On April 17, 2016 Jounce Therapeutics, Inc., a company focused on the discovery and development of novel cancer immunotherapies coupled to patient enrichment strategies,reported that they have presented new preclinical data from two programs in the company’s immuno-oncology pipeline at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans (Press release, Jounce Therapeutics, APR 17, 2016, View Source [SID:1234511009]). The data presented represent the broad applicability of Jounce’s Translational Science Platform.
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ICOS Program
Jounce’s first presentation highlighted JTX-2011, a humanized ICOS (inducible costimulator molecule) agonist antibody being developed for the treatment of solid tumors. JTX-2011 has a dual mechanism of action, stimulating T effector cells and selectively reducing intra-tumoral T regulatory cells, thereby shifting the balance of T cells in a tumor toward anti-tumor activity. JTX-2011 has demonstrated durable anti-tumor efficacy in multiple preclinical tumor models as both a single agent and in combination with anti-PD-1 therapy. Today’s presentation provides preclinical data on JTX-2011, including evaluation of JTX-2011 in non-human primates, in which the antibody was shown to be well tolerated.
Jounce plans to file an investigational new drug application for JTX-2011 in mid-2016 and commence clinical trials evaluating JTX-2011 both as a monotherapy cancer immunotherapeutic and in combination with other immunotherapies for solid tumors in the second half of 2016.
Beyond T Cell Program
Beyond the JTX-2011 lead program, Jounce has utilized its Translational Science Platform to characterize the immune cell type infiltrate in human tumors in a large scale analysis. Using an immune cell type signature approach, tumors are characterized by the prevalence of a particular immune cell type, facilitating relevant target prioritization of that cell type and coordinated biomarker identification of those tumors. Jounce is applying this strategy to multiple immune cell types, including immuno-suppressive macrophages.
Today’s presentation demonstrates that TIM-3 and LILRB2, a novel protein-to-protein binding pair on human macrophages, discovered through this platform, may provide a new therapeutic opportunity to convert immune-suppressive macrophages to immuneenhancing macrophages. Jounce researchers were able to identify a specific "myeloid functional" epitope (the defined segment of the TIM-3 protein to which the antibody binds). In in vitro assays, only the antibodies directed to this epitope converted macrophages to a more immune active, anti-tumor type. While the "myeloid functional" anti-TIM-3 antibodies did not directly affect T cells, targeting TIM-3 on myeloid cells in this manner did have a secondary, stimulatory effect on the adaptive immune system.
"Our Beyond T Cell programs are based on the importance of targeting different immune cells types, outside of the T cell," said Deborah Law, D. Phil., chief scientific officer, Jounce. "It is our belief that this approach will allow us to pursue tumor types not currently served by therapies that target adaptive immune cells by potentially converting the tumor microenvironment from an immune-suppressive state to an immune activating, anti-tumor state. We are tremendously excited to present the first data from this program today as we work to develop myeloid-functional TIM-3 antibodies to expand the potential immunotherapeutic approaches beyond T cells. We think this approach has the potential to bring the benefits of immunotherapy to patients that are not responsive to current immunotherapies."
About the Jounce Translational Science Platform Jounce is working to develop therapies that enable the immune system to attack tumors, thereby bringing long-lasting benefits to patients. Jounce has developed its Translational Science Platform to use an unbiased bioinformatics-based approach to interrogate particular cell types within the human tumor microenvironment (the cellular environment that makes up a tumor). This platform is designed to prioritize targets and identify related biomarkers to match the right therapy to the right patients.