eyevinal (ibudilast)

P1/2, N=50, Active, not recruiting, MediciNova | Trial completion date: Jun 2024 --> Dec 2024

P2, N=36, Completed, MediciNova | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2024

P2, N=120, Recruiting, VA Office of Research and Development | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2/3, N=230, Recruiting, MediciNova | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2/3, N=230, Recruiting, MediciNova | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=50, Active, not recruiting, MediciNova | Phase classification: P1b/2a --> P1/2

P2, N=120, Recruiting, VA Office of Research and Development | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P2/3, N=230, Recruiting, MediciNova | Phase classification: P2b --> P2/3

We have shown that partial (p)MHC class II constructs (i.e., Recombinant T-cell receptor Ligand - RTL1000), comprised of the extracellular α1 and β1 domains of MHC class II molecules linked covalently to myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, can address the neuroimmune effects of methamphetamine addiction through its ability to bind to and down-regulate CD74 expression, block macrophage migration inhibitory factor (MIF) signaling, and reduce levels of pro-inflammatory chemokine ligand 2 (CCL2). Post hoc tests indicated that mice treated with methamphetamine and DRmQ or ibudilast had significantly lower levels of MIP-2 in frontal cortex, as compared to mice treated with methamphetamine and vehicle (p > 0.05). By specifically targeting CD74, our DRQ constructs can block the signaling of MIF, inhibiting the downstream signaling and pro-inflammatory effects that contribute to and perpetuate methamphetamine addiction.

CD3 expression was a good predictor for tumor progression for five months in recurrent GBM patients treated with MN-166 and TMZ. T cell infiltration within GBM tumors has been an active area of research with the success of immune checkpoint blockade (ICB) therapies in other cancers. Moreover, MN-166 has been shown to impact immune suppressive myeloid cells, which are linked to the immune suppressive tumor microenvironment and a resistance mechanism to ICB.

Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.

Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting.