Results were presented in a poster presentation entitled "Novel synthetic RORgamma agonist compounds as a potential anti-tumor therapeutic approach" and will be highlighted in an oral presentation on Saturday, November 8, at 1:40 PM.
The research findings demonstrate that RORgamma agonists reprogram immune cells to enhance their activity and survival as well as decrease immunosuppressive mechanisms in the tumor that can limit the efficacy of cancer immunotherapies.
Collectively, these activities result in decreased tumor growth and significantly enhanced survival in animal models of cancer. As a result, researchers conclude modulation of the immune system by RORgamma agonists may provide significant anti-tumor benefits in treatment of a range of cancers.
"While research involving immune-oncology approaches to treat cancer is expected to have a substantial impact in the years ahead, most agents in development are biologics with single mechanisms of action," said Gary Glick, Ph.D., founder and chief scientific officer, Lycera Corp., adding, "Lycera’s proprietary and wholly owned program based on RORgamma agonists represents a completely new approach that is shown to have multiple anti-cancer mechanisms."
According to the study results, RORgamma small molecule agonists effectively increase immune activation mechanisms, such as enhanced cytokine production from murine and human cells.
They also decrease immune suppression mechanisms as demonstrated by favorable changes in effector T cell to Treg cell ratios and by reduced PD-1 expression and cell desensitization to checkpoint inhibition. Highlighting potential utility in adoptive cell therapy systems, enhanced tumor growth control is observed following the addition of RORgamma agonists to T cell expansion cocktails.
Recent research has further shown that oral delivery of RORgamma agonists exhibits single agent activity with a demonstrated increase in survival in the MC38 colon cancer model. As a result, oral RORgamma agonists as monotherapy may have the potential to inhibit tumor growth and increase long term survival.
"High potency, orally available compounds are rapidly advancing at Lycera and are showing promise as a cancer immunotherapy approach. This important research provides significant additional confirmation of their potential benefits in both mono and combination therapy," said Dr. Glick. "We look forward to continuing our efforts to advance this important research platform."
RORgamma is a nuclear receptor transcription factor that drives the activation and differentiation of immune cells including Th17 (helper T cells) and Tc17 (cytotoxic) T cells. These polyfunctional cells boost the immune response to cancer cells both by direct immune system activation as well as by decreasing immune suppression.
Selective agonists have been shown to activate multiple anti-tumor mechanisms, resulting in increased immune function, durable tumor killing activity, decreases in checkpoint pathways and decreases in regulatory immune cells.
Lycera has developed potent, oral RORgamma agonists that demonstrate anti-cancer activity in animal models. RORgamma agonists represent a potential new class of immune therapy either as individual therapy or in combination with standard of care approaches in cancer.