On April 10, 2017 OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported top-line results from the company’s Phase 2 YOSEMITE clinical trial of demcizumab (anti-DLL4, OMP-21M18) in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in previously untreated patients with metastatic pancreatic cancer (Press release, OncoMed, APR 10, 2017, View Source [SID1234518519]). The randomized Phase 2 "YOSEMITE" trial was designed to assess the efficacy and safety of demcizumab plus standard-of-care chemotherapy in first-line metastatic pancreatic cancer with the primary endpoint of progression-free survival and a secondary endpoint of overall survival. The trial did not meet the primary endpoint of progression-free survival. Additionally, the interim median overall survival analysis did not show a benefit for demcizumab in combination with Abraxane plus gemcitabine compared to the Abraxane, gemcitabine plus placebo arm in patients with first-line metastatic pancreatic cancer.

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"Patients in all three arms of the Phase 2 YOSEMITE trial surpassed the published median overall survival rates for Abraxane plus gemcitabine in first-line metastatic pancreatic patients. While the interim median overall survival was 13.2 months in the pooled demcizumab arms, the interim median overall survival of Abraxane plus gemcitabine was not reached at the time of these analyses. Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial. We will conduct additional analyses, together with our partner, Celgene, to understand these outcomes. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned," said Paul J. Hastings, Chairman and CEO of OncoMed Pharmaceuticals. "OncoMed remains focused on completing and analyzing the results of the two randomized Phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year and in continuing the advancement of our portfolio of biotherapeutic candidates."

OncoMed management will host a conference call today at 8:30 a.m. ET/5:30 a.m. PT to discuss the YOSEMITE clinical trial data.

Summary of Key Findings

Progression-Free Survival: The median progression-free survival (mPFS) was essentially the same across all arms of the study. For patients receiving demcizumab (either one or two truncated courses) in combination with Abraxane plus gemcitabine the mPFS was 5.5 months compared to a mPFS of 5.5 months for those in the Abraxane, gemcitabine plus placebo group (HR=0.93). In addition, no significant differences were observed when the individual treatment arms were compared to the Abraxane, gemcitabine plus placebo arm: in patients receiving a single truncated course of demcizumab the mPFS was 5.4 months (HR=1.03), and the mPFS was 5.5 months (HR=0.83) in patients receiving two truncated courses of demcizumab.

Interim Overall Survival: The interim median overall survival (mOS) for patients receiving either one or two truncated courses of demcizumab in combination with Abraxane plus gemcitabine (n =136) was 13.2 months, while a mOS was not reached for the Abraxane, gemcitabine plus placebo arm (HR=1.02). No significant differences were observed when the individual treatment arms were compared: an interim mOS of 10.6 months was observed with a single course of demcizumab (n=71) (HR=1.2) and an interim mOS of 13.3 months was seen among patients receiving two courses of demcizumab (n=65) (HR=0.87). These results are based on an analysis that occurred at the 125th PFS event at which time there were 75 deaths.

Response and Clinical Benefit Rates: Overall response rate (defined as complete responses and partial responses) was 33.1% (45 of 136 patients) in the combined demcizumab, Abraxane plus gemcitabine groups and 41.2% (28 of 68 patients) in the Abraxane, gemcitabine plus placebo group. The overall clinical benefit rate (defined as complete responses, partial responses and stable disease) was slightly higher in the pooled demcizumab arms at 74.3% (101 of 136 patients) compared to 70.6% (48 of 68 patients) in the Abraxane, gemcitabine plus placebo group. Response was measured using the RECIST 1.1 criteria and is based on unconfirmed investigator assessment.

