REDWOOD CITY, CA, USA I April 19, 2016 I OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), presented new data related to its GITRL-Fc immuno-oncology therapeutic candidate at the American Association of Cancer Research (AACR) Meeting. OncoMed plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for its GITRL-Fc candidate in late 2016/early 2017.
In two poster presentations, OncoMed researchers highlighted the differentiating characteristics and preclinical efficacy of this therapeutic candidate. OncoMed’s GITRL-Fc is engineered using a novel single-gene linkerless GITR ligand trimer that binds to glucocorticoid-induced tumor necrosis factor receptor. GITRL-Fc appears to act by increasing effector T-cell activation and proliferation and reducing regulatory T-cell mediated immune suppression, resulting in a potent Th1 immune response. Single-agent GITRL-Fc demonstrated profound anti-tumor activity in multiple syngeneic mouse tumor models and achieved statistically significantly greater anti-tumor activity compared with GITR agonist antibody. Notably, GITRL-Fc did not induce the broad release of cytokines in the plasma and spleen observed with the GITR agonist antibody, suggesting the potential for an improved safety profile relative to agonist antibodies.
“We believe our approach to GITR activation, using the human ligand trimer that binds to the GITR receptor, will result in more effective activation and a more specific and potent immune response compared to other approaches. In a series of preclinical studies presented at the AACR Annual Meeting, OncoMed’s GITRL-Fc demonstrated superior anti-tumor activity to an agonist antibody and induced complete tumor regressions as a single agent. Further, the broad cytokine release observed with GITR agonist antibodies was not observed using the GITR ligand approach,” said Austin Gurney, PhD, co-Chief Scientific Officer and Senior Vice President, Molecular and Cellular Biology.
The activity of GITRL-Fc was also studied in comparison and in combination with anti-PDL1 and anti-PD1. GITRL-Fc combined with either anti-PDL1 or anti-PD1 resulted in a number of complete tumor regressions and single-agent GITRL-Fc demonstrated greater anti-tumor activity than single-agent anti-PDL1 or anti-PD1. The anti-tumor activity of GITRL-Fc in combination with either anti-PDL1 or anti-PD1 reduced tumor growth beyond that of any of the agents alone. Mice “cured” with GITRL-Fc or GITRL-Fc/anti-PDL1 or GITRL-Fc/and-PD1 combination treatments were protected from re-challenge with parental tumor cells, indicating the development of sustained anti-tumor immunologic memory.
These data were presented in Abstract #2214 “GITR ligand fusion protein (GITRL-Fc) induces T cell mediated anti-tumor immune response and can combine with anti-PDL1 to enhance anti-tumor immunity and long-term immune memory” and Abstract 3215 “GITRL-Fc can significantly reduce tumor growth by stimulating innate and adaptive immunity“.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer therapeutic candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin LGR. OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate (IO#2) toward clinical trials in the 2016-2017 timeframe. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).
SOURCE: OncoMed Pharmaceuticals
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REDWOOD CITY, CA, USA I April 19, 2016 I OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), presented new data related to its GITRL-Fc immuno-oncology therapeutic candidate at the American Association of Cancer Research (AACR) Meeting. OncoMed plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for its GITRL-Fc candidate in late 2016/early 2017.
In two poster presentations, OncoMed researchers highlighted the differentiating characteristics and preclinical efficacy of this therapeutic candidate. OncoMed’s GITRL-Fc is engineered using a novel single-gene linkerless GITR ligand trimer that binds to glucocorticoid-induced tumor necrosis factor receptor. GITRL-Fc appears to act by increasing effector T-cell activation and proliferation and reducing regulatory T-cell mediated immune suppression, resulting in a potent Th1 immune response. Single-agent GITRL-Fc demonstrated profound anti-tumor activity in multiple syngeneic mouse tumor models and achieved statistically significantly greater anti-tumor activity compared with GITR agonist antibody. Notably, GITRL-Fc did not induce the broad release of cytokines in the plasma and spleen observed with the GITR agonist antibody, suggesting the potential for an improved safety profile relative to agonist antibodies.
“We believe our approach to GITR activation, using the human ligand trimer that binds to the GITR receptor, will result in more effective activation and a more specific and potent immune response compared to other approaches. In a series of preclinical studies presented at the AACR Annual Meeting, OncoMed’s GITRL-Fc demonstrated superior anti-tumor activity to an agonist antibody and induced complete tumor regressions as a single agent. Further, the broad cytokine release observed with GITR agonist antibodies was not observed using the GITR ligand approach,” said Austin Gurney, PhD, co-Chief Scientific Officer and Senior Vice President, Molecular and Cellular Biology.
The activity of GITRL-Fc was also studied in comparison and in combination with anti-PDL1 and anti-PD1. GITRL-Fc combined with either anti-PDL1 or anti-PD1 resulted in a number of complete tumor regressions and single-agent GITRL-Fc demonstrated greater anti-tumor activity than single-agent anti-PDL1 or anti-PD1. The anti-tumor activity of GITRL-Fc in combination with either anti-PDL1 or anti-PD1 reduced tumor growth beyond that of any of the agents alone. Mice “cured” with GITRL-Fc or GITRL-Fc/anti-PDL1 or GITRL-Fc/and-PD1 combination treatments were protected from re-challenge with parental tumor cells, indicating the development of sustained anti-tumor immunologic memory.
These data were presented in Abstract #2214 “GITR ligand fusion protein (GITRL-Fc) induces T cell mediated anti-tumor immune response and can combine with anti-PDL1 to enhance anti-tumor immunity and long-term immune memory” and Abstract 3215 “GITRL-Fc can significantly reduce tumor growth by stimulating innate and adaptive immunity“.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer therapeutic candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin LGR. OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate (IO#2) toward clinical trials in the 2016-2017 timeframe. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).
SOURCE: OncoMed Pharmaceuticals
Post Views: 160
