April 5, 2017

OncoMed Highlights New Data Presented at the American Association for Cancer Research Annual Meeting 2017

Translational Research for Tarextumab, Rosmantuzumab and GITRL-Fc Trimer to Inform Clinical Programs

WASHINGTON and REDWOOD CITY, Calif., April 05, 2017 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, highlighted data presented during the American Association for Cancer Research (AACR) Annual Meeting related to its clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) and preclinical studies of rosmantuzumab (anti-RSPO3, OMP-131R10) and GITRL-Fc trimer (OMP-OMP-336B11). 

  • Data from OncoMed's Phase 1b clinical study of tarextumab in extensive-stage small cell lung cancer show changes in circulating tumor cells (CTCs) appear to correlate with overall survival outcomes.  The utility of using CTCs will be evaluated further in OncoMed's Phase 2 PINNACLE trial of tarextumab. 
     
  • In a series of preclinical studies, the combination of anti-RSPO3, now known as rosmantuzumab, with paclitaxel chemotherapy demonstrated synergistic anti-tumor activity in tumors with RSPO3 translocations as well as in tumors with Wnt pathway mutations.  These data may be applied in future clinical trials to determine chemotherapy combinations and/or patient selection criteria. 
     
  • Another set of preclinical studies identified and characterized biomarkers in tumors and in blood following administration of OncoMed's GITRL-Fc trimer in syngeneic murine models that may be used in upcoming clinical trials to demonstrate activity.  OncoMed is preparing to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) during the first half of 2017 for its novel GITRL-Fc trimer immuno-oncology agent.

"OncoMed is pursuing extensive efforts to identify pharmacodynamic markers that deepen our understanding of the mechanisms of action of our agents, as well as predictive biomarkers that may help us identify patients whose tumors are most likely to benefit from our therapeutic candidates," said Tim Hoey, Ph.D., OncoMed's Senior Vice President of Cancer Biology and co-Chief Scientific Officer.  "The data detailed in these AACR presentations exemplify these translational research efforts and will have direct impact in informing future clinical trial design and analyses for our tarextumab, rosmantuzumab and GITRL-Fc trimer programs."

Abstract #1727 - Circulating Tumor Cells (CTCs) in patients with extensive-stage small cell lung cancer and their association with clinical outcome
OncoMed is currently conducting the Phase 2 portion of the PINNACLE Phase 1b/2 clinical study of tarextumab in combination with standard-of-care chemotherapy in patients with extensive-stage small cell lung cancer.  Researchers looked at circulating tumor cell measurements taken from patients in the Phase 1b portion of the clinical trial to assess CTCs as a predictor of response and as pharmacodynamics biomarkers.  Blood samples from 26 patients were collected at baseline and following treatment with tarextumab plus chemotherapy.  CTCs were measured and correlated with clinical outcomes, including progression-free survival (PFS), overall survival (OS), best overall response and metastatic status.  CTCs were present in 81 percent of patients (21/26).  At baseline, higher CTC counts were associated with worse survival outcomes, liver metastasis and number of metastatic sites.  Following treatment with tarextumab and platinum-based chemotherapy, CTC counts were significantly decreased, indicating potential treatment effects.  This effect was most evident in patients treated with the designated Phase 2 dose of tarextumab (15 mg/kg) and less apparent at lower doses.  Circulating tumor cell counts will be further evaluated in the Phase 2 portion of the PINNACLE trial.

Abstract #1911 -- R-SPONDIN3 antagonism sensitizes colorectal cancer to taxane treatment
OncoMed's clinical-stage candidate, rosmantuzumab, is currently being tested in a Phase 1b clinical trial as a single agent and in combination with chemotherapy.  In the preclinical studies, tumors with RSPO3 translocations and overexpression were found to be sensitive to the combination of rosmantuzumab and a taxane, including a tumor resistant to treatment with anti-RSPO3, irinotecan or the combination of the two.  In addition, ten patient-derived xenograft models of colorectal cancer containing Wnt pathway activating mutations in APC or beta catenin were treated with the combination of rosmantuzumab plus taxane-based chemotherapy.  In these Wnt pathway mutated tumors typical of the majority of colorectal cancers, stromal cells in the tumor microenvironment are the source of RSPO3 expression.  The combination of rosmantuzumab plus a taxane resulted in synergistic inhibition of tumor growth in eight of ten models.  Anti-RSPO3 plus taxane treatment significantly reduced the number of tumor initiating cells.  These data indicate that the synergistic activity of RSPO3 inhibition in combination with taxane chemotherapy may be an effective means to improve clinical outcomes in colorectal cancer patients whose tumors overexpress RSPO3 or have Wnt pathway activating mutations.

Abstract #5621 - Prevalence of GITR expression and pharmacodynamic (PD) biomarkers in syngeneic tumor models treated by a GITR agonist (GITRL-Fc)
A series of experiments was conducted to characterize the prevalence of GITR expression in human cancer tissues and to identify pharmacodynamic biomarkers that reflect the mechanism of action of GITRL-Fc.  GITR is expressed at varying levels in multiple solid tumors on both tumor cells and immune cells.  In multiple syngeneic mouse models, GITRL-Fc trimer showed potent single-agent, dose dependent anti-tumor efficacy in large established breast, colon and melanoma tumors.  Using these models, a multi-platform approach was taken to investigate GITRL-Fc pharmacodynamic biomarkers in tumors and in blood.  It was found that GITRL-Fc increased the gene expression associated with cytotoxic T cells and NK cells. GITRL-Fc also activated CD4+ effector cells, decreased Treg frequency and increased the ratio of CD8+ T cell/Treg in the tumor. The pharmacodynamic biomarker changes in immune-related gene expression and immune cell populations observed in these preclinical models define the GITRL-Fc trimer mechanism of action and will be explored in the Phase 1 clinical trial planned for later this year.

About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology 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.  Demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), navicixizumab (anti-DLL4/VEGF bispecific, OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), rosmantuzumab (anti-RSPO3, OMP-131R10) and anti-TIGIT (OMP-313M32) are part of the company's strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).  OncoMed is independently developing brontictuzumab (anti-Notch1, OMP-52M51) and GITRL-Fc (OMP-336B11), as well as continuing to pursue new drug discovery research efforts.  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 OncoMed's expectations regarding its future clinical trial design and analyses for its tarextumab, rosmantuzumab and GITRL-Fc programs; the ability of RSPO3 inhibition to improve clinical outcomes in certain colorectal cancer patients; and the ability of OncoMed to identify pharmacodynamic and predictive biomarkers for its therapeutic candidates in the future.  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 dependence on its collaboration partners, including Celgene, GSK and Bayer, for the funding of its partnered programs; OncoMed's ability to raise additional capital to support the development of its unpartnered programs; OncoMed's reliance on third parties to conduct certain preclinical studies and all of its clinical trials; OncoMed's reliance on single source third-party contract manufacturing organizations to manufacture and supply its product candidates; 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, 2017 and OncoMed's other current and periodic reports filed with the SEC.

Contact:
Michelle Corral
Senior Director, Investor Relations and Corporate Communications
OncoMed Pharmaceuticals 
michelle.corral@oncomed.com
(650) 995-8373


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