On May 2, 2018 The Mundipharma global network of independent associated companies reported that Herzuma, biosimilar trastuzumab, is now available in Europe, with the product now launched in both the UK and Germany and further launches across European countries anticipated in the coming months (Press release, Mundipharma, MAY 2, 2018, View Source [SID1234526137]). The Mundipharma network has exclusive distribution rights to Herzuma in the UK, Germany, Italy, Ireland, Belgium, Luxembourg and the Netherlands.

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Richard Trollope, Head of Oncology and Biosimilars at Mundipharma International Limited, said: "Building on our partnership with Celltrion Healthcare, we are pleased to announce that biosimilar trastuzumab is now available in Europe with national launches commencing in both the UK and Germany. The availability of biosimilar trastuzumab will provide an alternative treatment option to the thousands of eligible patients across Europe with early breast cancer, metastatic breast cancer or metastatic gastric cancer."

Herzuma, a biosimilar of i.v. Herceptin, was granted marketing authorisation on 9th February 2018 for the treatment of patients with early breast cancer, metastatic breast cancer or metastatic gastric cancer whose tumours have either HER2 overexpression or HER2 gene amplification, following positive opinion and recommendation for approval by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in December 2017. Biosimilar trastuzumab has the potential to make significant cost savings for healthcare organisations, releasing healthcare resource for other innovative medicines.3

Alberto Martinez, President and CEO, Mundipharma International Limited, said: "Mundipharma has a proven track record of launching biosimilars successfully in Europe, which is illustrated by Celltrion Healthcare entrusting us once again with the launch of biosimilar trastuzumab across key European markets. As biosimilar trastuzumab continues to launch in additional countries, we look forward to assisting healthcare economies across Europe wanting to deliver better value to patients."

Herzuma is the third biosimilar to be marketed and distributed by the Mundipharma network in Europe, having launched Remsima (infliximab), the first biosimilar monoclonal antibody, in 2015, and Truxima (rituximab), the first biosimilar monoclonal antibody for the treatment of cancer, in 2017.

On May 2, 2018 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that company management will present at two investor conferences in May (Press release, Iovance Biotherapeutics, MAY 2, 2018, View Source;p=RssLanding&cat=news&id=2346318 [SID1234525942]):

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Deutsche Bank’s 43rd Annual Health Care Conference in Boston, MA on Tuesday, May 8, 2018 at 2:50 p.m. ET
UBS Global Healthcare Conference in New York, NY on Monday, May 21, 2018 at 2:30 p.m. ET
A live audio webcast of both presentations will be available by visiting the Investors section of Iovance Biotherapeutics’ website at View Source A replay of the webcasts will be archived on Iovance Biotherapeutics’ website for 30 days following the presentations.

On May 2, 2018 Exelixis, Inc. (Nasdaq: EXEL) reported that it has entered into a collaboration with Invenra, Inc., the Madison, Wisconsin-based biotechnology firm focused on developing next-generation biologics, to discover and develop multispecific antibodies for the treatment of cancer (Press release, Exelixis, MAY 2, 2018, View Source;p=RssLanding&cat=news&id=2346478 [SID1234525962]). The partnership pairs Exelixis’ fundamental biological insights, clinical development prowess and commercialization expertise with Invenra’s innovative platform technologies and biologics expertise to identify, optimize, and manufacture multispecific therapeutics, including immunotherapy applications. The collaboration is part of Exelixis’ ongoing strategy to build an innovative pipeline beyond its two internally discovered, commercially available compounds, cabozantinib and cobimetinib. The agreement with Invenra creates a biologics discovery capability that complements Exelixis’ in-house small molecule drug discovery efforts.

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This press release features multimedia. View the full release here: View Source

Under the terms of the agreement, Exelixis and Invenra will collaborate to discover and develop multispecific antibodies through the use of Invenra’s B-Body technology platform, which enables high-throughput discovery, functional screening, and in vitro and in vivo preclinical characterization of promising therapeutic candidates. Invenra will be responsible for antibody lead discovery and generation. Exelixis will lead investigational new drug (IND)-enabling studies, manufacturing, clinical development in single-agent and combination therapy regimens, as well as future regulatory and commercialization activities.

