Evidence of Clinical Activity in Patients With Tumors Positive for Predictive Biomarkers of Notch1 Overexpression Using OncoMed's Immunohistochemistry Assay

BARCELONA, Spain and REDWOOD CITY, Calif., Nov. 19, 2014 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, presented data today from the company's ongoing Phase 1a clinical trial of anti-Notch1 (OMP-52M51) in patients with certain advanced solid tumors during an oral plenary session at the 26thEORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

The purpose of the anti-Notch1 Phase 1a clinical trial is to determine a maximum tolerated dose and to assess safety, pharmacokinetics, immunogenicity and preliminary efficacy in patients, including patients with tumors overexpressing the Notch1 target as measured by a predictive diagnostic test. Among 31 patients evaluable for safety, anti-Notch1 had a manageable safety profile. The most common adverse event was on-target diarrhea, which was treated with supportive care. A Phase 2 single-agent dose of 1.5 mg/kg every three weeks was established and will be used in an expansion cohort of the Phase 1a trial that will only enroll patients with tumors that overexpress Notch1 as measured by OncoMed's predictive biomarker assay.

"Encouraging data presented today highlight why we are enthusiastic about the anti-Notch1 clinical program. We have successfully identified a single-agent dose and schedule that shows a manageable safety profile as well as early signs of anti-tumor activity," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer. "OncoMed researchers have identified a number of tumor types where Notch1 may be contributing to tumor growth and progression. In this study, we are using a proprietary immunohistochemistry test to assess Notch1 activation status and correlating those results to the drug's activity. We are seeing early signs of anti-tumor activity in several patients, with the most impressive signals observed in patients whose tumors appear to overexpress the activated form of Notch1."


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ROADSTER pivotal results (presented by Christopher J. Kwolek, MD) In the recent CREST trial, transfemoral carotid artery stenting (CAS) showed an excess periprocedural stroke rate (4.1%) when compared to carotid endarterectomy (CEA) (2.3%), while CEA was shown to carry risks of surgical complications including cranial nerve injury (CNI) (4.8%). ROADSTER is a prospective, multicenter, investigational device exemption study designed to evaluate the safety and effectiveness of a novel hybrid carotid revascularization procedure using the ENROUTE transcarotid neuroprotection system (NPS) (Silk Road Medical, Inc.). The primary endpoint was a composite of any stroke (S), myocardial infarction (MI), or death (D) through 30 days. Symptomatic and asymptomatic patients who were at high risk for complications from CEA were eligible. Between November 2012 and July 2014, 208 patients (67 lead-in, 141 pivotal) were enrolled at 18 hospitals. FDA-approved carotid stent systems, chosen according to site preference, were delivered through the direct carotid access point under high-rate flow reversal afforded by the ENROUTE NPS. Baseline pivotal population characteristics included 26% symptomatic, 35% female, and 47% age 75 or older; 56% of patients had physiologic risk factors, and 69% had anatomic risks. In the intention to treat (ITT) population, the rates for S/D/MI, S/D, and any stroke were 3.5%, 2.8%, and 1.4%, respectively. In a per protocol (PP) analysis (n = 136), the outcomes were 2.9%, 2.2% and 0.7%, respectively. There were no strokes in patients age 75 or older, nor in symptomatic patients. Transient CNI at 30 days was 0.7% and fully resolved. The upper 95% confidence interval of the hierarchical primary endpoint event rate in ROADSTER (3.5%) was statistically significantly less than the objective performance criterion (11%; P = .0047). Notably, the any stroke rate of 1.4% (0.7%, PP) in a high surgical risk population is the lowest to date for CAS and comparable to the periprocedural standard surgical risk CEA arm of CREST (2.3%). The ENROUTE transcarotid NPS appears to be safe and effective for obtaining direct carotid access and preventing embolic events during CAS.

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REDWOOD CITY, Calif., Nov. 3, 2014 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, has been granted a new patent (U.S. Patent No. 8,858,941) in the United States for OncoMed's anti-DLL4/anti-VEGF bispecific antibody (OMP-305B83) and use of the bispecific antibody in the treatment of cancer. The new patent includes both composition-of-matter and method of treatment claims for the antibody. Related patent applications are pending in the United States, Europe, Japan, China and a number of other countries worldwide.

OncoMed's anti-DLL4/ant-VEGF bispecific antibody is one of many exciting programs in our preclinical development portfolio," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "The activity of anti-DLL4, with its robust anti-cancer stem cell and dysangiogenic properties, is expected to complement the anti-angiogenic activity of anti-VEGF to create a potent anti-tumor combination. We plan to initiate clinical trials of our novel bispecific antibody as early as late 2014 or early 2015."

OncoMed recently filed an Investigational New Drug (IND) application for its anti-DLL4/anti-VEGF bispecific antibody (OMP-305B83), a novel humanized antibody generated using OncoMed's proprietary antibody technology platform. Preclinical studies suggest that the bispecific antibody may exhibit multiple mechanisms of action: (1) by targeting DLL4 and downregulating Notch pathway signaling, the antibody is expected to have an anti-CSC effect; and (2) by targeting DLL4 and VEGF, two central regulators of tumor angiogenesis, the antibody is expected to disrupt and inhibit tumor angiogenesis. In preclinical studies, the combined inhibition of DLL4 and VEGF has resulted in significant anti-tumor activity in a variety of patient-derived xenograft models.  OncoMed's anti-DLL4/anti-VEGF bispecific antibody is part of OncoMed's collaboration with Celgene Corporation.

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