Bayer has opted not to license from OncoMed Pharmaceuticals two first-in-class Wnt pathway inhibitor biologics designed to fight cancer, ending part of a collaboration launched in 2010, OncoMed said today.

The two Wnt pathway inhibitors are vantictumab (anti-Fzd, OMP-18R5) and ipafricept (Fzd8-Fc, OMP-54F28). Bayer cited undisclosed “strategic reasons” for not exercising its option to license the two biologic candidates, according to OncoMed.

As of June, OncoMed said, it will retain worldwide development and commercialization rights to vantictumab, ipafricept, and all other Wnt pathway biologics under the Bayer collaboration. However, the companies will continue to partner on development of small-molecule Wnt pathway inhibitors.

“While we had looked forward to collaborating with the Bayer team on the late-stage development of these biotherapeutics, we are very pleased to have worldwide rights to two promising Phase II-ready assets,” OncoMed chairman and CEO Paul J. Hastings said in a statement. “We will be conducting an internal portfolio review and prioritization as we determine next steps for all our programs, including vantictumab and ipafricept.”

OncoMed added that it has received $90 million in up-front and milestone payments that have fully funded the development of vantictumab and ipafricept. The companies launched their Wnt pathway collaboration in 2010, when OncoMed received $40 million upfront from Bayer, whose drug development business was then called Bayer Schering Pharma.

In Phase Ia and Phase Ib clinical trials, vantictumab and ipafricept have each demonstrated safety and tolerability alone and in combination with standard-of-care chemotherapies in several solid tumors. OncoMed is completing two Phase Ib combination clinical trials of vantictumab—one in HER2-negative breast cancer with paclitaxel and the other in advanced pancreatic cancer with gemcitabine and Celgene’s Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound)

OncoMed is also completing two Phase Ib combination clinical trials of ipafricept—one in ovarian cancer together with carboplatin and paclitaxel and the other in pancreatic cancer with gemcitabine and Abraxane.

During last year’s American Society of Clinical Oncology (ASCO) Annual Meeting and the European Society for Medical Oncology (ESMO) 2016 Congress, OncoMed presented interim data for each trial showing early indications of antitumor activity.

The company has also cited preclinical studies showing evidence of synergies when the Wnt inhibitor compounds are administered sequentially following the use of taxane-based chemotherapies.  Published preclinical studies also point to the Wnt pathway as being a possible potentiator of immune response in tumors.

Demcizumab Fails Phase II Trial

The partial end of the Bayer collaboration was one of two negative events disclosed today by OncoMed.

Separately, the company disclosed that it is halting the Phase II YOSEMITE trial assessing demcizumab (anti-DLL4, OMP-21M18) as part of a combination cancer therapy, after the candidate missed its primary endpoint of progression-free survival (PFS). Demcizumab is among candidates being co-developed by OncoMed under an up-to-$3.3 billion-plus partnership with Celgene launched in 2013.

YOSEMITE assessed demcizumab in combination with Abraxane plus gemcitabine in previously untreated patients with metastatic pancreatic cancer.

For patients receiving demcizumab in combination with Abraxane plus gemcitabine, the overall median PFS was 5.5 months, which was identical to the Abraxane, gemcitabine plus placebo group.  No significant differences were observed when the individual treatment arms were compared to the Abraxane, gemcitabine plus placebo arm. Median PFS was 5.4 months in patients receiving a single truncated course of demcizumab and 5.5 months in patients receiving two truncated courses.

Worse, an interim median analysis for the study’s secondary endpoint of overall survival did not show a benefit for demcizumab in combination with Abraxane plus gemcitabine compared to the study’s Abraxane-gemcitabine-plus-placebo arm.

Demcizumab is a humanized monoclonal antibody targeting delta-like ligand 4 (DLL4), a key member of the Notch signaling pathway.  Based on preclinical studies, OncoMed said, demcizumab may have a multipronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor, and augmenting antitumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

Investors responded to the YOSEMITE trial failure with a stock sell-off that saw OncoMed’s share price plunge 43% from Friday’s close of $8.76 to $5.00 in premarket trading as of 9:03 a.m.

YOSEMITE is one of two Phase II trials designed to assess demcizumab. The second study, DENALI, is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small-cell lung cancer patients.

Demcizumab is also the subject of a Phase Ib trial combining the candidate with Merck & Co.’s anti-programmed cell death protein 1 (anti-PD1) antibody Keytruda® (pembrolizumab) in solid tumor patients, a study launched last year.

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