Immune Finding May Lead to New Ways to Protect People from Rotavirus Infection

Genetic Engineering and Biotechnology News | December 23, 2019

The researchers found that in utero inhibition of molecular signaling in the lymphotoxin (LT) pathway, long known as important in the development of the immune system, prevented a robust antibody response in adult mice to rotavirus, which in humans causes an estimated 215,000 deaths annually, mostly in the developing world. That early disruption limits the ability of the immune system to later trigger and generate production of Immunoglobulin A (IgA) antibodies, the researchers showed. It also interferes with the nature and function of cells in the gut that support the antibody response, called mesenteric lymph node stromal cells.

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MEDICAL

Debiopharm Announces First Patient Dosed in Investigator-initiated, Randomized Phase II, Open-label Clinical Trial for its Antiviral Alisporivir

Debiopharm | January 18, 2021

Debiopharm , a Swiss biopharmaceutical organization, reported the principal patient dosed in a investigator-initiated, randomized phase II, open-label clinical trial for its antiviral alisporivir (Debio 025). The examination will be led by the AP-HP to assess the adequacy and wellbeing of the cyclophilin inhibitor in the therapy of beginning phase, hospitalized COVID-19 patients who don't need clinical ventilation and have not shown indications of intense respiratory distress syndrome. The essential goal of this 'proof-of-concept' preliminary is to assess the decrease in COVID-19 viral burden in alisporivir treated patients. The secondary objective includes the analysis of clinical and radiological efficacy, wellbeing and decency of the compound in addition to Standard of Care (SOC) contrasted with SOC alone. Patients in the investigational arm will get alisporivir either orally or by means of a nasogastric tube, at the portion of 600mg twice every day for 14 days during the preliminary drove by Prof. Jean-Michel Pawlotsky, virologist, Head of the Biology and Pathology Department of the Henri Mondor Hospital Group, Greater Paris University Hospitals. The trial, upheld by both the hospital group gathering and Debiopharm, will be done in numerous centers in France including the Henri Mondor Hospital Group. Medical perceptions have indicated that viral infections , for example, COVID-19 can be life-threatening because of an overcompensation of the body's immune defense system. Part of the cyclophilin inhibitor class of antivirals, this macrocyclic cyclophilin inhibitor could end up being an important extra therapy to SOC because of its non-immunosuppressive nature.

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INDUSTRIAL IMPACT

BioNTech and Medigene Announce Global Collaboration to Advance T Cell Receptor Immunotherapies Against Cancer

BioNTech SE | February 22, 2022

BioNTech SE and Medigene AG a clinical-stage immuno-oncology company focusing on the development of T cell immunotherapies, announced that they have entered a multi-target research collaboration to develop T cell receptor (TCR) based immunotherapies against cancer. The initial term of the collaboration is three years. Medigene will contribute its proprietary TCR discovery platform for the development of TCRs against multiple solid tumor targets nominated by BioNTech. Medigene’s automated, high throughput TCR discovery platform is designed to bypass central tolerance to yield high affinity TCRs. T cell therapy has become a disruptive medical innovation in the treatment of patients with cancer. Engineered TCR-modified T cells (TCR-T cells) are reprogrammed to express a TCR that can recognize specific antigens only present on tumor cells, thereby enabling a precise and potent immune response to attack a patient’s tumor. “This collaboration with Medigene expands our cell therapy portfolio and TCR discovery capabilities, and further strengthens our ability to be a leader in the rapidly emerging field of engineered cell therapies. We look forward to working closely with Medigene to develop new treatments which address solid tumors with high unmet medical need.” Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: “Medigene is at the forefront of the development of TCR-T therapies for oncology. The sale and licensing deal with BioNTech is an important validation from a global leading biotech company of our proprietary technologies to discover and characterize highly specific TCRs and empower resulting TCR-T cells to fight solid tumors. This partnership provides Medigene with meaningful financial resources to fuel our next generation development programs targeting potentially novel tumor-specific “dark matter” antigens, further tools to enhance T-cell-based immunotherapies, as well as additional potential strategic deals with future milestone payments and royalties.” BioNTech will acquire Medigene’s next generation preclinical TCR program, which combines TCR-4 of Medigene’s MDG10XX program targeting PRAME with Medigene’s proprietary PD1-41BB switch receptor technology. BioNTech will also obtain the exclusive option to acquire additional existing TCRs in Medigene’s discovery pipeline and will receive licenses to the company’s PD1-41BB switch receptor and precision pairing library. This has the potential to augment TCR cell therapy efficacy and can be applied to all BioNTech cell therapy programs. Under the terms of the agreement, Medigene will receive EUR 26 million upfront, as well as research funding for the period of the collaboration. BioNTech will be responsible for global development and hold exclusive worldwide commercialization rights on all TCR therapies resulting from this research collaboration. Medigene will be eligible to receive development, regulatory and commercial milestone payments up to a triple digit million EUR amount per program in addition to tiered deferred option payments on global net sales for products based on TCRs arising from the collaboration and royalties on products utilizing at least one of the licensed technologies. About BioNTech Biopharmaceutical New Technologies is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bi-specific checkpoint immuno-modulators, targeted cancer antibodies and small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Genmab, Sanofi, Bayer Animal Health, Genentech, a member of the Roche Group, Regeneron, Genevant, Fosun Pharma and Pfizer. About Medigene Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard) is a publicly listed biotechnology company headquartered in Planegg/Martinsried near Munich, Germany. With its scientific expertise, Medigene is working on the development of innovative immunotherapies to enhance T cell activity against solid cancers in fields of high unmet medical need. Medigene’s pipeline includes preclinical as well as clinical programs in development. Medigene’s strategy is to develop its own therapies towards clinical proof-of-concept. In addition, the Company offers selected partners the opportunity to discover and develop therapies on the basis of its proprietary technology platforms. In return for such partnerships, Medigene expects to receive upfront and milestone payments as well as research and development funding and royalties on future product sales. About Medigene’s TCR-T cells T cells are at the center of Medigene’s therapeutic approaches. With the aid of Medigene’s immunotherapies the patient’s own defense mechanisms are activated, and T cells harnessed in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs). The resulting TCR-T cells should thereby be able to detect and efficiently kill cancer cells. About Medigene’s PD1-41BB switch receptor Checkpoint inhibition via PD1-PDL1 pathway: Solid tumor cells are known to be sensitive to killing by activated T cells. Tumor cells can escape this killing activity by expressing inhibitory molecules, so-called ‘checkpoint proteins’, such as Programmed Death Ligand 1 (PD-L1) on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 by tumors represents an adaptive immune resistance mechanism that can lead to tumor survival and growth. About Medigene’s precision pairing library T cell receptors (TCRs) consist of an alpha and a beta chain, which together act as a receptor on the cell surface of T cells. Medigene's therapies aim to equip the patient's own T cells with tumor-specific TCRs. The resulting TCR-T cells should thereby be able to detect and efficiently kill cancer cells. The precision pairing library allows selection of specific modifications in each chain of a TCR so that the alpha and beta chains preferentially pair with each other, with the result that improved TCR surface expression and/or functionality is achieved.