"Partnering with Invenra to leverage its deep expertise in protein engineering and the discovery of multispecific antibodies is an important step toward adding proprietary biologics to the Exelixis pipeline," said Peter Lamb, Ph.D., Executive Vice President, Discovery Research and Chief Scientific Officer of Exelixis." We are excited to work with the Invenra team and have structured our collaboration to provide relatively small financial support upfront and pay for success down the road. As we rebuild our internal small molecule discovery capability, this partnership provides a complementary approach that enables us to target pathways not accessible to small molecules, increasing our ability to advance novel therapies into the clinic."

Under the collaboration agreement, Exelixis will receive an exclusive, worldwide license to one preclinical asset, and Exelixis and Invenra intend to pursue up to six additional discovery projects during the term of the collaboration, which in total are directed to three discovery programs. In consideration for the exclusive worldwide license and other rights contained in the collaboration agreement, Exelixis will pay Invenra an upfront payment of $2.0 million plus $2.0 million at initiation of each discovery project. Invenra is eligible to receive payments of up to $131.5 million based on the achievement of specific pre-clinical, clinical development and regulatory milestones for any product containing a lead preclinical asset in the first indication. Upon successful commercialization of a product, Invenra is eligible to receive global milestone payments up to $325 million, if certain sales thresholds are achieved as well as single digit tiered royalties on net sales of the approved product.

"We’re very excited to partner with Exelixis on this multi-asset collaboration as the company moves beyond its small molecule expertise to build a biologics pipeline," said Roland Green, Ph.D., Chief Executive Officer and Co-Founder of Invenra. "Invenra’s B-Body platform has been validated internally. Our innovative technologies to discover, characterize, and generate multispecific antibodies pair well with Exelixis’ demonstrated success in oncology clinical development and commercialization. We look forward to working together with the Exelixis team to bring forward potential new anti-cancer therapies."

About Invenra

Invenra, Inc., is a biotechnology company focused on the discovery and development of multispecific antibodies for immuno-oncology. Invenra’s proprietary B-Body and SNIPER technologies are used to develop novel antibodies that can bind to two or more specific therapeutic targets and mimic the natural IgG antibodies made by the human body. The B-Body platform enables the rapid identification of an optimal combination of epitope, affinity and geometry of an antibody using high throughput in-format screening for function in cell-based assays, while maintaining the biophysical characteristics needed for lead development. Importantly, the B-Body platform is designed to create advantages for candidate discovery with novel mechanisms of action and ease of manufacturing. Invenra has developed its own pipeline of lead multispecific antibodies and has partnered with several biotechnology and pharmaceutical companies who leverage Invenra’s technologies to identify molecules with biological relevance for drug development. For more information, please visit www.invenra.com.

On May 2, 2018 Refuge Biotechnologies, Inc. ("Refuge"), a company leveraging gene engineering technologies to develop intelligent cell therapeutics programmed to make decisions inside of patients, reported the closing of a $25 million Series B investment round (Press release, refuge biotechnologies, MAY 2, 2018, View Source [SID1234525981]). In addition, the company has appointed immuno-oncology pioneer Francesco Marincola, M.D., as chief scientific officer.

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The Series B financing was led by 3SBio and Sequoia China, with participation from new investors Danhua Capital (DHVC), Sangel Capital and Ocean Pine Healthcare Fund. Refuge’s existing investors, 3E Bioventures, WuXi Healthcare Ventures, and ShangBay Capital, also participated in the round.

The funds from the Series B will support advancement of cell therapies developed with Refuge’s receptor-dCas platform, which utilizes a mutated or dead Cas9 (dCas) as a targeting mechanism to enable precision CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi). The cell therapies are programed to only activate CRISPRa/CRISPRi when they encounter specific sensors found on the surface of cancer cells, which delivers the treatment effect only to target cells. As a result, cell therapies have the potential to bring together multiple anti-cancer approaches in a single cell, such as repression of multiple checkpoint targets, with greater potency and reduced side effects. Refuge’s pipeline is led by RB-1916, a CAR-T cell therapy designed to inhibit the expression of the PD-1 gene, with a potential initial application in diffused large B-cell lymphoma. Refuge has additional CAR cell therapy programs under research that conditionally repress PD-1 and other checkpoint inhibitors for potential treatment of solid tumors.