Safety and tolerability: Demcizumab, Abraxane plus gemcitabine were generally well tolerated with nausea, diarrhea, anemia and fatigue being the most common reported toxicities. The incidence of Grade 3 or greater heart failure, pulmonary hypertension and bleeding were (3.7% vs. 0%), (0.7% vs 0%) and (8.1% vs. 1.5%) in the pooled demcizumab, Abraxane plus gemcitabine arms and the Abraxane, gemcitabine plus placebo arm, respectively.
"Pancreatic cancer has proven to be a uniquely challenging disease, and these data appear to reflect some of those disease and treatment complexities. The safety data seen in the YOSEMITE trial were generally consistent and in line with our expectations. We continue to analyze these data, and look forward to presenting the full study findings at a future scientific congress," said Robert Stagg, PharmD, Senior Vice President of Clinical Research and Development. "We would like to sincerely thank the patients and their families, investigators and staff for their support and participation in this study."

About the Phase 2 YOSEMITE Trial
The randomized Phase 2 "YOSEMITE" trial was designed to assess the efficacy and safety of demcizumab in combination with Abraxane plus gemcitabine, compared to Abraxane, gemcitabine plus placebo in first-line pancreatic cancer patients with metastatic disease. Two-hundred and seven patients were randomized and 204 patients were treated in one of three study arms: 1) Abraxane, gemcitabine plus placebo, 2) Abraxane, gemcitabine plus one 70-day truncated course of demcizumab (given once every 2 weeks with the last dose given on Day 70) or 3) Abraxane, gemcitabine plus two 70-day truncated courses of demcizumab (separated by a 98 day period without demcizumab) with the last demcizumab dose given on day 238.

The primary endpoint of YOSEMITE was progression-free survival. Secondary and exploratory endpoints were overall survival, response rate, pharmacokinetics, immunogenicity, safety and biomarker analyses. The YOSEMITE Phase 2 trial was conducted at 49 clinical sites in the U.S., Canada, Europe and Australia. OncoMed initiated YOSEMITE in April 2015 and completed enrollment of patients in September 2016.

Conference Call Today
OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to review top-line results from the Phase 2 YOSEMITE clinical trial.

Analysts and investors can participate in the conference call by dialing 1-855-420-0692 (domestic) and
1-484-756-4194 (international) using the conference ID# 5625895. A webcast of the conference call will be accessible through a link in the Investor Relations section of the OncoMed website: View Source An audio replay of the conference call can be accessed by dialing 1-855-859-2056 (domestic) or 1-404-537-3406 utilizing the conference ID number listed above. The web broadcast of the conference call will be available for replay through 90 days via the OncoMed website.

About Pancreatic Cancer
Pancreatic cancer is the third leading cause of cancer-related deaths. According to the American Cancer Society, each year in the United States there are approximately 54,000 new cases of pancreatic cancer and 43,000 deaths. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is less than one year.

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

Demcizumab is currently being studied in two randomized Phase 2 clinical trials. The YOSEMITE trial is testing demcizumab with Abraxane plus gemcitabine versus Abraxane plus gemcitabine alone in first-line advanced pancreatic cancer patients. The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients. A Phase 1b trial combining demcizumab with the anti-PD1 antibody pembrolizumab in solid tumor patients was also initiated in early 2016. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

On April 10, 2017 Redx Pharma recently presented scientific posters in oncology and fibrosis at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 1-5, 2017, in Washington D.C., USA and the Keystone Symposia (Keystone) focused on Injury, Inflammation and Fibrosis, on March 26-30, 2017, in Snowbird, Utah, USA, respectively (Press release, Redx Pharma, APR 10, 2017, View Source [SID1234524748]).

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Dr Neil Murray, Chief Executive Officer of Redx Pharma, said: The posters recently presented at key scientific congresses demonstrate that our discovery engine continues to produce the next potential therapies for high value unmet needs in oncology and immunology.

We have previously seen that Porcupine inhibitors have shown potential applications in oncology, however we are pleased that we are now able to present validated preclinical data demonstrating that they could also be efficacious against fibrosis. As a result of this we now believe there are many development opportunities in an area that has seen little meaningful therapeutic progress for patients.

