OncoMed Pharmaceuticals, Inc.  


OncoMed is advancing seven first-in-class anti-cancer stem cell product candidates in clinical trials. All of these product candidates were discovered at OncoMed using our in-depth knowledge of cancer biology and proprietary platform discovery technologies.  Four of our clinical-stage novel product candidates target the Notch cancer stem cell pathway and two product candidates target the key Wnt cancer stem cell pathway.

Our most recent product candidate to enter the clinic is targeting RSPO-LGR, a cancer stem cell pathway discovered by OncoMed scientists. For each cancer stem cell pathway, there exist multiple potential therapeutic opportunities. We utilize biomarkers throughout our clinical development efforts to enhance our understanding of how our drugs work and help identify the patients most likely to derive greater benefit from a given OncoMed product candidate. Patients interested in finding out more about OncoMed clinical trials can use our Clinical Trial Matching Service.


Demcizumab (anti-DLL4, OMP-21M18)

One of OncoMed's first anti-cancer stem cell product candidates in the clinic, demcizumab (anti-DLL4, OMP-21M18), is a monoclonal antibody that selectively targets Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway. The Notch pathway is known to be important in cancer stem cells and cancer.

Blocking DLL4 has been shown in preclinical studies to result in anti-tumor activity via multiple mechanisms, including inhibiting cancer stem cell growth and promoting cell differentiation, disrupting angiogenesis and potentially enhancing anti-tumor immune response.

In Phase 1a clinical studies, demcizumab has demonstrated initial single-agent activity, including early evidence of durable anti-tumor responses. Results from Phase 1b studies of demcizumab plus standard-of-care chemotherapy in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and pancreatic cancer demonstrate the safety of our truncated dosing approach, anti-tumor responses and promising signals of prolonged survival benefit. These results are being confirmed in ongoing randomized Phase 2 trials of demcizumab. The DENALI trial will assess the efficacy of demcizumab with carboplatin and pemetrexed in first-line non-squamous NSCLC. The YOSEMITE trial is evaluating demcizumab and gemcitabine plus Abraxane in patients with first-line metastatic pancreatic cancers. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing. To learn more about OncoMed’s ongoing clinical studies of demcizumab, please see Demcizumab clinicaltrials.gov

Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

The most recent public presentations of the demcizumab clinical studies include:


Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a novel anti-cancer stem cell antibody that prevents signaling through both the Notch2 and Notch3 receptors. Tarextumab has been shown in preclinical models to inhibit cancer stem cell growth, and promote cell differentiation, as well as disrupt tumor angiogenesis by inhibiting vascular pericytes.

Tarextumab is currently being studied in the randomized Phase 2 PINNACLE trial, testing tarextumab in combination with physician’s choice of etoposide and cisplatin or etoposide and carboplatin in first-line extensive stage small cell lung cancer patients. The Phase 1b portion of the PINNACLE clinical trial demonstrated that tarextumab is well tolerated in combination with standard of care chemotherapies. In small cell lung cancer, tarextumab has demonstrated dose-dependent and biomarker driven activity. A randomized Phase 2 clinical trial of tarextumab in combination with gemcitabine and Abraxane has been discontinued. The Phase 2 clinical trial of tarextumab in SCLC is ongoing; additional information is listed here: OMP59R5 ClinicalTrials.gov

Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK).

Public presentations of tarextumab data include:


Vantictumab (anti-Fzd7, OMP-18R5)

Vantictumab targets the Wnt cancer stem cell pathway and has demonstrated evidence of Wnt pathway modulation as well as early signals of single-agent activity (i.e. prolonged stable disease).

OncoMed is conducting two Phase 1b clinical trials of vantictumab in combination with standard-of-care chemotherapy – a Phase 1b trial in HER2-negative breast cancer (vantictumab + paclitaxel) and a Phase 1b trial in advanced pancreatic cancer (vantictumab + gemcitabine + Abraxane). Information about OncoMed’s clinical studies of vantictumab is available here: Vantictumab ClinicalTrials.gov.

Vantictumab is part of OncoMed’s collaboration with Bayer Pharma AG.

Public presentations on vantictumab clinical studies include:


Ipafricept (FZD8-Fc, OMP-54F28)

Ipafricept (FZD8-FC, OMP-54F28) selectively binds Wnt ligands that are activators of Wnt signaling. It is a fusion protein that consists of a portion of the Frizzled 8 receptor from the Wnt pathway fused to the Fc domain of a human IgG1. Ipafricept has shown potent anti-cancer stem cell effects and induces tumor cell differentiation in preclinical studies.

Two Phase 1b clinical trials of ipafricept are ongoing: one in pancreatic cancer (gemcitabine/nab-paclitaxel + ipafricept) and one in ovarian cancer (carboplatin/paclitaxel + ipafricept). In a Phase 1a clinical trial, ipafricept was well tolerated as a single agent and demonstrated evidence of Wnt pathway modulation and potential early single-agent activity manifested by prolonged stable disease. Links to the ongoing ipafricept clinical trials on clinicatrials.gov can be accessed here: OMP-54F28 ClinicalTrials.gov.

