Many currently available therapies for autoimmune disease are marked by low remission rates and limited duration of efficacy, leading to inadequate control of disease for many patients. Treatments may also result in significant side effects and safety issues, including global immune suppression, making them poor options for long-term treatment, early stage intervention, or use in combination therapy. Over time, persistent autoimmune disease can cause patients to develop serious and life-threatening complications such as fibrosis, for which very few therapies are available.
Lycera’s novel immune suppressor portfolio positions the company to have a significant impact in treating autoimmune disease. The Company’s programs originate from several important areas of research, including immune metabolism, cell signaling, and immune cell differentiation, and are anticipated to dampen or suppress auto-immune reactions. These agents have been shown to be beneficial in several widely-accepted models for autoimmune disease, as well as in human translational systems, acting through pathways directly involved in immune regulation.
Lycera’s lead immune suppression program originates from our deep expertise in immune metabolism, a field of biology focused on how energy is made and utilized. Unlike normal cells, disease-causing immune cells have metabolic abnormalities that sensitize them to modulation of the mitochondrial enzyme F1F0-ATPase. Lycera has developed proprietary compounds targeting this enzyme in order to selectively induce cell death (apoptosis) of chronically activated disease-causing immune cells, while sparing normal immune cells that fight infection. ATPase modulators are unique, first-in-class drugs with the potential to treat a broad spectrum of conditions.
Publications for ATPase Modulators
Digestive Disease Week 2014 (Presentation). Modulation of the F1F0-ATPase Induces Apoptosis of Mouse and Human Lamina Propria T-cells and Is Efficacious in Models of IBD. Luigi Franchi, Ivan Monteleone, Rodney Morgan, Anthony W. Opipari, Laura Carter, Gary Glick, Giovanni Monteleone
Digestive Disease Week 2014 (Poster). F1F0-ATPase Modulation Is Efficacious in Models in IBD and Induces Apoptosis of Human CCR9+ Gut-Tropic T-cells. Luigi Franchi, Kelan A. Hlavaty, Ivan Monteleone, Rodney Morgan, Kelli Porzondek, Brian Sanchez, Charles Lesch, Mark A. Spahr, Corrin Hepburn, Anthony W. Opipari, Giovanni Monteleone, Gary Glick, Laura Carter, Peter D. Higgins
E. Gatza, D.R. Wahl, A.W. Opipari, T.B. Sundberg, P. Reddy, C. Liu, G.D. Glick, J. L.M. Ferrara. “Manipulating the bioenergetics of alloreactive T cells causes their selective apoptosis and arrests graft versus host disease,” Science Translational Medicine, 2011; 3: 67ra8.
D.R. Wahl, B.Petersen, R. Warner, B.C. Richardson, G.D. Glick, A.W. Opipari. “Characterization of the metabolic phenotype of chronically activated lymphocytes,” Lupus, 2010; 19: 1492.