Posters
Keystone
Title: Porcupine inhibitors demonstrate suitability for use as novel anti-fibrotic therapeutics
Author: Peter Bunyard
Summary: REDX06109 demonstrated a robust anti-fibrotic response when dosed therapeutically in an animal model of kidney fibrosis at levels that are expected to be well tolerated. Preliminary data also showed that Wnt ligand is a potent stimulator of human lung fibroblast proliferation and is likely to synergise with other pro-fibrotic mediators to induce an aggressive fibrotic response to tissue injury
Download the Porcupine inhibitors presentation poster

AACR
Title: Development of REDX05358, a novel highly selective and potent pan RAF inhibitor and a potential therapeutic for BRAF and RAS tumors
Author: Helen Mason
Summary: REDX05358 is a highly potent and selective inhibitor targeting all RAF isoforms, which demonstrates anti-proliferative activity across a range of mutant cancer cell lines. Unlike the first generation RAF inhibitor, vemurafenib, which only shows transient inhibitory effects in mutant RAF colorectal cancer, REDX05358 sustains inhibition of this pathway and overcomes the resistance seen with vemurafenib both in vitro and in vivo. REDX05358 presents a potential therapeutic opportunity for the treatment of mutant cancers
Download the Development of REDX05358 presentation poster

AACR
Title: Development of 2nd generation indoleamine 2,3-dioxygenase 1 (IDO-1) selective inhibitors
Author: Caroline Phillips
Summary: A novel chemical series was identified via an in silico virtual screening method with potent cellular activity against the IDO-1 enzyme, both in cancer cell lines and human dendritic cells. Experiments in dendritic cells have revealed differences between the Redx compound series and reference compounds in their inhibitory responses to varying stimulating conditions

