GARFIELD classifies disease-relevant changes in the genome

Medical Xpress | January 30, 2019

Researchers at the Wellcome Sanger Institute and EMBL's European Bioinformatics Institute (EMBL-EBI) have developed a new approach to understanding the functional effects of genetic variations associated with a disease, even if they aren't located in a gene. Using this approach could help scientists uncover previously unknown mechanisms that control gene activity and determine whether cell work normally or, in the case of genetic diseases, the cells malfunction. This knowledge will help drive new research and could identify new targets for drug development.
The tool, called GARFIELD, uses a computational approach known as functional enrichment. This approach combines the positions on the genome of disease-associated DNA changes with information on the role of those regions. In this way, the system highlights those variations that are known to produce changes in the activity of genes that are relevant to the disease being studied. GARFIELD has been designed to take into account the major factors that could confuse the results of a study and can include weak disease associations to increase its power for insight. Because of these measures, the system provides the widest information on the largest number of disease associations.

Spotlight

Andrea Zobel, Global Senior Director Clinical Project Management at Parexel International talks to Pharma IQ about the power of the Internet of Things (IOT) in clinical trial supply.

Spotlight

Andrea Zobel, Global Senior Director Clinical Project Management at Parexel International talks to Pharma IQ about the power of the Internet of Things (IOT) in clinical trial supply.

Related News

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.

Read More

AI

Iktos Partners with Kadmon to Use AI for New Drug Design

Iktos, Kadmon | May 19, 2021

Iktos, a company specializing in Artificial Intelligence for new drug design, announced today that it has signed a Research Collaboration Agreement with Kadmon, a clinical-stage biopharmaceutical company based in New York, USA, under which Iktos' generative modeling artificial intelligence (AI) technology will be used to allow the rapid and cost-effective design of novel drug candidates. Iktos will use its de novo structure-based generative modeling technologies to find novel compounds that meet a pre-defined target product profile as part of the deal, to speed up Kadmon's early-stage discovery efforts. Kadmon discovers, develops, and delivers small molecules and biologics for the treatment of human diseases. Intending to identify and develop new product candidates for significant unmet medical needs, Kadmon is expanding and incorporating novel drug discovery platforms. The AI technology developed by Iktos, which is focused on deep generative models, aids in the speed and efficiency of the drug discovery process. Iktos' technology creates virtual novel molecules that have all of the properties of a successful drug molecule automatically. This approach, which has been validated by Iktos' other collaborations, is an innovative approach to one of the most difficult problems in drug design: finding molecules that meet several important drug criteria at the same time, such as potency, selectivity, safety, and project-specific properties. Iktos' technology enables the creation of new hits with optimal protein-ligand interactions in early-stage discovery projects, as predicted by molecular modeling technology. This technique allows for a one-of-a-kind discovery of chemical space, as well as the development of innovative molecule designs with greater Freedom to Operate. Furthermore, allowing multi-parametric in silico optimization from the start of a project greatly reduces the hit finding and hit-to-lead optimization phases. About Iktos Iktos, a French start-up founded in October 2016, specializes in the development of artificial intelligence technologies for chemical research, especially medicinal chemistry, and new drug design. Iktos is working on a proprietary and innovative approach focused on deep learning generative models that allow users to build molecules in silico that follow all of the performance criteria of a small molecule discovery project using existing evidence. Iktos technology allows for significant efficiency gains in upstream pharmaceutical R&D. Iktos' software is utilized as both professional services and a SaaS software platform, Makya. Spaya, a synthesis planning software built on Iktos' proprietary AI technology for retrosynthesis, is also in the works.

Read More

LifeMine Therapeutics and GSK Enter Drug Discovery and Development Alliance

LifeMine | March 28, 2022

LifeMine Therapeutics Inc., a biopharmaceutical company reinventing drug discovery by mining genetically-encoded small molecules (GEMs) from the biosphere, today announced a strategic R&D collaboration with GlaxoSmithKline (GSK). The collaboration will provide GSK with access to LifeMine’s genomically enabled drug discovery platform to identify novel small molecule leads directed to up to three human targets provided by GSK addressing multiple disease areas. Under the terms of the collaboration, LifeMine will receive an upfront payment of $70 million that includes both cash and an equity investment by GSK in LifeMine in its Series C round of financing. In addition, LifeMine is eligible to receive undisclosed discovery, development and commercial milestone payments for each collaboration product. LifeMine will be also eligible to receive royalties on net sales of any drug from the collaboration that is commercialized by GSK. LifeMine and GSK will collaborate closely on the discovery process, with each company leveraging its core capabilities and equally sharing costs to IND filing. GSK will be responsible for all development and commercialization. This is a transformative collaboration for LifeMine, and marks the first such agreement in genomic drug discovery from fungi, nature’s virtuoso medicinal chemists, We are thrilled to partner with GSK to expand the potential of our drug discovery engine while we continue to advance our own lead programs. We look forward to a productive partnership which we are confident will result in novel therapeutic options for patients.” Gregory Verdine, Ph.D., co-founder, chief executive officer and chief scientific officer of LifeMine. LifeMine aims to bring unparalleled speed, predictability and scalability to small-molecule drug discovery, offering the potential to rapidly advance multiple high-impact precision medicines to solve intractable disease challenges, irrespective of therapeutic area. LifeMine’s Avatar-Rx platform seamlessly integrates high-throughput microbiology, data science and machine learning, genome engineering and automation technologies to search the fungal biosphere for novel GEMs having a predetermined target and biological function. Downstream of GEM discovery, LifeMine’s platform further integrates chemoinformatic-assisted drug optimization and state-of-the art chemical synthesis with biotransformation to advance new product candidates into development. GSK’s drug discovery approach focuses on advanced technologies, including human genetics, functional genomics and machine learning to increase our probability of success, This approach leads to genetically validated targets that are twice as likely to succeed as medicines, but due to their novelty often require innovation to unlock their potential. We are looking forward to teaming up with LifeMine to use their cutting-edge platform, so together we can identify what nature might have already created as chemistry starting points to increase our chances of developing transformational new drugs for patients.” John Lepore, SVP, Head of Research, GSK. About LifeMine Therapeutics LifeMine Therapeutics is reinventing drug discovery by mining genetically-encoded small molecules (GEMs) from the biosphere. Through its proprietary, evolutionarily-derived genomic drug discovery platform, LifeMine aims to bring unparalleled speed, predictability and scalability to small molecule drug discovery. LifeMine has discovered, in genomic space, hundreds of potentially high-impact drug candidates relevant to targets across all major disease areas, and has an initial focus on advancing highly impactful precision medicines in oncology and immune modulation. The Company was founded in 2017 by renowned entrepreneur/scientists Gregory Verdine, Ph.D., and Richard Klausner, M.D., and entrepreneur/company-builder WeiQing Zhou. Headquartered in Cambridge, Mass., and with a second site at Gloucester Harbor, Mass., LifeMine has raised more than $295 million from leading life science investors.

Read More