OncoMed Pharmaceuticals, Inc. (NASDAQ: OMED), a clinical-stage company developing novel therapeutics which target cancer stem cells (CSCs), or tumor-initiating cells, presented data in two posters highlighting the company's translational research and biomarker efforts for its tarextumab (anti-Notch2/3, OMP-59R5) and demcizumab (anti-DLL4, OMP-21M18) clinical programs. These data were presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

"The data from the Phase 1b clinical trials of tarextumab and demcizumab demonstrate that our preclinical understanding of on-target drug activity and predictive biomarkers is being validated in the clinic as we study actual patient tumor samples," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer. "In the ALPINE Phase 1b study in advanced pancreatic cancer, we see clear evidence that tarextumab modulates the Notch cancer stem cell pathway in patient samples and that there is a potential association between tumors that show higher levels of Notch3 gene expression and best responses to tarextumab treatment. In the demcizumab poster presentation, a case study is described from our Phase 1b trial in pancreatic cancer in which the tumor response to treatment that occurred in the clinic correlates with what we observe using patient-derived xenograft models. This may provide insights into the development of potential biomarkers of response to demcizumab treatment in that program."

Tarextumab -- OncoMed researchers analyzed tissue samples including serial tumor biopsies from patients with metastatic pancreatic cancer in the Phase 1b ALPINE clinical trial of tarextumab in combination with gemcitabine plus Abraxane(R) (paclitaxel protein-bound particles for injectable suspension) (albumin bound). Pharmacodynamic biomarkers showed that tarextumab at doses of 7.5mg/kg and above had marked inhibitory effects on genes associated with Notch signaling and stem cell cells in hair follicles and blood cells. Genes indicating stem cell differentiation were up-regulated at the same doses in these samples. In four paired serial tumor biopsies, Notch3 protein levels were significantly reduced by the combination of tarextumab-gemcitabine-Abraxane. Importantly, gene signatures reflective of Notch signaling, tumor metastasis, and cancer stem cells were all markedly down-regulated following treatment with tarextumab-gemcitabine-Abraxane relative to baseline tumors. These data are consistent with the proposed mechanism of action of tarextumab to inhibit Notch signaling and to reduce cancer stem cells in tumors. The dose of tarextumab in the ongoing Phase 2 portion of the ALPINE study is 15mg/kg every 2 weeks.

Using OncoMed's proprietary Notch3 gene expression assay for predictive biomarkers, OncoMed researchers observed an emerging trend suggesting that patients with higher levels of tumor-derived Notch3 gene expression at baseline exhibit improved response to tarextumab treatment. Notch3 gene expression was evaluable in pancreatic tumor samples from 80 percent of the patients enrolled in the Phase 1b trial. Notch3 gene expression is now being evaluated as a predictive biomarker for tarextumab in the Phase 2 portion of the ALPINE clinical trial.

These data were presented today by lead author Ann M. Kapoun, Ph.D., OncoMed's Vice President, Translational Medicine, in a poster titled: Biomarker analysis in Phase 1b study of anti-cancer stem cell antibody Tarextumab (TRXT) in combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) demonstrates pharmacodynamic (PD) modulation of the Notch pathway in patients (pts) with untreated metastatic pancreatic cancer (mPC) (abstract# 465).
Demcizumab -- In the demcizumab presentation, a patient tumor sample from the Phase 1b clinical trial of demcizumab combined with standard of care was evaluated using OncoMed's proprietary patient-derived xenograft models and the anti-tumor response was compared between the clinical and preclinical studies. The Phase 1b patient progressed rapidly on treatment with a combination of demcizumab and gemcitabine. When a tumor derived from the Phase 1b patient was grown in a xenograft model, the new tumor was also insensitive to gemcitabine and the combination of demcizumab plus gemcitabine. This tumor was significantly more sensitive to the triple combination using demcizumab-gemcitabine-Abraxane. These data suggest that OncoMed's patient-derived xenograft models can mirror activity in the clinic. Analysis of key characteristics of responsive tumors relative to non-responsive tumors may provide insights into potential biomarkers of sensitivity to demcizumab treatment.

