REDWOOD CITY, Calif.--(BUSINESS WIRE)--

OncoMed Pharmaceuticals, Inc., a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today announced clinical progress with its Anti-Notch2/3 (OMP-59R5) product candidate, which will trigger an $8 million milestone payment from the companys strategic collaborator GlaxoSmithKline (GSK).

OncoMed has initiated a Phase 1b/2 clinical trial in its anti-Notch2/3 antibody (OMP-59R5) program. In the Phase 1b/2 PINNACLE trial (Phase 1b/2 INvestigation of anti-Notch Antibody therapy with Cisplatin and etoposide in small cell Lung carcinoma Efficacy and safety), Anti-Notch2/3 is being tested in combination with cisplatin and etoposide in first-line extensive-stage SCLC patients. Following a Phase 1b dose escalation and expansion phase, a randomized Phase 2 clinical trial will proceed in these patients to compare the efficacy of standard-of-care cisplatin and etoposide either with Anti-Notch2/3 or with placebo. The primary endpoint of the Phase 2 part of the trial will be progression-free survival (PFS) in the Anti-Notch2/3 arm compared to a placebo arm in patients who have a particular biomarker. Key secondary and exploratory endpoints include overall survival, response rate, and safety. Enrollment of patients in both the U.S. and Europe is planned.

Dr. Robert Jotte, Developmental Co-Chair for US Oncology Lung Committee and Medical Oncologist at Rocky Mountain Cancer Centers in Denver, CO and a Principal Investigator of PINNACLE, who treated the first patient on the study noted, It is exciting to bring a treatment like Anti-Notch2/3, with a novel anti-cancer stem cell mechanism, to patients with small cell lung cancer. This disease is an aggressive form of cancer where patients are in need of new treatment options. We hope PINNACLE yields important data for these patients.

The PINNACLE study represents the second proof-of-concept study for OncoMeds Anti-Notch2/3 program. In 2012, OncoMed initiated the first Ph1b/2 Anti-Notch2/3 clinical trial called ALPINE trial (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) in first-line advanced pancreatic cancer patients. Recently, the ALPINE study has been amended to test the new chemotherapy standard-of-care of gemcitabine and Abraxane with Anti-Notch2/3 therapy. The ALPINE study is currently enrolling patients.

The initiation of the Ph1b/2 PINNACLE trial represents another major strategic and financial milestone for OncoMed as we continue to advance our first-in-class clinical pipeline of anti-cancer stem cell therapeutics, said Paul Hastings, President and Chief Executive Officer of OncoMed Pharmaceuticals. We have now initiated two proof-of-concept trials for our novel Anti-Notch2/3 antibody in the high un-met medical need indications of small cell lung cancer and pancreatic cancer. Additionally, the potential companion diagnostic biomarkers in these trials may help preselect patient candidates for the studies.

About OMP-59R5

OMP-59R5 is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Initially discovered by screening a phage display library against the Notch2 receptor, the antibody binds to a conserved epitope on Notch2 and Notch3. Preclinical studies have suggested that OMP-59R5 exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, OMP-59R5 appears to have anti-CSC effects, and (2) OMP-59R5 affects pericytes, impacting stromal and tumor microenvironment. The program is currently in two Phase 1b/2 proof-of-concept trials in cancer indications: 1) the Phase1b/2 ALPINE trial (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is testing Anti-Notch2/3 with gemcitabine and Abraxane in first-line advanced pancreatic cancer patients; 2) the Phase 1b/2 PINNACLE trial (Phase 1b/2 INvestigation of anti-Notch Antibody therapy with Cisplatin and etoposide in small cell Lung carcinoma Efficacy and safety), is testing Anti-Notch2/3 in combination with cisplatin and etoposide in first-line extensive stage SCLC patients. OMP-59R5 is part of OncoMeds collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to OMP-59R5 during certain time periods through completion of the proof-of-concept Phase 2 trials.

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. OncoMeds 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.

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OncoMed Pharmaceuticals Initiates Phase 1b/2 Clinical Trial of Anti-Cancer Stem Cell Therapeutic OMP-59R5 (Anti-Notch2 ...