LEVERAGING NEW INSIGHTS
INTO IMMUNE METABOLISM
Recent discoveries in immune metabolism enable us to intervene precisely to block specific cells at the root of gut inflammation. We aim to stop flare-ups with our MetaWaveTM therapies. Here's how:
IBD is driven by pathogenic Th17 cells. They rely on a cellular process called oxidative phosphorylation to survive.
A Therapeutic Disruption
Our MetaWave therapies are designed to disrupt oxidative phosphorylation in the mitochondria of pathogenic Th17 cells. The therapies are highly specific, targeting just those cells that play a role in IBD.
By killing Th17 cells, MetaWave reduces inflammation, calming the gut. Healthy cells remain untouched.
The MetaWave Advantage
We’re on a mission to disrupt the frustrating cycles of IBD. Current therapies simply do not work for many people living with mild-to-moderate and moderate-to-severe IBD, leaving them to try one intervention after another, all the while enduring chronic symptoms that dramatically reduce their quality of life.
There is also substantial unmet need among people who develop immune related colitis as a result of cancer immunotherapy with checkpoint inhibitors. They find themselves in a painful dilemma: The few medications available to treat their colitis have the unfortunate side effect of reducing the efficacy of their cancer treatment. If their physician prescribes higher doses of the checkpoint inhibitor, they risk exacerbating their colitis.
Drawing on our translational biology, process development and manufacturing expertise, we are creating proprietary forms of niclosamide – an FDA-approved drug that works by disrupting oxidative phosphorylation – to address patient needs at all stages of IBD, from mild to severe, and for cancer patients with checkpoint-induced colitis.
Our therapies are designed to rapidly halt or delay the progression of disease, stopping flare-ups and driving the disease into sustained remission. Promising early data show our MetaWave therapies selectively kill pathogenic, inflammatory cells while leaving healthy cells untouched.
By thinking differently about IBD, we hope to improve the lives of millions.
The field of immune metabolism is advancing rapidly. We are building on – and contributing to – a growing body of scientific literature.
Shin, B., Benavides, G. A., Geng, J., Koralov, S. B., Hu, H., Darley-Usmar, V. M., & Harrington, L. E. (2020). Mitochondrial oxidative phosphorylation regulates the fate decision between pathogenic Th17 and regulatory T cells. Cell Reports, 30(6), 1898-1909. doi:10.1016/j.celrep.2020.01.022. Read more.
Fuseini, H., Cephus, J., Wu, P., Davis, J. B., Contreras, D. C., Gandhi, V. D., Rathmell, J. C., & Newcomb, D. C. (2019). ERα signaling increased IL-17A production in Th17 cells by upregulating IL-23R expression, mitochondrial respiration, and proliferation. Frontiers in Immunology, 10. doi:10.3389/fimmu.2019.02740. Read more.
Kaufmann, U., Kahlfuss, S., Yang, J., Ivanova, E., Koralov, S. B., & Feske, S. (2019). Calcium Signaling Controls Pathogenic Th17 Cell-Mediated Inflammation by Regulating Mitochondrial Function. Cell Metabolism, 29(5), 1104-1118. doi:10.1016/j.cmet.2019.01.019. Read more.
Franchi, L., Monteleone, I., Hao, L., Spahr, M. A., Zhao, W., Liu, X., Demock, K., Kulkarni, A., Lesch, C. A., Sanchez, B., Carter, L., Marafini, I., Hu, X., Mashadova, O., Yuan, M., Asara, J. M., Singh, H., Lyssiotis, C. A., Monteleone, G., Opipari, A. W., & Glick, G. D. (2017). Inhibiting oxidative phosphorylation in vivo restrains Th17 effector responses and ameliorates murine colitis. The Journal of Immunology, 204(2). doi:10.4049/jimmunol.1600810. Read more
Tao, H., Zhang, Y., Zeng, X., Shulman, G. I., & Jin, S. (2014). Niclosamide ethanolamine improves blood glycemic control and reduces hepatic steatosis in mice. Nature Medicine, 20(11), 1263-1269. doi:10.1038/nm.3699. Read more