1 * Modalities in use across pipeline and marketed products. Modality refers to the structural template of a therapeutic agent. ‡ Amgen has an additional three biosimilar programs in development which are undisclosed at this time. **Tradename provisionally approved by the United States Food and Drug Administration, This information reflects public disclosures cu rrent as of April 7, 2017. Amgen’s product pipeline will change over time as molecules move through the drug development process, including progressing to market or failing in clinical trials, due to the nature of the development process. This description contains forward-looking statements that involve significant risks and uncertainties, including those discussed in Amgen’s most recent Form 10-K and in Amgen’s periodic reports on Form 10-Q and Form 8-K, and actual results may vary materially. Amgen is pro viding this information as of the date above and does not undertake any obligation to update any forward-looking statements contained in this table as a result of new information, future events or otherwise. © 201 7 Amgen Inc. All rights reserved. 33 pre clinical and clinical targets with STRONG GENETIC SUPPORT The industry’s largest toolkit with 13 MODALITIES* A mix of INNOVATIVE MOLECULES, NEW INDICATIONS, AND BIO SIMILARS A robust and differentiated pipeline, leveraging state-of-the-art science to create medicines for serious illness. Amgen is focused on high-quality candidates that demonstrate large, clinically-relevant effects. Human genetic validation is used whenever possible to enhance the likelihood of success. BIOSIMILARS ‡ ABP 215 (biosimilar bevacizumab) Hematology/ Oncology ABP 494 (biosimilar cetuximab) Hematology/ Oncology ABP 710 (biosimilar infliximab) Inflammation ABP 798 (biosimilar rituximab) Hematology/ Oncology & Inflammation ABP 959 (biosimilar eculizumab) Hematology /Oncology ABP 980 (biosimilar trastuzumab) Hematology/ Oncology PHASE ONE PHASE TWO PHASE THREE AMG 176 Hematology/ Oncology AMG 211 Hematology/ Oncology AMG 224 Hematology/ Oncology AMG 899 Cardiovascular BLINCYTO (blinatumomab) Hematology/ Oncology Erenumab Neuroscience AMG 520 Neuroscience Aranesp (darbepoetin alfa) Hematology/ Oncology BLINCYTO (blinatumomab) Hematology/ Oncology AMG 301 Neuroscience AMG 330 Hematology/ Oncology AMG 420 Hematology/ Oncology Tezepelumab Inflammation Enbrel (etanercept) Inflammation Erenumab Neuroscience **EVENITY TM (romosozumab) Bone Health AMG 557 Inflammation AMG 570 Inflammation AMG 592 Inflammation IMLYGIC (talimogene laherparepvec) Hematology/ Oncology KYPROLIS (carfilzomib) Hematology/ Oncology Omecamtiv mecarbil Cardiovascular AMG 820 Hematology/ Oncology AMG 986 Cardiovascular IMLYGIC (talimogene laherparepvec) Hematology/ Oncology Prolia (denosumab) Bone Health Repatha (evolocumab) Cardiovascular Vectibix (panitumumab) Hematolog y/ Oncology KYPROLIS (carfilzomib) Hematology/ Oncology Oprozomib Hematology/ Oncology XGEVA (denosumab) Hematology/ Oncology 2 * Modalities in use across pipeline and marketed products. Modality refers to the structural template of a therapeutic agent. ‡ Amgen has an additional three biosimilar programs in development which are undisclosed at this time. This information reflects public disclosures current as of April 7, 2017. Amgen’s product pipeline will change over time as molecules move through the drug development process, including progressing to market or failing in clinical trials, due to the nature of the development process. This description contains forward-looking statements that involve significant risks and uncertainties, including those discussed in Amgen’s most re cent Form 10-K and in Amgen’s periodic reports on Form 10-Q and Form 8-K, and actual results may vary materially. Amgen is providing this information as of the date above and does not undertake any obligation to update any forward-looking statements contai ned in this table as a result of new information, future events or otherwise. © 201 7 Amgen Inc. All rights reserved. PHASE ONE Phase 1 clinical trials investigate safety and proper dose ranges of a product candidate in a small number of human subjects. MOLECULE NAME & PRONUNCIATION MODALITY THERAPEUTIC AREA DESCRIPTION AMG 176 Small Molecule Hematology/ Oncology AMG 176 is a small molecule being investigated as a treatment for multiple myeloma. AMG 211 BiTE A ntibody Hematology/ Oncology AMG 211 is an anti-CEA x anti-CD3 (BiTE ) bispecific antibody construct. It is being investigated as a treatment for various cancer types. AMG 211 is being jointly developed in collaboration with MedImmune. AMG 224 Antibody Drug Conjugate Hematology/ Oncology AMG 224 is an antibody drug conjugate being investigated for the treatment of multiple myeloma. AMG 301 Monoclonal Antibody Neuroscience AMG 301 is a human monoclonal antibody that inhibits the type 1 receptor of the pituitary adenylate cyclase-activating polypeptide (PAC1). It is being investigated for migraine prevention. AMG 301 is being jointly developed in collaboration with Novartis. AMG 330 BiTE Antibody Hematology/ Oncology AMG 330 is an anti-CD33 x anti-CD3 (BiTE ) bispecific antibody construct. It is being investigated as a treatment for acute myeloid leukemia. AMG 420 BiTE Antibody Hematology/ Oncology AMG 420 is an anti-BCMA x anti-CD3 (BiTE ) bispecific antibody construct. It is being investigated as a treatment for multiple myeloma. AMG 557 Monoclonal Antibody Inflammation AMG 557 is a human monoclonal antibody that inhibits the action of B7 related protein (B7RP-1). It is being investigated as a treatment for systemic lupus erythematosus. AMG 557 is being jointly developed in collaboration with AstraZeneca. AMG 570 Bispecific Antibody Inflammation AMG 570 is a bispecific antibody-peptide conjugate that targets BAFF and ICOSL. It is being investigated as a treatment for systemic lupus erythematosus. AMG 570 is being jointly developed in collaboration with AstraZeneca. AMG 592 Fusion Protein Inflammation AMG 592 is an IL-2 mutein Fc fusion protein. It is being investigated as a treatment for inflammatory diseases. AMG 820 Monoclonal Antibody Hematology/ Oncology AMG 820 is a human monoclonal antibody that inhibits c-fms and decreases tumor-associated macrophage (TAM) function. It is being investigated as a treatment for various cancer types. AMG 986 n/a Cardiovascular AMG 986 is being investigated for the treatment of heart failure. IMLYGIC (t alimogene laherparepvec) tal im’ oh jeen la her" pa rep’ vek Oncolytic Immunotherapy Hematology/ Oncology IMLYGIC is an oncolytic immunotherapy derived from HSV-1. It is being investigated as a combination treatment in patients with mid-to late-stage metastatic melanoma (Phase 1b/3) and in other cancer types (Phase 1).

