News Releases

Apr 18, 2018
OncoMed Presents Multiple Preclinical Abstracts Related to Immuno-Oncology Programs at the 2018 American Association for Cancer Research Annual Meeting

REDWOOD CITY, Calif., April 18, 2018 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, presented preclinical data during the American Association for Cancer Research (AACR) Annual Meeting related to two of its therapeutic candidates, anti-TIGIT (OMP-313M32), currently in the Phase 1a portion of a Phase 1a/b study, and GITRL-Fc trimer (OMP-336B11), currently in a Phase 1a study. In addition, preclinical data was presented exploring the ability of OncoMed's Wnt antagonist vantictumab (anti-FZD, OMP-18R5) to potentiate immune responses to checkpoint agents.

TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an inhibitory checkpoint receptor that binds to PVR ligand, a protein broadly expressed on tumor cells and tumor-infiltrating cells, and, in doing so, blocks T-cell activation. OncoMed's presentation (Abstract 5627) showed that anti-TIGIT treatment reduced the abundance of regulatory T-cells (Tregs) within tumors in animal models, and mechanistic studies demonstrated an important contribution of effector function for anti-tumor efficacy. "These investigations highlight the potential of our anti-TIGIT antibody," said Ann Kapoun, Ph.D., OncoMed's Vice President of Translational Medicine. "These translational research efforts inform our biomarker strategies and may help us identify patients whose tumors are most likely to benefit from our therapeutic candidates."

A series of preclinical studies (Abstract 70, Abstract 2726, Abstract 3826) from OncoMed highlighted the ability of GITRL-Fc, a novel linkerless ligand trimer that binds to the co-stimulatory receptor GITR (glucocorticoid-induced TNF receptor family-related protein), to function as a robust GITR agonist by both stimulating T-cell and NK responses and reducing the abundance of Tregs in tumors. The studies also investigated the impact of aging on anti-tumor immune response, an important and often underappreciated parameter impacting the efficacy of immuno-oncology strategies.

Another preclinical study (Abstract 1733) examined the synergistic impact of OncoMed's Wnt pathway antagonist vantictumab on the ability of checkpoint agents to promote an effective anti-tumor immune response. These data add to a growing recognition of the importance of the Wnt pathway in shaping immune function.

"The data detailed in these AACR presentations exemplify the ongoing extensive efforts to deepen our understanding of the mechanisms of action of our agents" said Austin Gurney Ph.D., OncoMed's Senior Vice President of Research and Chief Scientific Officer. "With both our anti-TIGIT and GITRL-Fc programs advancing in Phase 1 studies, these research efforts will have direct impact on informing our clinical programs." 

Below are additional highlights from the OncoMed poster presentations:

Abstract 5627 - Anti-TIGIT biomarker study: Inhibition of TIGIT induces loss of Tregs from tumors and requires effector function for tumor growth inhibition

Using a surrogate anti-TIGIT antibody, potent single-agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26 WT tumors. Anti-TIGIT efficacy was shown to require effector function for tumor growth inhibition and biomarker analysis demonstrated reduction of Treg frequency and activation of T-cells and NK cells as part of the mechanism of action of anti-TIGIT. CD226, a co-receptor for TIGIT's ligands PVR and PVRL2, was significantly upregulated in T-cells, Tregs and NK cells, reflecting a feedback loop activated by the inhibition of TIGIT activity. Anti-TIGIT gene signatures in tumors and in blood were identified from multiple syngeneic models and may be potential biomarkers for measuring anti-TIGIT activity. Additionally in a human tissue study, TIGIT expression on Tregs was found to be considerably higher than on CD8+ T-cells in multiplexed IHC panels across a panel of multiple solid tumors types.

Abstract #70 - Effect of aging on the antitumor activity of GITRL-Fc

It is now appreciated that the immune system changes in response to aging. In this study, the activity of GITRL-Fc protein was compared in both young and older mice. Compared to young mice, tumors grew faster in older mice. This may be due in part to an observed greater prevalence of myeloid-derived suppressor cells (MDSC) in older mice. GITRL-Fc significantly inhibited tumor growth in both older and younger mice with efficacy more pronounced in young mice. In older mice, GITRL-Fc (mIgG2a) was still able to deplete Tregs in tumor and increase Tregs in the spleen as has been previously shown with GITRL-Fc in young mice. A GITRL-Fc protein deficient in effector function (mIgG2a (N297A)) did not deplete Tregs in the tumor but did retain anti-tumor growth activity. Collectively, these data demonstrate that Treg depletion and activation of GITR signaling contribute to the anti-tumor efficacy of GITRL-Fc in older mice.

