OncoMed Pharmaceuticals, Inc.  
 
 
 

Development status of OncoMed's anti-CSC programs

Overview

OncoMed is advancing five 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 stem cells and proprietary platform discovery technologies.  

For each cancer stem cell pathway, there exist multiple potential therapeutic opportunities. Three of our clinical-stage novel product candidates target the key Notch cancer stem cell pathway and two product candidates target the key Wnt cancer stem cell pathway. OncoMed’s product candidates are in clinical development in a variety of cancer indications.  Predictive biomarkers are being tested in a number of our clinical studies to identify the patients most likely to derive greater benefit from a given OncoMed product candidate.

 

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 optimized to block the key Notch signaling pathway in cancer stem cells. Specifically, demcizumab selectively targets Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway—a pathway known to be important in cancer stem cells and cancer.

Blocking DLL4 has been shown in preclinical studies to result in broad-spectrum anti-tumor activity via multiple mechanisms, including disrupting angiogenesis, inhibiting cancer stem cell growth, and promoting cell differentiation, and potentially immune activation. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.
Public presentations of the demcizumab clinical studies include:

 

 

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

OncoMed has a preclinical antibody program that 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 and anti-angiogenic activity and potentially immune modulatory effects.  An Investigational New Drug (IND) application filing with the US Food and Drug Administration (FDA) to enable first-in-human clinical studies is planned for as early as 2014.  
This program is part of OncoMed’s collaboration with Celgene Corporation.

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

Tarextumab (anti-Notch2/3, OMP-59R5) is a novel anti-cancer stem cell antibody identified by screening against the Notch3 receptor that binds to and prevents signaling through both the Notch2 and Notch3 receptors.  Tarextumab has been shown in preclinical models to have broad-spectrum anti-tumor activity via inhibition of cancer stem cell growth, and promoting cell differentiation, as well as disrupting tumor angiogenesis by inhibiting vascular pericytes.

OncoMed has completed a single-agent Phase 1 clinical trial testing tarextumab in advanced solid tumor patients in 2013.  Tarextumab is well tolerated as a single agent, and evidence of Notch pathway modulation and potential early single-agent activity manifested by prolonged stable disease has been observed.  Two Phase 1b/2 clinical studies of Tarextumab in combination with standard-of-care anti-cancer agents in patients with advanced pancreatic cancer and extensive-stage small cell lung cancer are ongoing. Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK).
Public presentations of the OMP-59R5 clinical studies include:

 

Anti-Notch1 (OMP-52M51)

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 have broad-spectrum anti-tumor activity by inhibiting of cancer stem cell growth, and promoting cell differentiation, as well as disrupting tumor angiogenesis. Anti-Notch1 is being studied as a single agent in two ongoing Phase 1a clinical trials among patients with advanced solid tumors or hematologic malignancies. Anti-Notch1 is part of OncoMed’s collaboration with GSK.
Public presentations of data from the Anti-Notch1 clinical studies:

Vantictumab (anti-Fzd7, OMP-18R5)

OncoMed has completed enrollment in a Phase 1a clinical study of vantictumab in advanced solid tumor patients. Vantictumab demonstrates evidence of Wnt pathway modulation and potential early single-agent activity manifested by prolonged stable disease has been observed. Three Phase 1b clinical trials of vantictumab in combination with standard-of-care chemotherapy in distinct solid tumor indications were initiated in 2013. The three trials include a Phase 1b trial in HER2-negative breast cancer (vantictumab + paclitaxel), a Phase 1b trial in advanced non-small cell lung cancer (vantictumab + docetaxel), and a Phase 1b trial in advanced pancreatic cancer (vantictumab + gemcitabine + Abraxane). Vantictumab is part of OncoMed’s collaboration with Bayer Pharma AG.
Public presentations of the vantictumab clinical studies include:

 

 

 

Ipafricept (FZD8-Fc, OMP-54F28)

Ipafricept (FZD8-FC, OMP-54F28) 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 selectively binds Wnt ligands that are activators of Wnt signaling. FZD8-Fc has shown potent anti-cancer stem cell effects and induces tumor cell differentiation in preclinical studies. OncoMed has reported that in its 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. Three Phase 1b clinical trials of ipafricept are ongoing: one in pancreatic cancer (gemcitabine/nab-paclitaxel + ipafricept), one in hepatocellular carcinoma (sorafenib + ipafricept), and one in ovarian cancer (carboplatin/paclitaxel + ipafricept). Ipafricept is part of OncoMed’s collaboration with Bayer.
Public presentations of data from the OMP-54F28 program:

Wnt 3rd Biologic

OncoMed is currently advancing a third Wnt pathway biologic in preclinical studies.  This program is part of OncoMed’s collaboration with Bayer.

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.

 

 

 

Anti-RSPO (OMP-131R10)

Human R-spondin (RSPO) proteins signal through the leucine-rich repeat-containing G-coupled receptors (LGRs) and the RSPO-LGR pathway is believed to be an important cancer stem cell pathway.  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 and demonstrated the anti-cancer stem cell activity of these antibodies in preclinical studies.  OncoMed plans to file an Investigational New Drug filing on its first antibody targeting the RSPO-LGR pathway, anti-RSPO3 (OMP-131R10), in early 2015.  This program is part of OncoMed’s collaboration with Celgene Corporation.

 

New Pathways

OncoMed has multiple new pathway discovery and preclinical efforts advancing in-house. These programs are emerging from the company's focused efforts in elucidating cancer stem cell and cancer biology, expertise in mAb and protein therapeutics and expertise in translational/predictive medicine.  These efforts include discoveries in an undisclosed cancer stem cell pathway with immunotherapy potential that is part of our collaboration with Celgene Corporation.