PHILADELPHIA, PA and REDWOOD CITY, CA, USA I April 21, 2015 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today announced data from seven poster presentations at the American Association of Cancer Research (AACR) Annual Meeting.
“We are pleased to have presented seven posters highlighting our ongoing discovery and development capabilities,” said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. “Leveraging our proprietary human tumor bank, human xenograft models and murine models, we have tested new combinations of our antibodies with standard-of-care chemotherapy and immunotherapy, as well as maximized optimal dosing regimens for these therapies. Our biomarker programs focus on patient selection for our clinical trials, and OncoMed continues to pursue breakthrough anti-cancer stem cell and immuno-oncology discoveries with multiple new targets and pathways.”
“Encompassing many of our clinical- and preclinical-stage candidates, the posters at AACR showcased new data related to programs targeting the Notch, Wnt, and RSPO pathways, in addition to a previously undisclosed pathway that we have been working on known as Hippo,” said John Lewicki, PhD, Executive Vice President, Chief Scientific Officer. “Highlights of OncoMed’s presentations included new preclinical observations related to the synergistic activity of anti-DLL4 with anti-PD1 inhibitors and the elucidation of anti-DLL4 immune-modulatory mechanisms of action, as well as the demonstration of enhanced activity in xenograft models when anti-cancer stem cell Wnt pathway antagonists are administered in advance of standard-of-care chemotherapy, indicating that these drugs are working to differentiate the cancer stem cell and render it more sensitive to chemotherapy. We also presented OncoMed data related to some of the important predictive biomarker work that is being applied to our clinical-stage candidates.”
Poster Presentations
Notch Pathway Programs:
Demcizumab (anti-DLL4), Tarextumab (anti-Notch 2/3), Brontictuzumab (anti-Notch1)
On Sunday, during the Immune Checkpoints Session, Minu Srivastava, Ph.D., Senior Scientist, presented preclinical research on the combination of anti-DLL4 and anti-PD1. Data from a series of experiments identified novel activities of anti-DLL4. Increased inhibition of tumor growth and anti-tumor immune response were observed when anti-DLL4 was combined with anti-PD1 as compared to anti-PD1 alone. In addition to the synergistic anti-cancer immune responses observed, 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 be an effective and durable cancer therapy by increasing anti-tumor immune response and promoting long-term immunological memory. These data were the subject of a poster titled: “Dual Targeting of Delta-like ligand 4 (DLL4) and Programmed Death 1 (PD1) inhibits tumor growth and generates enhanced long-term immunological memory” (Abstract Number: 255).
“Tarextumab (Anti-NOTCH2/3) reverses NOTCH2 and NOTCH3-dependent tumorigenicity and metastases in small cell lung cancer” (Abstract number: 2323) was presented on Monday, April 20, by Jalpa Shah, Associate Scientist, of OncoMed. Notch2 and Notch3 are expressed on tumorigenic small cell lung cancer cells and tarextumab treatment reduced cancer stem cell frequency and the incidence of metastatic growth in a panel of patient-derived small cell lung cancer tumors. Small cell lung cancer is characterized by both its frequent recurrence after responsiveness to initial therapy and high frequency of early metastases. These data support OncoMed’s ongoing randomized Phase 2 clinical trial of tarextumab in small cell lung cancer.
On Monday, Ann Kapoun, Ph.D., OncoMed’s Vice President, Translational Medicine presented “Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human Phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1)” (Abstract number: 1549). This poster describes OncoMed’s CLIA-validated immunohistochemistry (IHC) assay capable of identifying patients with Notch1 activation. OncoMed’s CLIA-validated IHC assay is currently in use for patient selection in the ongoing Phase 1a clinical trial of brontictuzumab (anti-Notch1).
Wnt Pathway Programs: Vantictumab (anti-Fzd7) and Ipafricept (Fzd8-Fc)
Based on prior observations that the anti-tumor effect of OncoMed’s Wnt antagonists is most evident in combination with chemotherapeutic agents, researchers undertook a series of experiments to ascertain the impact of various dosing regimens in preclinical models. Striking synergy was observed when the Wnt antagonists were administered prior to taxane treatment resulting in a blockade of cell cycle progression in tumor cells. These results were presented by OncoMed Senior Scientist II Wan-Ching Yen, Ph.D., on Monday, in a poster titled “Enhanced antitumor efficacy by sequential application of Wnt pathway antagonists in combination with taxanes” (Abstract Number: 2576).
