On April 16, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that it has entered a new worldwide collaboration with Bristol-Myers Squibb Company on a program to develop and commercialize Factor XIa (FXIa) inhibitors, including BMS-986177, for the prevention and treatment of major thrombotic conditions (Press release, Johnson & Johnson, APR 16, 2018, View Source [SID1234525347]). Under the agreement, Janssen Pharmaceuticals, Inc. and Bristol-Myers Squibb Company will advance BMS-986177 into Phase 2 clinical trials and establish a broad development program across multiple therapeutic indications.

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The development of novel oral anticoagulants has been a major step forward in the prevention and treatment of thrombosis. The goal for next-generation anticoagulants is to achieve the same efficacy as the current standard of care while substantially lowering the risk of bleeding. Early clinical research has shown that

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FXIa inhibition has the potential to reduce the risk of thrombotic events with a significantly lower risk of bleeding compared to currently available therapies.

"Janssen has built deep knowledge in the anticoagulation space through our extensive experience researching and developing innovative cardiovascular therapies," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Janssen Research & Development, LLC. "We look forward to applying our expertise to this collaboration with Bristol-Myers Squibb to explore the full potential of BMS-986177 through Factor XIa inhibition to provide a wider safety window for anticoagulation than current therapies."

"With the addition of a Factor XIa inhibitor program to our pipeline, Janssen continues to live up to our long-standing commitment of working tirelessly to bring truly transformational therapies to patients worldwide," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "With this new collaboration we have the potential to improve the standard of care for patients with cardiovascular conditions characterized by pathologic thrombosis."

The companies will share development costs and commercial profits and losses. Additional terms of the agreement were not disclosed

On April 16, 2018 VBL Therapeutics (NASDAQ:VBLT) reported that its presented a late-breaking study demonstrating a novel bi-specific antibody that induces immune-cell mediated killing of cancer cells through binding to a tumor membrane receptor, MOSPD2 (Press release, VBL Therapeutics, APR 16, 2018, View Source [SID1234525364]). Data are presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting in Chicago, Illinois

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.
"Selective targeting of tumor cells is challenging, as it requires a tumor-specific receptor, or process, that can be attacked without compromising safety. Our new data demonstrate that different solid tumors show high expression of MOSPD2 as it likely supports their ability to invade and metastasize. Our bi-specific antibody is taking advantage of this tumor-specificity to induce killing of tumor cells. We continue to advance our exciting VB-600 series of antibodies as drug candidates for oncology and inflammatory indications," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics.

VBL research has identified MOSPD2 (Motile Sperm Domain-containing Protein 2) as a protein involved in cell motility. Previously, the Company published data on the involvement of MOSPD2 in immune cell migration, and new data presented today at AACR (Free AACR Whitepaper) show high and selective MOSPD2 expression by multiple tumor types along with involvement of MOSPD2 in tumor cell invasiveness. In addition, a novel bi-specific antibody that was engineered to bridge interaction of T-cells with tumor cells, via binding to the T-cell protein CD3 and the tumor receptor MOSPD2, induced T-cell activation and resulted in the killing of cancer cells in a pre-clinical setting.
These data provide proof-of-concept for the use of antibody-mediated killing of MOSPD2-expressing cancer cells, with potential applicability to solid tumors and myeloid malignancies. VBL is developing its VB-600 series of antibodies targeting MOSPD2 for oncology and inflammatory applications.
For VBL’s poster presentation at AACR (Free AACR Whitepaper) kindly see the following link.

On April 16, 2018 Only a couple weeks after Takeda Pharmaceuticals reported it was interested in buying Shire, Shire sells its oncology business to France’s Servier for $2.4 billion (Press release, BioSpace, APR 16, 2018, View Source [SID1234525333]).

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It’s possible the sale will make Shire less desirable for Takeda, since Shire’s oncology business was part of the rationale for buying the company. It’s also possible it will make it more desirable by dropping the price slightly. Reuters notes, "The [Servier} deal suggests there is value locked up within Shire’s portfolio—despite a dismal share price performance in the past two years—as its management braces for a possible $50-billion bid battle with Japan’s biggest drugmaker."

Shire has suggested the proceeds from the sale may be returned to shareholders via a buyback. It also indicated that further sales of non-strategic assets were a possibility.
Shire is making it clear that is began looking to sell its oncology business in December and began the sale process in January. In other words, they want it understood that they didn’t quickly sell off the cancer unit to fend off an unwanted Takeda acquisition.

Under UK acquisition laws, Takeda has until April 25 to announce an official bid. The market value of Shire is about $47 billion. Reuters writes, "Buying Shire would be transformational for Takeda but would be a huge financial stretch, since the company is worth around $10 billion more than the Japanese group. Shire also had debt of around $19 billion as of the end of 2017."

