Preclinical Comparison Study Shows Improved Anti-Tumor and Immune Responses for Anti-DLL4/VEGF Bispecific plus Anti-PD1 vs. Either Alone
National Harbor, MD and REDWOOD CITY, Calif. – November 7, 2015 – OncoMed Pharmaceuticals Inc. (NASDAQ: OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, presented new preclinical data for anti-DLL4 combined with anti-VEGF and anti-PD1 during the Society for Immunotherapy of Cancer (SITC) Conference.
A series of preclinical experiments compared the impact of anti-DLL4/VEGF bispecific and a triple blockade of DLL4-VEGF-PD1 on anti-tumor immune responses. The combination of anti-DLL4/VEGF and anti-PD1 was found to have more potent anti-tumor and enhanced immuno-oncology activity than either agent alone across a number of measures. The triple blockade of DLL4-VEGF-PD1 significantly inhibited tumor growth with more pronounced tumor regression. The addition of anti-DLL4/VEGF also improved anti-tumor activity of anti-PD1 alone in both PD1 responsive and non-responsive cancers in murine models.
“These data highlight the ability of the anti-DLL4/VEGF bispecific to combine with anti-PD1 and to modulate anti-tumor immune responses,” said Austin Gurney, PhD, Senior Vice President of Molecular and Cellular Biology. “In addition to increased anti-tumor efficacy, we note enhanced generation of memory T cell responses and reduced tumor-associated macrophages. These results show that co-targeting of DLL4 and VEGF with PD1 might be an effective and durable anti-cancer therapy in part by promoting anti-tumor immune responses and inhibiting pro-tumor immune responses.”
DLL4 is a ligand within the Notch pathway and plays important roles in regulating cancer stem cells, tumor angiogenesis and pro-tumor immune responses. OncoMed has two clinical agents targeting DLL4: demcizumab (anti-DLL4, OMP-21M18), currently in Phase 2 trials for the treatment of pancreatic cancer and non-small cell lung cancer (NSCLC), and anti-DLL4/VEGF bispecific, (OMP-305B83) currently in a Phase 1a trial in advanced solid tumors. The combination of anti-DLL4/VEGF bispecific with anti-PD1 demonstrated a distinct mechanistic profile versus prior observations of the synergistic combination of anti-DLL4 and anti-PD1 presented at the American Association for Cancer Research 2015 Annual Meeting, suggesting potential for increased T-cell activation, maintenance and memory T-cell function.
Angie Park, Ph.D., Director of Immunotherapy and Stem Cell Biology of OncoMed presented these data in a poster titled “Co-Targeting of Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF) with Programmed Death 1 (PD1) blockade inhibits tumor growth and facilitates anti-tumor immune responses.” during the Optimizing Combination Immunotherapy session.
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 product 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 has formed strategic alliances with Celgene Corporation, Bayer Pharma
AG and GlaxoSmithKline (GSK). A wholly owned immuno-oncology candidate, GITRL-Fc, and an undisclosed target that is part of OncoMed’s collaboration with Celgene are being advanced toward clinical trials in the 2016-2017 timeframe. Please see the company’s website at www.oncomed.com for additional information.
Patients interested in learning more about participating in one of OncoMed’s many clinical trials may learn more by calling 1-866-914-7347 or emailing oncomed@emergingmed.com.
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