NEW YORK and ANN ARBOR, Mich., May 16, 2018 /PRNewswire/ — Lycera Corp., a privately held biopharmaceutical company developing breakthrough immune modulatory medicines, today announced the publication of new preclinical research findings describing the potential utility of the Company’s most advanced cancer immunotherapy platform, selective RORgamma agonists, in adoptive cell therapy applications. RORgamma is a nuclear receptor transcription factor that serves as a master control switch of the immune system, driving the generation and function of Type 17 effector immune cells, Th17 (helper), and Tc17 (cytotoxic) T cells. These Type 17 immune T cells play an important role in mediating anti-tumor immune responses.
A research team, led by Chrystal Paulos, Ph.D., at the Medical University of South Carolina, in collaboration with scientists from Lycera and the University of Michigan School of Medicine, report key preclinical data in a Cancer Research article titled, “In Vitro Priming of Adoptively Transferred T Cells with a RORg Agonist Confers Durable Memory and Stemness In Vivo.” Important findings from this translational research include:
- When applied during the manufacture of CAR T-cells, RORgamma agonists enhance effector functions, such as cytokine production and cytotoxic activity, against multiple tumors in vitro.
- Compared to untreated CAR T-cells, infusion of CAR T-cells produced with the addition of RORgamma agonists results in greater tumor regression and improved survival in an in vivo model of human mesothelioma, as well as in murine tumor models.
- Treatment with RORgamma agonists in vitro results in more tumor-infiltrating lymphocytes that co-secrete cytokines, display a stem memory phenotype, and have superior in vivo persistence compared to untreated cells.
- The enhanced effector function and persistence following RORgamma agonist treatment provide superior protection against tumor re-challenges for months.
“Maintaining fitness of CAR T-cells or other cell therapy products during their production and the persistence of these cells upon transfer into patients with tumors continue to be challenges in the field of adoptive cell therapy,” commented Dr. Paulos. “In this published work, we show that a short in vitro treatment with Lycera’s RORgamma agonist has long-lasting effects on T-cells, resulting in superior tumor eradication and protection from tumor regrowth. These results suggest there may be benefit to using RORgamma agonists in adoptive cell therapy protocols.”
“We are pleased to report the publication of promising research results that underscore the potential of our approach to reprogramming the immune response by targeting the RORgamma transcription factor. These results support and extend our previous work on understanding the anti-tumor mechanisms of action of RORgamma agonists, and we have entered into multiple clinical trials with our lead RORgamma agonist, LYC-55716, both as a monotherapy and in combination treatment with pembrolizumab,” said Paul Sekhri, President and CEO of Lycera. “The published data suggest that in vitro use of RORgamma agonists also has the potential to enhance the activity of adoptive cell therapy, such as with CAR T-cells. Interestingly, treatment with RORgamma agonists led to long-lasting anti-tumor memory T-cells, which may mitigate one of the key challenges of adoptive cell therapy, namely, the lack of CAR T persistence.
We are grateful to our collaborators who have played an important role in helping to elucidate these key attributes of our first-in-class approach and platform.”
The article citation is: Hu X, Majchrzak K, Liu X, Wyatt MM, Spooner CJ, Moisan J, Zou W, Carter LL, Paulos CM. In vitro priming of adoptively transferred T cells with a RORg agonist confers durable memory and stemness in vivo. Cancer Research. 2018. [Epub ahead of print]. doi: 10.1158/0008-5472.CAN-17-3973.
About RORgamma agonists
RORgamma is a nuclear receptor transcription factor that serves as a master control switch of the immune system, driving the activation and differentiation of immune cells, including Th17 (helper T-cells) and Tc17 (cytotoxic T cells) T cells. Lycera has discovered selective and potent oral agonists that target RORgamma and which are advancing to the clinic for the potential treatment of a broad range of cancers. These RORgamma agonists have demonstrated single agent therapeutic activity in multiple animal models of cancer. In addition, ex vivo treatment with Lycera’s RORgamma agonist compounds has been shown to enhance the therapeutic benefit of adoptive T-cell therapy by improving both immune cell persistence and activation.
Lycera is a biopharmaceutical company developing novel oral immune modulators for the treatment of autoimmune diseases and cancer. Based on successful progress of its world-class R&D platform, including expertise in immune metabolism, cell signaling, and immune cell differentiation, Lycera commenced multiple clinical programs in 2016. The company is advancing a wholly owned, oral, gut-directed ATPase modulator, designated LYC-30937-EC, for the treatment of autoimmune disease, and has entered Phase 2 clinical studies in patients with ulcerative colitis and psoriasis. A second product candidate, LYC-55716, an oral RORgamma agonist, is progressing in the Phase 1/2a ARGON trial, a monotherapy study in patients with advanced solid tumors, as well as in a Phase 1b combination trial with pembrolizumab for advanced non-small cell lung cancer. Lycera has an exclusive strategic collaboration with Celgene Corporation to advance Lycera’s proprietary pipeline for cancer and immune-mediated diseases.
Lycera’s leadership possesses deep experience in drug discovery, development, and commercialization and has established close relationships with renowned thought leaders and clinical researchers worldwide. Lycera was founded in 2006 based on an initial scientific platform in-licensed from the University of Michigan. Lead investors in Lycera include InterWest Partners, ARCH Venture Partners, Clarus Ventures, and EDF Ventures.
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