Shire’s oncology business includes products such as Oncaspar (pegaspargase), part of a multi-agent treatment for acute lymphoblastic leukemia (ALL) and ex-U.S. rights to Onivyde (irinotecan pegylated liposomal formulation), part of a multi-agent treatment for metastatic pancreatic cancer after gemcitabine-based therapy, and Calaspargase Pegol (Cal-PEG), which is currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of ALL and early stage immuno-oncology pipeline collaborations.

"This transaction is a key milestone for Shire, demonstrating the clear value embedded in our portfolio," said Flemming Ornskov, Shire’s chief executive officer, in a statement. "While the Oncology business has delivered high growth and profitability, we have concluded that it is not core to Shire’s longer-term strategy. We will continue to evaluate our portfolio for opportunities to unlock further value and sharpen our focus on rare disease leadership with selective disposals of non-strategic assets."
Last year the Oncology business created revenues of $262 million.

If Takeda does make an official bid for Shire, this sale might make it slightly more affordable. Last year Takeda acquired Ariad Pharmaceuticals for $4.7 billion. "Shire’s decision to buy back shares may also indicate a positive view of the bid, since increasing shareholder returns would make it easier to get approval for a deal, Kazuyoshi Saito, a senior analyst for Iwai Cosmo Securities Co." told Bloomberg in a phone interview. "I have an impression that Takeda and Shire are heading in the same direction," Saito said.

Meanwhile, buying Shire’s oncology business bolster’s Servier’s presence in oncology. Olivier Laureau, Servier Group President, said in a statement, "The acquisition of Shire’s oncology franchise enables Servier to meet its strategic ambitions to become a global key player in oncology. As an essential step in the evolution of the Group, this acquisition allows us to establish a direct commercial presence in the United States, the world’s leading pharmaceuticals market, and to strengthen our portfolio of marketed products in the territories where Servier is already present. Our goal is to bring these treatments to greater numbers of cancer patients around the world. We thoroughly look forward to welcoming Shire’s oncology teams who will join Servier after the closing."

On April 16, 2018 Humanigen, Inc. (OTCQB: HGEN), a biopharmaceutical company pursuing cutting-edge science to develop its proprietary monoclonal antibodies for immunotherapy and oncology treatments, reported it has signed an agreement with The University of Texas MD Anderson Cancer Center to begin investigator-led research on lenzilumab and its potential to support chimeric antigen receptor T cell (CAR-T) therapy (Press release, Humanigen, APR 16, 2018, View Source [SID1234525348]). Lenzilumab is a first-in-class Humaneered recombinant monoclonal antibody that targets and is an antagonist of soluble granulocyte-macrophage colony-stimulating factor (GM-CSF).

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Preclinical work assessing lenzilumab’s action on one of the mechanisms in the inflammatory cascade induced by CAR-T will proceed in parallel with a planned study that could potentially qualify as a registration study, testing lenzilumab as a potential prophylaxis for neurotoxicity induced by CAR-T therapy. Neutralization of circulating GM-CSF has the potential to blunt or prevent an inflammatory cascade that can result in serious and life-threatening CAR-T-induced side effects – neurotoxicity and Cytokine Release Syndrome.

"With this agreement, we are excited that the team at MD Anderson Cancer Center is beginning to investigate lenzilumab’s potential to make groundbreaking CAR-T therapy safer, better and more routine," said Cameron Durrant, M.D., chairman and chief executive officer of Humanigen. "CAR-T science has moved quickly in the past few years with the two currently marketed CAR-T therapies having been approved based on single Phase 1/2 studies. We look forward to adding to the burgeoning, cutting-edge science studying lenzilumab as a potential critical CAR-T support therapy."

The preclinical study will measure the ability of lenzilumab to block patient CD19-CAR-T cells-treatment-derived GM-CSF induction of human leukocyte antigen-DR (HLA-DR) expression on CD14+ monocytes. It will assess the inhibitory effect of lenzilumab on GM-CSF-induced HLA-DR expression on CD14+ cells, plus other phenotypic and functional monocyte assays.

About Lenzilumab

Lenzilumab is a first-in-class, novel Humaneered recombinant monoclonal antibody designed to target and neutralize circulating granulocyte-macrophage colony-stimulating factor (GM-CSF), the myeloid inflammation factor involved in the recruitment of myeloid cells to a tumor and a central actor in leukocyte differentiation, autoimmunity and inflammation. There is also extensive evidence linking GM-CSF expression to serious and potentially life-threatening side effects in chimeric antigen receptor T-cell (CAR-T) therapy, such as neurotoxicity and Cytokine Release Syndrome (CRS). Humanigen is working with leading CAR-T experts to develop lenzilumab as a potential prophylactic treatment to minimize neurotoxicity associated with CAR-T cancer therapy. In addition, lenzilumab is currently being evaluated as a potential treatment for rare leukemias in a phase 1 trial (NCT02546284) in patients with chronic myelomonocytic leukemia (CMML) with additional potential in juvenile myelomonocytic leukemia (JMML), a rare pediatric cancer. In previous clinical trials, lenzilumab has shown to be safe and well-tolerated in more than 100 patients, including those with rheumatoid arthritis, asthma and healthy volunteers. It is a potent inhibitor of GM-CSF in vivo.

