On April 29, 2015 OncoMed reported new discoveries related to the company’s anti-cancer immuno-oncology pipeline during the company’s first Research and Development (R&D) Day for analysts and investors (Press release, OncoMed, APR 29, 2015, View Source [SID:1234503219]). Schedule your 30 min Free 1stOncology Demo! "OncoMed has always been focused on developing transformative anti-cancer therapeutics, and the drug discovery efforts we apply to every program have led us to identify some truly first-in-class candidates targeting fundamental cancer stem cell and immuno-oncology pathways," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "During today’s R&D Day event, we showcased the clinical, translational medicine and research science taking place at OncoMed, unveiled emerging programs that haven’t yet been in the spotlight, and provided an in-depth understanding of the way we think about drug discovery and development across our portfolio." Know more, wherever you are: Among the highlights of OncoMed’s R&D Day were data from a series of experiments that identified a novel immune therapy mechanism for demcizumab (anti-DLL4, OMP-21M18) and demonstrated synergistic activity when anti-DLL4 is combined with an anti-PD1 checkpoint inhibitor. Anti-DLL4 modulates T-cell response by reducing the accumulation of monocytic myeloid-derived suppressor cells, a key population of immunosuppressive cells that inhibit anti-tumor immune responses that are otherwise not addressed by anti-PD1 therapy. When anti-DLL4 is combined with anti-PD1, researchers observed increased inhibition of tumor growth and more robust anti-tumor immune responses in immunocompetent xenograft models as compared to either agent alone. Further, the combination of anti-DLL4 and anti-PD1 reduced tumor growth in re-implantation experiments. These results indicate that dual targeting of DLL4 and PD1 may promote effective and durable cancer therapy by increasing anti-tumor immune response and long-term immunological memory. This research could provide the foundation for a novel clinical development strategy. These data were recently presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
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A new approach, discovered by OncoMed researchers, to inhibit a known immune-oncology receptor was also disclosed publicly for the first time. GITR, a member of the tumor necrosis factor family, is known to be an important receptor in T-cell activation and regulation. OncoMed scientists have devised a novel strategy for the creation of robust T cell activating agents that utilizes fully human single-gene GITRL trimeric ligand attached to an antibody framework. The unique design of OncoMed’s proprietary strategy also enables the creation of novel bispecific agents. In preclinical studies, OncoMed’s GITRL-Fc candidate results in a potent anti-tumor immune response.
A third example of OncoMed’s immuno-oncology research efforts revealed the discovery of a novel and previously "missing" checkpoint target. Tumor cells are believed to take advantage of the immune system’s so called "checkpoints" to escape detection. While significant advances have been made in the understanding of checkpoint inhibitors, a number of orphan targets exist and these have been the subject of extensive research by OncoMed scientists for several years. One outcome of these efforts is discovery of a receptor (nicknamed "PD2"), which appears to be an activating receptor for the known checkpoint inhibitor PD-L2. Initial research by OncoMed demonstrates that "PD2" mediates important immunological functions associated with PD-L2. Activation of PD-L2 may provide an entirely new pathway by which to engage the body’s own immune system in combatting tumor cells.
In addition, OncoMed’s 2015 R&D Day included presentations of recently updated clinical data for demcizumab and tarextumab (anti-Notch2/3, OM59R5) that represent the foundation for the company’s four ongoing randomized Phase 2 clinical trials. Additionally, clinical and preclinical proof-of-concept data were presented for two of the company’s biomarker assays in development, and overview of OncoMed’s approach to elucidating cancer biology to identify and validate new leads and inform clinical trial design.
OncoMed’s 2015 R&D Day also featured special guest speakers. Manuel Hidalgo, MD, PhD, Vice Director of Translational Research, Spanish National Cancer Research Centre (CNIO), shared his experience as an investigator in the company’s demcizumab clinical trials in pancreatic cancer. Jorge DiMartino, MD, PhD, Vice President, Translational Development of Celgene Corporation provided a presentation on Celgene’s multi-product collaboration with OncoMed and the research that initially piqued Celgene’s interest.
A webcast of the R&D Day presentations can be accessed under the Investor Relations section of the company’s website (www.oncomed.com). A replay of the webcast will be archived on the OncoMed website for approximately 60 days following the presentation.