Abstract #2726 - In vitro functional activity of OMP-336B11, a GITRL-Fc fusion protein, on primary human immune cells

In this study, functional characterization of OMP-336B11 in various human immune cell assays was presented. OMP-336B11 enhanced activated human T-cell proliferation and augmented IL-2 induced IFNγ from human NK cells. Notably, OMP-336B11 demonstrated superior activity compared to agonist anti-GITR antibodies. OMP-336B11 is designed with an IgG1 Fc domain in order to elicit NK-mediated cytotoxicity of high GITR-expressing cells (i.e., Tregs). Co-incubation of primary human NK cells (effector) and GITR expressing cells (target) resulted in an OMP-336B11 dependent dose-titratable increase in target cytotoxicity.

Abstract #3826 - GITRL-Fc biomarker and mechanism study: GITRL-Fc reduces Treg frequency in tumors and requires effector function for inhibition of tumor growth

Using a surrogate GITRL-Fc molecule, potent single agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26.WT tumors. Biomarker analysis showed that loss of Tregs, activation of T-cells and Fc-mediated effector function are key elements in the mechanism of action of the molecule. Immuno-phenotyping of tumor-associated immune cells revealed a reduction in Treg frequency in the tumor by 24 hours post-dose that was maintained at 7 and 14 days. GITRL-Fc treatment increased proliferation and activation markers on tumor-associated CD4+ and CD8+ T-cells, suggesting an increased cytotoxic environment within the tumor. GITRL-Fc gene signatures were identified in tumors and blood from multiple syngeneic models and may be used as potential biomarkers along with multiplexed IHC panels (e.g. GITR+CD4+ T-cells, GITR+CD8+ T-cells) that were developed. Additional studies comparing intratumoral (IT) vs intraperitoneal GITRL-Fc injection demonstrated both routes of administration produced similar efficacy, suggesting IT administration may be an alternative route of administration.

Abstract #1733 - Wnt antagonists synergize with immune checkpoint inhibitors to enhance anti-tumor responses

While enhanced Wnt signaling has been shown to play a major role in cancer stem cell biology, more recent studies have implicated Wnt in the development of resistance to anti-tumor immune responses. In murine tumor models, targeting Wnt signaling using the Fzd receptor monoclonal antagonist antibody vantictumab in combination with immune checkpoint inhibitors anti-CTLA-4 or anti-PD1 induces enhanced anti-tumor responses leading to decreased tumor volume and increased infiltration of activated CD8+ T-cells into the tumor microenvironment. In addition, the data showed that combined Wnt and immune checkpoint inhibition decreased Tregs and immune suppressive myeloid cell populations, enhanced cytotoxic T-cell activity and increased antigen presentation by APCs. These results suggest that co-targeting Wnt and immune checkpoint proteins may provide valuable opportunities for novel combination strategies for immunotherapeutic clinical development.

These posters are available on the Pipeline section of OncoMed's website, www.oncomed.com.

Additional information on the meeting can be found on the AACR website www.aacr.org.

About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics. OncoMed has internally discovered a broad pipeline of investigational drugs intended to address the fundamental biology driving cancer's growth, resistance, recurrence and metastasis. Anti-TIGIT (OMP-313M32), navicixizumab (anti-DLL4/VEGF bispecific, OMP-305B83), and rosmantuzumab (anti-RSPO3, OMP-131R10) are part of OncoMed's strategic alliance with Celgene Corporation. OncoMed is independently developing GITRL-Fc (OMP-336B11), as well as continuing to pursue new drug discovery research. For further information about OncoMed Pharmaceuticals, please see www.oncomed.com.

Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding OncoMed Pharmaceuticals, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, without limitation, the mechanisms of action and potential of OncoMed's anti-TIGIT and GITRL-Fc; the importance of effector function to the anti-tumor activity of anti-TIGIT and GITRL-Fc; the advancement of OncoMed's anti-TIGIT and GITRL-Fc programs in Phase 1; OncoMed's use of biomarkers to measure the activity of anti-TIGIT and GITRL-Fc in patients; the ability of OncoMed's translational research efforts to help identify patients most likely to benefit from its therapeutic candidates; the potential for IT administration of GITRL-Fc; and the benefits of co-targeting Wnt and immune checkpoint proteins. Such forward-looking statements involve substantial risks and uncertainties that could cause OncoMed's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the preclinical and clinical development process; OncoMed's ability to raise additional capital to support the development of its unpartnered programs; and OncoMed's dependence on its key executives. OncoMed undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to OncoMed's business in general, see OncoMed's Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 9, 2018 and OncoMed's other current and periodic reports filed with the SEC.

Investor Relations Contact:

Matthew Beck
Solebury Trout
mbeck@troutgroup.com
(646) 378-2933


  
      

OncoMed Pharmaceuticals, Inc. is a wholly-owned subsidiary of Mereo BioPharma Group plc.
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