On April 16, 2018 Bristol-Myers Squibb Company (NYSE: BMY) reported two-year overall survival (OS) data from CheckMate -141, a Phase 3 open-label, randomized trial evaluating Opdivo (nivolumab) compared with investigator’s choice chemotherapy (cetuximab, docetaxel or methotrexate) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after failure on platinum-based therapy (Press release, Bristol-Myers Squibb, APR 16, 2018, View Source [SID1234525334]). Patients treated with Opdivo experienced a 32% reduction in the risk of death after a minimum two years of follow-up (HR 0.68; 95% CI: 0.54 to 0.86), with a median OS of 7.7 months (95% CI: 5.7 to 8.8) compared with 5.1 months (95% CI: 4.0 to 6.2) for standard chemotherapy. The two-year survival rate for Opdivo was 16.9% (95% CI: 12.4 to 22.0) versus 6.0% (95% CI: 2.7 to 11.3) for standard chemotherapy. The safety profile for Opdivo at two-year follow-up was consistent with previous analyses from the study.

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These data will be presented today as an oral presentation (Abstract #CT116) at 4:35 PM CDT, N Hall C (Level 1) during the Updates in Immuno-Oncology Trials session at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago.

"The introduction of Immuno-Oncology has the potential to change the treatment landscape of squamous cell carcinoma of the head and neck, compared with the standard of care," said Robert L. Ferris, M.D., Ph.D., a cancer immunotherapist and Director, UPMC Hillman Cancer Center, Pittsburgh, PA. "The sustained overall survival benefit demonstrated by nivolumab in this study is encouraging in SCCHN, which historically has a median survival of less than six months."

The sustained Opdivo OS benefit was observed across PD-L1 expressors and non-expressors in patients with recurrent or metastatic SCCHN. At the two-year follow-up in patients treated with Opdivo whose tumors had PD-L1 expression ≥ 1%, risk of death was reduced by 45% (HR 0.55; 95% CI: 0.39 to 0.78). For patients treated with Opdivo whose tumors had PD-L1 expression <1%, risk of death at two years was reduced by 27% (HR 0.73; 95% CI: 0.49 to 1.09) versus standard chemotherapy.

"Opdivo is the only I-O treatment for squamous cell carcinoma of the head and neck to have shown a significant overall survival benefit versus chemotherapy at the primary analysis. These two-year follow-up data show a sustained long-term overall survival benefit for patients, across PD-L1 expression levels and regardless of HPV status," said Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb. "These data showing the durability of this benefit reinforce our ongoing commitment to continuing research with the hope of delivering what matters most to patients fighting cancer: long-term survival."

There were no statistically significant differences between the two arms for PFS (HR 0.87; 95% CI: 0.68 to 1.11) for Opdivo and investigator’s choice, respectively. The safety profile of Opdivo with a two-year follow-up was consistent with previous analyses and with prior studies of Opdivo in patients with melanoma and non-small cell lung cancer. Grade 3-4 treatment-related adverse reactions occurred in 15.3% of patients receiving Opdivo versus 36.9% of patients receiving investigator’s choice.

About CheckMate -141 (Abstract #CT116)
CheckMate -141 is a global phase 3, open-label, randomized trial evaluating Opdivo versus investigator’s choice chemotherapy in patients with recurrent or metastatic SCCHN who had tumor progression during or within six months of receiving platinum-based therapy administered in the adjuvant, neo-adjuvant, primary (unresectable locally advanced) or metastatic setting. Patients were included regardless of their HPV or PD-L1 status. Patients were randomized 2:1 to receive Opdivo 3 mg/kg intravenously over 60 minutes every two weeks (n=240), or investigator’s choice (n=121) of methotrexate 40 to 60 mg/m2 intravenously weekly, docetaxel 30 to 40 mg/m2 intravenously weekly, or cetuximab 400 mg/m2 intravenously once then 250 mg/m2 weekly. The primary endpoint is OS. The trial’s secondary endpoints include progression-free survival (PFS) and objective response rate (ORR).

About Head & Neck Cancer
Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers, with global incidence expected to increase by 17% between 2012 and 2022. Risk factors for SCCHN include tobacco and alcohol consumption. The human papillomavirus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America. Quality of life is often impacted for SCCHN patients, as physiological function (breathing, swallowing, eating, drinking), personal characteristics (appearance, speaking, voice), sensory function (smell and hearing), and psychological/social function can be affected.