Anticancer stem cell therapeutics

BASEL, Switzerland—Lonza, a prominent manufacturer ofbiologics, and OncoMed Pharmaceuticals Inc., a clinical-stage biopharmaceuticalcompany dedicated to improving cancer treatment, have inked an agreement forthe development and manufacture of OncoMed's pipeline of anticancer stem celltherapeutics.

Under the agreement, Lonza will produce material at itsmammalian manufacturing facility in Slough, United Kingdom. The multiproductlicense provides OncoMed with access to Lonza's GS Gene Expression System andVersion 8 manufacturing platform.

Lonza'sproprietary GS Gene Expression System uses a robust viral promoter andselection via glutamine metabolism to provide rapid development ofhigh-yielding and stable mammalian cell lines. Lonza claims that the system isused by more than 100 global pharmaceutical and biotechnology companies and is"familiar to all authorities."

Ten products havebeen approved that use the GS System, including Zenapax (Roche), Synagis(Medimmune) and Solaris (Alexion). Lonza has itself created hundreds of celllines using the GS System, many of which have been grown at large-scale andproduced product for use in clinical trials and in-market supply.

Other GS Systemusers have accumulated experience with a diverse range of products where highyields have been achieved, the company says. Many investigators use the GSSystem, not only to develop a manufacturing process, but as a tool to createrecombinant proteins for biological studies.

"We are pleased to continue to deepen our relationship withLonza," says Michael Mulkerrin, vice president of process development atOncoMed. "Over the years, Lonza's expertise has been invaluable in helping usrapidly advance our growing anticancer stem cell pipeline."

OncoMed's pipeline is focused on the development of novelmonoclonal antibodies that target cancer stem cells (CSCs), which are thesubpopulation of cells in a tumor responsible for driving growth and metastasisof the tumor. CSCs, also known as tumor-initiating cells, exhibit certainproperties which include the capacity to divide and give rise to new CSCs, aswell as the capacity to differentiate or change into the other cells that formthe bulk of the tumor. Common cancer drugs target bulk tumor cells but havelimited impact on CSCs, thereby providing a path for recurrence of the tumor.

OncoMed's product candidates target CSCs by blockingself-renewal and driving differentiation of CSCs toward a non-tumorigenicstate, and also impact bulk tumor cells. OncoMed believes that its productcandidates are distinct from the current generations of chemotherapies andtargeted therapies, and have the potential to significantly impact cancertreatment and the clinical outcome of patients with cancer.

Privately held OncoMed has advanced five anticancertherapeutics into clinical development—anti-DLL4 (demcizumab, OMP-21M18),anti-Notch2/3 (OMP 59R5), anti-Fzd7 (OMP-18R5), anti-Notch1 (OMP-52M51) andFzd8-Fc (OMP-54F28)—which target key cancer stem cell signaling pathways Notchand Wnt. In addition, OncoMed's pipeline includes several novel preclinicalproduct candidates targeting multiple validated cancer stem cell pathways,including the RSPO-LGR pathway. OncoMed has formed additional strategicalliances with Bayer Pharma AG and GlaxoSmithKline PLC.

The process development and manufacturing collaboration withLonza includes, but is not limited to, the first four of the therapeutics namedabove, plus anti-DLL4/VEGF bi-specific, which is currently in preclinicaltesting.

"OncoMed's pipeline is a great example of how emergingbiotech companies are successfully innovating in the oncology field," says Dr.Stephan Kutzer, chief operating officer of Lonza Custom Manufacturing. "Thismultiproduct contract and GS license agreement demonstrate Lonza's ability tooffer world-class expression platforms in combination with secure manufacturingcapabilities for the complete product lifecycle."