"We have seen tremendous progress in the development of our technology and science, and believe that our receptor-dCas platform has the potential to create highly targeted cell therapies that bring superior efficacy while overcoming limitations related to toxic side effects," said Bing C. Wang, Ph.D., co-founder and chief executive officer of Refuge Biotech. "This financing will propel our efforts with our growing pipeline as we continue to design these innovative and intelligent cell therapies to fight cancer, and we are encouraged by the support from this top group of global investors."

As part of the investment, the lead investors will have an exclusive right to negotiate with Refuge on the right to the development and commercialization of cell therapies using Refuge’s platform in China. Concurrently, Refuge and 3SBio will also collaborate on research developing programmed cell therapeutics that can produce therapeutic proteins inside a patient’s body using Refuge’s platform technology.

Concurrent with the financing, Zhenping Zhu, M.D., Ph.D., of 3SBio and Trency Gu, Ph.D., of Sequoia China, have joined the Refuge board of directors.

"3SBio’s investment demonstrates our commitment to advancing cutting-edge gene engineering technologies with potential for breakthrough treatments for cancer and other diseases with unmet medical needs," said Jing Lou, M.D., Ph.D., Chairman and CEO of 3SBio Inc. "3SBio looks forward to collaborating with Refuge to accelerate the clinical development of Refuge’s next-generation cell therapies for cancer and to fully realize the potential of the dCas9 platform."

Added Neil Shen, founding and managing partner of Sequoia China, "Sequoia China endeavors to back innovative companies in the life science field such as Refuge Bio, which brings together topnortch scientific and commercial talents in the gene editing and cell therapy space. We are pleased to support Refuge Bio to further develop the dCas9 platform for wide therapeutic applications to improve human health."

The CRISPRa and CRISPRi are made possible by dCas9, which no longer cuts DNA but functions as a carrier to specific areas of the genome for highly targeted delivery a transcriptional activator or repressor to turn on or turn off genes. The novel receptor-dCas platform allows for control of how a cell interacts with its environment. Cells generally communicate and sense their surrounding through membrane receptors. Connecting receptors to dCas creates a therapeutic platform that enables cells to sense its surroundings and activate or repress multiple gene expression based on the receptor-ligand interactions. With receptor-dCas, cells can be now programmed to turn off certain genes, such as PD-1, to generate more potent CAR-T immune cells when it senses the presence of a tumor cell.

About Francesco Marincola, M.D.
As chief scientific officer, Dr. Marincola will lead development of Refuge’s intelligent cell therapy platform and investigation of its lead therapeutic programs. He most recently served as a distinguished research fellow and strategist for immune oncology discovery at AbbVie. Prior to this, he developed and led a genetic research institute at Sidra Medical and Research Center in Qata where he played a pivotal role in the Qatar Genome Project. He also trained in surgical oncology under Steven Rosenberg, M.D., Ph.D., at the National Cancer Institute and subsequently was a tenured investigator and chief of the infectious disease and immunogenetics section at the NIH Clinical Center. Dr. Marincola has spent his career studying tumor immunology and was a pioneer in the development of technologies for studying in real-time the dynamics of the tumor microenvironment adaptations during immune therapy. He described the mechanisms leading to cancer immune rejection describing the immunologic constant of rejection as a conserved process shared responsible for other forms of immune-mediated tissue-specific destruction such as allograft rejection, graft versus host disease, flares of autoimmunity and clearance of pathogen during acute infections. He is currently leading worldwide efforts to understand the mechanism of cancer immune resistance such as the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Task Force on Immune Responsiveness aimed at involving different areas of expertise besides immunology. Dr. Marincola graduated summa cum laude at the University of Milan, Medical School, Italy, and completed a general surgery residency with a focus in immunology at Stanford University. He was president of the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and is the founding and current editor-in-chief of the Journal of Translational Medicine.