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On April 7, 2017 REGiMMUNE Corporation reported the closing of a Series E financing on April 7th (Press release, REGimmune, APR 7, 2017, View Source [SID1234642231]). The company raised 6 million US in this new round, which was led by SMBC Venture Capital Co., Ltd., the VC arm of Sumitomo Mitsui Banking Corporation(SMBC) and Japan Asia Investment Corporation (JAIC). Additional investors participating in this round are new investors Miyako Capital,Iyo-Gin Capital, Oita Venture Capital, Kyoritsu Captal,Hiroshima Venture Capital and several individual investors. Existing investors, and Mitsubishi UFJ Bank Capital also invested in this financing. Proceeds from this funding will be used clinical　study in US.

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REGiMMUNE successfully completed a Phase I/2a study of RGI-2001 for Graft versus Host Disease (GvHD) . Data from the Phase I/2a study showed no safety concerns up to the highest dose and some preliminary signs of efficacy were observed.

Kenzo Kosuda, President and Chief Executive Officer, said "We now have positive human clinical data that validates the usefulness of our immune-regulating technology platform. The financing announced today will allow us to start an addinotal clinical study to gain the more human data."

On April 5, 2017 APAC Biotech, reported that it was granted with a commercial license by Indian FDA (CDSCO – Central Drugs Standard Control Organization) to market product, APCEDEN, a Dendritic cell-based autologous Immuno-oncology product for four cancer indication namely Prostate, Ovarian, Colo-rectal and Non Small Cell Lung carcinoma (Press release, APAC Biotech, APR 5, 2017, View Source [SID1234562370]).

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The Indian Food and Drug Administration authorities, after their stringent review of the application, have issued the commercial license (Form 46) to conduct a post marketing surveillance on statistically significant number of patients for each indication.

Other products namely STEMPEUCEL, an allogeneic-cultured mesenchymal cells from Stempeutics and OSSORON, an autologous-cultured adult osteoblast and CHONDRON, an autologous-cultured adult chondrocyte from Regenerative Medical Services, Mumbai, also received the marketing license at the same time.

"The past decades have seen revolutionary progress in the development and application of cell and genetic engineering in an effort to personalize the treatment of cancer. We are now confident that it is possible to treat cancer patients using this approach as observed during clinical trials across India. The results are encouraging and mark a potential new paradigm in treating these solid tumors that do not respond to standard therapies," said a leading oncologist, Dr. Ashok Vaid.

APCEDEN, an autologous monocyte-derived mature Dendritic cell when loaded with tumor antigen have the ability to generate an effective immune response against the tumor. In the year 2011, an ATTEST trial was conducted where refractory solid tumor with multiple chemo failure patients were enrolled and administered with APCEDEN. The results were published in International Journal of Cytotherapy in the year 2014. ATTEST study included a stringent logistics management and was uniquely, effectively, conducted under the leadership of Principal investigator, Medical oncologist, Dr. P P Bapsy.

The trial was designed to understand the potential benefits and risk of the therapy. In the trial 28.9% of cases showed stability of disease with good quality of life. A retrospective study was also conducted on the advice of CBBTDEC (Cell Biology Based Therapeutic Drug Evaluation Committee), ICMR (Indian Council of Medical Research) where more than 200 days’ of survival benefit was observed as compared to the retrospective control group.