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MEDICAL

TGen Selects MemVerge to Accelerate Idiopathic Pulmonary Fibrosis Research Discovery with Big Memory Technology

MemVerge | March 21, 2022

MemVerge™, the pioneers of Big Memory software, today announced that TGen, the Translational Genomics Research Institute, an affiliate of City of Hope, has selected MemVerge Memory Machine Big Memory virtualization software to accelerate time to discovery for Idiopathic Pulmonary Fibrosis (IPF), a disease which affects 100,000 people annually in the U.S. Using MemVerge technology, TGen is able to dramatically speed analytical processing by nearly 36% for single-cell RNA sequencing. As a nonprofit medical research institute, TGen researchers process single-cell RNA sequences to characterize cell transcriptomic profiles. The process can take up to six and a half hours to analyze a matrix of 30,000 genes by 114,000 cells. With consistently growing datasets, this processing time was preventing a desired time to discovery. The data required for analysis was simply too large to retain in traditional memory, and scaling capacity with dynamic random-access memory (DRAM) was too costly. TGen has instead deployed memory virtualization technology from MemVerge which virtualizes both DRAM and PMem (persistent memory) memory technologies, to increase the memory pool available for processing without requiring more high-cost DRAM. The solution further speeds TGen's genomics sequencing analysis with Memory Machine ZeroIO in-memory snapshots which capture multi-terabyte data sets at any point for rapid reloads at each stage of processing. The ZeroIO snapshot service is 1,000 times faster than the fastest storage snapshot to SSD and enables TGen to run processing workflows in parallel. This ensures that in the event of a system crash, in-memory snapshots are available to instantly re-start long running jobs without lengthy reloading. By utilizing the snapshotting and cloning capabilities of Memory Machine, we were able to parallelize the processing workflow, As a result, we can now save nearly 36% of computational time while also taking advantage of the big memory nodes. This will save a lot of time in downstream analysis." Glen Otero, Ph.D., Vice President of Scientific Computing at TGen. MemVerge Memory Machine has quickly resulted in research value for TGen, We have removed performance barriers from their research process so that they are able to perform vital, life-saving, research faster than ever possible. Now TGen is expanding the use of Big Memory technology across other research use cases where results and discoveries can produce findings for a healthier tomorrow." Jonathan Jiang, COO of MemVerge. MemVerge Memory Machine makes 100% use of available memory capacity while providing new operational capabilities to memory-centric workloads. Memory Machine answers the need for a modern in-memory computing model to support emerging applications that require real-time analytics, true in-memory computing, and fault-tolerant memory persistence to speed massive processing workloads. About MemVerge MemVerge is pioneering Big Memory Computing and Big Memory Cloud technology for the memory-centric and multi-cloud future. MemVerge® Memory Machine™ is the industry's first software to virtualize memory hardware for fine-grained provisioning of capacity, performance, availability, and mobility. On top of the transparent memory service, Memory Machine provides another industry first, ZeroIO™ in-memory snapshots which can encapsulate terabytes of application state within seconds and enable data management at the speed of memory. The breakthrough capabilities of Big Memory Computing and Big Memory Cloud Technology are opening the door to cloud agility and flexibility for thousands of Big Memory applications.

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