On May 2, 2018 EpicentRx, a San Diego biotechnology company developing a next-generation immunotherapy platform of viruses that infect and kill cancer cells for the treatment of several tumor types, reported that it has developed the first ever series of oncolytic viruses tailored to tumors of individual patients (Press release, EpicentRx, MAY 2, 2018, View Source [SID1234528889]). The first patient, treated at the University of Cincinnati (UC) in Cincinnati, Ohio, by John Morris, MD, professor at the UC College of Medicine and director of the area’s only Phase I/Experimental Therapeutics Program, has been enrolled to receive a personalized virus that has been "armed" with peptide fragments or neoantigens from his specific tumors.

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Neoantigens are ideal targets for the immune system because they are selectively expressed on tumors not on normal cells. Viruses naturally target and kill cancer cells and these personalized viruses, which are derived from viruses that cause the common cold, have been engineered to improve on that ability since they use the machinery of the cancer cell to produce thousands of copies of themselves and the neoantigens that they are carrying. Hence, these viruses are administered with the goal of training the immune system to seek out and destroy the cancer cells that display these neoantigens.

This trial "provides proof-of-principle that personalized viral vaccines tailored and targeted to patient tumors can be made quickly and on demand," said Dr. Tony R. Reid, Chief Scientific Officer of EpicentRx and Associate Professor of Oncology at UCSD in California.

Dr. Corey A. Carter, CEO of EpicentRx, added that while current treatment paradigm in oncology relies on off the shelf, one size fits all therapies, "we know that every patient and patient’s tumor is different. To target an individual tumor in individual patients is nothing short of a revolution."

Drs. Carter and Reid felt that further development of personalized viral vaccines is warranted in combination with other immunotherapy weapons such as checkpoint inhibitors, which also trigger immune responses against cancer neoantigens, albeit non-specifically. "The reality is that other immunotherapies, such as checkpoint inhibitor drugs, only benefit 20-25% of patients in selected tumor types. There’s nothing for the other 75-80% of patients that don’t benefit. We can and must do better. These viruses are potentially a way to increase response rates so that the other 75-80% of patients start to benefit," said Dr. Carter.

"No two cancer cells are exactly alike, making it difficult to target cancer cells with drugs that inhibit one receptor or even one pathway since the cancer cells may and often do vary with respect to genetic changes and survival mechanisms," says Dr. Morris. "This personalized viral vaccine has the ability to contain express many different neoantigens from the tumor, targeting multiple genetic mutations in tumor cells, which could potentially prevent the cancer cells from sidestepping the immune system. We are excited to be part of this trial, which could prove beneficial for many patients."

"When you infect a cancer cell with a virus, it is like waving a big red flag at a bull, which stimulates the immune system to ‘go after’ the cancer. But like a matador cancer often has the ability to maneuver away from the threatening attack. In our experiments we have found that when the virus is personalized to the tumor with multiple neoantigens, the tumor is unable to escape the immune system’s charge and is ‘gored’," said Dr. Reid. "Effectively what we are doing with these viruses is to use the immune system’s natural ability to attack many target antigens, which is what happens every time we get an infection."

Oncolytic viruses have been tested in thousands of patients in the clinic and generally appear to only cause flu-like symptoms for about a week, according to Dr. Reid.

The viruses were manufactured in house according to Good Manufacturing Practice (GMP) regulations and samples of patient tumors and normal DNA from blood underwent whole-exome sequencing to reveal mutations present only in the tumor.

According to Dr. Carter, "Future personalized viral vaccine trials will be done under a separate Investigational New Drug application to the FDA, so many more patients with advanced disease may be enrolled to test the efficacy of the viruses both alone and with checkpoint blockade and other immunotherapeutics. Personalized viruses have the potential to be applied to any cancer with enough neoantigens for vaccination."

Tumor-targeting viruses can rally the immune system against cancers, boosting the efficacy of immunotherapy drugs and opening the door to promising combination treatments for aggressive and difficult-to-treat cancers. Many viruses naturally target and kill cancer cells, and experimental oncolytic viruses are often engineered to improve that ability.