Data from this study were presented during the Preclinical Models poster session on Wednesday, November 19, 2014 by Manuel Hidalgo, M.D., Ph.D., CNIO-CIOCC-START, a lead clinical investigator for the demcizumab Phase 1b study, in a poster titled: Preclinical and Clinical Activity of Anti-DLL4 (Demcizumab) in Combination with Gemcitabine Plus nab-Paclitaxel in Pancreatic Cancer (abstract #166).

"The biomarker programs associated with each of our clinical candidates directly informs and guides predictive biomarker efforts in randomized Phase 2 clinical trials and beyond," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "This approach makes for smarter, more strategic drug development that we believe will translate into improved patient care and outcomes."

 Celgene International Sàrl (NasdaqGS: CELG) 0.79%, a wholly-owned subsidiary of Celgene Corporation, today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for OTEZLA® (apremilast), the Company's oral selective inhibitor of phosphodiesterase 4 (PDE4), in two therapeutic indications: 1

For the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or, who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA).

Alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.

Psoriasis is an immune mediated skin condition characterised by raised scaly lesions on the skin. It affects approximately 14 million people across Europe2 and about 125 million people worldwide.3 Plaque psoriasis, also called psoriasis vulgaris, is the most common form of the disease, representing about 80 percent of cases.4 Up to 30 percent of people with psoriasis may develop psoriatic arthritis, which involves pain and swelling in jointsand other manifestations and may lead to significant disability.5

“This CHMP positive opinion is an important step forward for people with psoriasis and psoriatic arthritis in Europe. These immune mediated diseases are frequently debilitating and cause severe physical and emotional pain to the individual,” stated Tuomo Pätsi, President, Celgene Europe, the Middle East and Africa (EMEA). “We are proud to have moved one step closer to offering patients OTEZLA®, a new, oral treatment approach that could significantly help control their symptoms and make a considerable difference to their quality of life.”

In the ESTEEM studies, which form the basis of CHMP's positive opinion for apremilast in psoriasis, treatment resulted in significant and clinically meaningful improvements in plaque psoriasis as measured by PASI-75 (a 75 percent improvement in the Psoriasis Area Severity Index) scores at week 16, the primary endpoint.6,7 Patients on apremilast also benefited from significant improvements in difficult to treat areas, such as nail and scalp, and itch, known to have a marked impact on patients' quality of life and perception of disease severity.8,9,10

In the PALACE program, which forms the basis for CHMP's positive opinion for apremilast in psoriatic arthritis, treatment resulted in significant and clinically meaningful improvements in the signs and symptoms of psoriatic arthritis, as measured by the modified ACR-20 (a 20 percent improvement in the American College of Rheumatology disease activity criteria) response at 16 weeks, the primary endpoint. 7,11 Patients on apremilast showed improvement across multiple disease manifestations specific to psoriatic arthritis, such as swollen and tender joints, as well as dactylitis, enthesitis and overall physical function.12,13,14

In the two Phase III programs, PALACE and ESTEEM, the clinical response of OTEZLA was maintained through week 52 across multiple endpoints. 15,16

Across these phase III clinical studies, the most commonly reported adverse reactions were consistently diarrhoea, nausea, upper respiratory tract infection, tension headache and headache.6,11 These adverse reactions were mostly mild to moderate in severity. Gastrointestinal adverse reactions generally occurred within the first two weeks of treatment and usually resolved within four weeks.6,11 During the placebo-controlled phase of the clinical trials, the rate of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, was comparable between placebo and apremilast groups.6,11

OTEZLA® was approved on March 21, 2014 by the U.S. Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis and on September 23, 2014 for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In Canada, OTEZLA was approved for the treatment of moderate-to-severe plaque psoriasis in November 2014. A New Drug Submission (NDS) for psoriatic arthritis was submitted to Canadian Health Authorities in the second quarter of 2013. Marketing authorisation applications are ongoing in other countries, including Australia and Switzerland.

The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within two to three months. If approval is granted, detailed conditions for the use of this product will be described in the Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).