Today, Marcus Fischer, Associate Scientist, presented recent results identifying pharmacodynamic and predictive biomarkers associated with the activity of ipafricept in ovarian cancer in a poster titled, “Wnt pathway antagonist ipafricept (FZD8-Fc, OMP-54F28) inhibits tumor growth and reduces tumor-initiating cell frequency in ovarian patient-derived xenograft models” (Abstract number: 4233).
Emerging Programs: Hippo and anti-RSPO3
Elsa Quintana, Ph.D., OncoMed Senior Scientist, presented new findings on the mechanisms of Hippo signaling and linking the Hippo and BMP pathways in the regulation of cancer stem cell function. “The Hippo signaling pathway mediates BMP inhibition of cancer stem cells” (Abstract number: 2322). Both BMP and HIPPO pathway signaling have been linked to fundamental stem cell functions and to cancers. The objective of this work was to study the effect of modulating BMP and Hippo signaling on tumor growth and investigate the mechanism of their anti-tumor activities.
“Discovery and evaluation of pharmacodynamic and predictive biomarkers for anti-RSPO3, a treatment that reduces tumor growth and cancer stem cell frequency in patient derived xenograft tumor models” (Abstract number: 4367) was presented today by Fiore Cattaruzza, Ph.D., Senior Scientist. These data on OncoMed’s newest clinical-stage anti-cancer stem cell therapeutic (anti-RSPO3, OMP-131R10) demonstrated activity in preclinical models for a variety of major tumor types including colon, lung, and ovarian cancers.
About Cancer Stem Cells
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed’s product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has six anti-cancer product candidates in clinical development, the most advanced of which are in randomized Phase 2 clinical trials. 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), and ipafricept (FZD8-Fc, OMP-54F28) each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed recently filed an Investigational New Drug application for anti-RSPO3 (OMP-131R10), an antibody targeting a third key cancer stem cell signaling pathway called R-spondin-LGR. OncoMed is also pursuing discovery of additional novel anti-CSC and cancer immuno-oncology product candidates. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 131
PHILADELPHIA, PA and REDWOOD CITY, CA, USA I April 21, 2015 I OncoMed Pharmaceuticals, Inc. (OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today announced data from seven poster presentations at the American Association of Cancer Research (AACR) Annual Meeting.
“We are pleased to have presented seven posters highlighting our ongoing discovery and development capabilities,” said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. “Leveraging our proprietary human tumor bank, human xenograft models and murine models, we have tested new combinations of our antibodies with standard-of-care chemotherapy and immunotherapy, as well as maximized optimal dosing regimens for these therapies. Our biomarker programs focus on patient selection for our clinical trials, and OncoMed continues to pursue breakthrough anti-cancer stem cell and immuno-oncology discoveries with multiple new targets and pathways.”
“Encompassing many of our clinical- and preclinical-stage candidates, the posters at AACR showcased new data related to programs targeting the Notch, Wnt, and RSPO pathways, in addition to a previously undisclosed pathway that we have been working on known as Hippo,” said John Lewicki, PhD, Executive Vice President, Chief Scientific Officer. “Highlights of OncoMed’s presentations included new preclinical observations related to the synergistic activity of anti-DLL4 with anti-PD1 inhibitors and the elucidation of anti-DLL4 immune-modulatory mechanisms of action, as well as the demonstration of enhanced activity in xenograft models when anti-cancer stem cell Wnt pathway antagonists are administered in advance of standard-of-care chemotherapy, indicating that these drugs are working to differentiate the cancer stem cell and render it more sensitive to chemotherapy. We also presented OncoMed data related to some of the important predictive biomarker work that is being applied to our clinical-stage candidates.”
Poster Presentations
Notch Pathway Programs:
Demcizumab (anti-DLL4), Tarextumab (anti-Notch 2/3), Brontictuzumab (anti-Notch1)
On Sunday, during the Immune Checkpoints Session, Minu Srivastava, Ph.D., Senior Scientist, presented preclinical research on the combination of anti-DLL4 and anti-PD1. Data from a series of experiments identified novel activities of anti-DLL4. Increased inhibition of tumor growth and anti-tumor immune response were observed when anti-DLL4 was combined with anti-PD1 as compared to anti-PD1 alone. In addition to the synergistic anti-cancer immune responses observed, 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 be an effective and durable cancer therapy by increasing anti-tumor immune response and promoting long-term immunological memory. These data were the subject of a poster titled: “Dual Targeting of Delta-like ligand 4 (DLL4) and Programmed Death 1 (PD1) inhibits tumor growth and generates enhanced long-term immunological memory” (Abstract Number: 255).
