Stemming the tide

Why OncoMed’s failure might not be death knell for cancer stem cells

OncoMed’s bad April has all the hallmarks of a death knell for the once-promising technology of cancer stem cells, adding to the pile of preclinical breakthroughs that didn’t translate to the clinic. But many insiders aren’t giving up on the class, arguing the first wave of companies jumped in too early, and that better defining the biology can still lead to successful new candidates.

On April 10, OncoMed Pharmaceuticals Inc. announced its lead cancer stem cell candidate, the anti-DLL4 mAb demcizumab (OMP-21M18), missed its primary endpoint in a Phase II trial in metastatic pancreatic cancer.

A week later, the company announced its anti-Notch 2/3 antibody tarextumab (OMP-59R5) missed the Phase II primary endpoint in a small cell lung cancer (SCLC) trial, and that it was discontinuing enrollment of the anti-Notch 1 mAb bronticuzumab (OMP-52M51) in a Phase Ib trial due to GI toxicity.

And last Monday, OncoMed announced demcizumab also missed the primary endpoint in a Phase II study in non-small cell lung cancer (NSCLC), and said it put on hold two other cancer stem cell programs -- its anti-FZD7 mAb vantictumab and its anti-FZD8-Fc ipafricept -- after Bayer AG decided not to exercise its option to license the inhibitors. The company is discontinuing dosing of demcizumab in all ongoing trials.

The results cap a decade’s worth of disappointments for cancer stem cells that include conflicting preclinical data and the dissolution of several start-ups formed to develop cancer stem cell-targeted therapeutics. However, there are still at least 13 companies with cancer stem cell compounds in development, and two new companies in the space were formed last year, Metabostem S.L. and Oncternal Therapeutics Inc. (see "Cancer Stem Cell Programs").

Table: Cancer stem cell programs

Interest in cancer stem cells has declined in recent years and last month’s clinical failures at OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) have the industry questioning whether the theory still holds any clinical promise, but plenty of companies are still developing cancer stem cell-targeted therapeutics. The table includes select companies that disclosed cancer stem cell programs. At least nine still have active cancer stem cell programs, including two

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