Ipafricept is part of OncoMed’s collaboration with Bayer Pharma AG.

Public presentations of ipafricept data include:


Brontictuzumab (Anti-Notch1, OMP-52M51)

Bronticuzumab (Anti-Notch1, OMP-52M51) is a novel anti-cancer stem cell antibody that binds the Notch1 receptor. Blocking Notch1 has been shown in preclinical models to inhibit cancer stem cell growth, and promote cell differentiation, as well as to disrupt tumor angiogenesis. Notch1 signaling is prevalent in several solid tumor types, including certain breast, esophageal, colorectal, gastric, pancreatic and small cell lung cancers, as well as adenoid cystic carcinoma and cholangiocarcinoma. Single-agent anti-tumor activity was observed in OncoMed’s Phase 1a study of brontictuzumab in patients with certain advanced solid tumors, particularly in biomarker-defined patients whose tumors tested positive for overexpression of the activated form of Notch1. OncoMed is currently enrolling patients with metastatic colorectal cancer in a Phase 1b clinical trial intended to assess safety, preliminary efficacy and immunogenicity, as well as predictive and pharmacodynamics biomarkers of brontictuzumab in combination with trifluridine/tipiracil (Lonsurf®). Links to the ongoing brontictuzumab clinical trials are listed here: OMP-52M51 ClinicalTrials.gov

OncoMed retains worldwide rights to develop brontictuzumab.

Public presentations of data from brontictuzumab studies include:


Anti-DLL4/VEGF bispecific (OMP-305B83)

OncoMed’s anti-DLL4/VEGF bispecific targets both DLL4 on the Notch cancer stem cell pathway and the VEGF receptor. This antibody is intended to have both anti-cancer stem cell, immunomodulatory and anti-angiogenic activity. The bispecific antibody was discovered using OncoMed’s proprietary MAbTrap™ antibody display technology, which enables the rapid identification of monoclonal antibodies that bind targets with high affinity and specificity. The antibody is also the first program based on OncoMed’s BiMAb™ bispecific platform technology, which enables bispecific antibodies with traditional antibody shape, to enter clinical testing. OncoMed is currently enrolling patients with advanced refractory solid tumors in a Phase 1a clinical trial with metastatic second-line colorectal cancer or platinum-resistant ovarian cancer in two Phase 1b clinical trials of anti-DLL4/VEGF bispecific antibody in combination with a standard chemotherapy regimen.(see ClinicalTrials.gov listing here: Bispecific ClinicalTrials.gov).

This program is part of OncoMed’s collaboration with Celgene Corporation.

Public presentations on Anti-DLL4/VEGF bispecific studies include:


Anti-RSPO3 (OMP-131R10)

The RSPO-LGR pathway is believed to be an important cancer stem cell pathway. Human R-spondin (RSPO) proteins signal through the leucine-rich repeat-containing G-coupled receptors (LGRs). Antibodies that disrupt binding of RSPO proteins to LGRs, or that disrupt RSPO activation of LGR signaling, are potential anti-cancer agents. OncoMed has identified multiple antibodies targeting the RSPO-LGR pathway. OncoMed initiated a Phase 1a/1b clinical study for its first antibody targeting the RSPO-LGR pathway, anti-RSPO3 (OMP-131R10). A proprietary biomarker to screen prospectively screen patients for expression of RSPO is being developed in conjunction with this clinical program. Anti-RSPO3 has demonstrated activity in preclinical models against a variety of major tumor types, including colon, lung and ovarian cancers. Information on OncoMed’s anti-RSPO3 clinical program is available here: Anti-RSPO3 clinical program.

This program is part of OncoMed’s collaboration with Celgene Corporation.

Public presentations on anti-RSPO3 (OMP-131R10) include:


Wnt Small Molecules

OncoMed and Bayer Pharma AG are jointly working to discover small molecules targeting the Wnt Pathway as part of the strategic collaboration announced in June 2010.


Emerging Pipeline in Immunotherapy

OncoMed has multiple new discovery and preclinical efforts advancing internally. Among the disclosed preclinical immuno-oncology compounds being advanced are an anti-TIGIT program in collaboration with Celgene. This program is advancing into Phase 1 clinical trials in the first half of 2017. OncoMed expects to file an Investigational New Drug Application for its wholly owned GITRL-FC trimer in 2017. GITRL is a member of the tumor necrosis factor (TNF) family of ligands and functions to activate the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptors) to enhance T-cell modulated immune responses. OncoMed’s GITRL-Fc agent is engineered using a novel single-gene linkerless GITRL trimer which enables effective GITR activation and robust anti-tumor immune response.