“Tarextumab (Anti-NOTCH2/3) reverses NOTCH2 and NOTCH3-dependent tumorigenicity and metastases in small cell lung cancer” (Abstract number: 2323) was presented on Monday, April 20, by Jalpa Shah, Associate Scientist, of OncoMed. Notch2 and Notch3 are expressed on tumorigenic small cell lung cancer cells and tarextumab treatment reduced cancer stem cell frequency and the incidence of metastatic growth in a panel of patient-derived small cell lung cancer tumors. Small cell lung cancer is characterized by both its frequent recurrence after responsiveness to initial therapy and high frequency of early metastases. These data support OncoMed’s ongoing randomized Phase 2 clinical trial of tarextumab in small cell lung cancer.
On Monday, Ann Kapoun, Ph.D., OncoMed’s Vice President, Translational Medicine presented “Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human Phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1)” (Abstract number: 1549). This poster describes OncoMed’s CLIA-validated immunohistochemistry (IHC) assay capable of identifying patients with Notch1 activation. OncoMed’s CLIA-validated IHC assay is currently in use for patient selection in the ongoing Phase 1a clinical trial of brontictuzumab (anti-Notch1).
Wnt Pathway Programs: Vantictumab (anti-Fzd7) and Ipafricept (Fzd8-Fc)
Based on prior observations that the anti-tumor effect of OncoMed’s Wnt antagonists is most evident in combination with chemotherapeutic agents, researchers undertook a series of experiments to ascertain the impact of various dosing regimens in preclinical models. Striking synergy was observed when the Wnt antagonists were administered prior to taxane treatment resulting in a blockade of cell cycle progression in tumor cells. These results were presented by OncoMed Senior Scientist II Wan-Ching Yen, Ph.D., on Monday, in a poster titled “Enhanced antitumor efficacy by sequential application of Wnt pathway antagonists in combination with taxanes” (Abstract Number: 2576).
Today, Marcus Fischer, Associate Scientist, presented recent results identifying pharmacodynamic and predictive biomarkers associated with the activity of ipafricept in ovarian cancer in a poster titled, “Wnt pathway antagonist ipafricept (FZD8-Fc, OMP-54F28) inhibits tumor growth and reduces tumor-initiating cell frequency in ovarian patient-derived xenograft models” (Abstract number: 4233).
Emerging Programs: Hippo and anti-RSPO3
Elsa Quintana, Ph.D., OncoMed Senior Scientist, presented new findings on the mechanisms of Hippo signaling and linking the Hippo and BMP pathways in the regulation of cancer stem cell function. “The Hippo signaling pathway mediates BMP inhibition of cancer stem cells” (Abstract number: 2322). Both BMP and HIPPO pathway signaling have been linked to fundamental stem cell functions and to cancers. The objective of this work was to study the effect of modulating BMP and Hippo signaling on tumor growth and investigate the mechanism of their anti-tumor activities.
“Discovery and evaluation of pharmacodynamic and predictive biomarkers for anti-RSPO3, a treatment that reduces tumor growth and cancer stem cell frequency in patient derived xenograft tumor models” (Abstract number: 4367) was presented today by Fiore Cattaruzza, Ph.D., Senior Scientist. These data on OncoMed’s newest clinical-stage anti-cancer stem cell therapeutic (anti-RSPO3, OMP-131R10) demonstrated activity in preclinical models for a variety of major tumor types including colon, lung, and ovarian cancers.
About Cancer Stem Cells
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed’s product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has six anti-cancer product candidates in clinical development, the most advanced of which are in randomized Phase 2 clinical trials. 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), and ipafricept (FZD8-Fc, OMP-54F28) each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed recently filed an Investigational New Drug application for anti-RSPO3 (OMP-131R10), an antibody targeting a third key cancer stem cell signaling pathway called R-spondin-LGR. OncoMed is also pursuing discovery of additional novel anti-CSC and cancer immuno-oncology product candidates. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company’s website: www.oncomed.com.
SOURCE: OncoMed Pharmaceuticals
Post Views: 131
