Torque is developing a new class of Deep-Primed™ immune cell therapeutics for the treatment of cancer. We are using a technology platform to anchor powerful biotherapeutics—stimulatory cytokines, antibodies, and small molecules—directly to immune cells to direct and evoke immune cell responses, locally in the tumor microenvironment. We have completed preclinical studies with our initial clinical candidate—Deep IL-15—demonstrating increased t-cell proliferation, engraftment, and tumor cell killing, including the potential to improve on pre-conditioning regimens, and we will be initiating the first clinical trials in 1H 2018.
Torque is applying the Deep-Priming™ platform across all immune cell therapeutic types: CART, TCR, NK cells, and Tumor-Activated Antigen (TAA)-specific T cells. In hematologic cancers, our technology has the potential to improve on the initial success of CART immune cell therapeutics, enabling more durable responses and with less toxicity. For solid tumors, Deep-Priming has the potential to enable efficacy against cancers that are protected by hostile microenvironments not readily addressable with the first generation of immune cell therapies.
Deep-Priming™ Technology Platform
Immune cell therapeutics targeting tumors—specifically, CAR-T, TCR, and targeted T cells—confront a host of immunosuppressive signals coming from the tumor microenvironment. The tumor protects itself from immune system attack by co-opting these mechanisms that the immune system normally uses to turn itself off at the end of a successful immune response.
Torque is developing approaches to overcome these barriers to effective and durable cancer immunotherapy. Our Deep-Priming platform is based on more than 10 years of research and development focused on taking very potent immunomodulatory drugs—cytokines, antibodies, and small molecules—that have the ability to activate and protect T cells from this “hostile” tumor microenvironment. Administering these immunomodulators systemically to a patient can cause lethal toxicity, activating immune cells throughout the body. Instead, we want to activate only the T cells that are going after the tumor, and we do this by anchoring the immunomodulators to the surface of the immune cell to act locally, in the microenvironment.
We call these anchored drugs “backpacks,” which we engineer to either act on the carrier cell itself (this is known as an autocrine signaling loop), so the drug is released at the cell surface and binds to the cell’s own receptors; or they are engineered to deliver a drug that activates other immune cells in the microenvironment (this is known as a paracrine signaling loop) to boost the immune response by recruiting other immune cells for a durable, long-lasting anti-tumor efficacy.
Deep-Priming involves two key steps:
Polymerize the immumodulator drugs with copies of themselves to form the backpack that is made out of the drug, connected with a reversible cross-linker
Chemically link the backpack to the carrier T cell, anchoring it to proteins on the T cell surface.
We design the anchor and cross-linkers to respond to the biology of the cell when it finds the tumor, to ensure local release in the tumor microenvironment. Activation of the T cell at the tumor site triggers upregulation of an enzyme on the cell surface, and this chemical reaction dissolves the backpack cross-linkers, releasing the protein so it can bind to the cell surface receptors. This process supercharges the immune cell to attack the tumor. In this way, the T cell releases the drug when it sees its cancer target.
Deep-Primed™ immune cell therapeutics incorporate powerful biotherapeutics that enable precise control of dose, timing, and location of immune cell function, supercharging them to:
Activate the immune cells that are targeting the tumor deep within the tumor microenvironment (avoiding continuous, systemic exposure that acts on all cells and can cause lethal toxicity)
Allow those immune cells to overcome immune-suppressive mechanisms in the the tumor microenvironment that prohibit the immune cells from recognizing and attacking the tumor
Rapidly engraft and proliferate in the tumor
Activate those immune cells to increase tumor cell destruction
Persist in the body to provide durable protection
Deep-Primed T cells retain all the natural functions of natural T cells in vivo, including trafficking to tissues, recognizing tumors, and destroying tumor cells.
Deep-Primed T Cells on the move:
This video shows Deep-Primed T Cell migrating through a collagen matrix in cell culture. The blue flashlights visible on the tail of each cell are clustered immunomodulators carried by the T cell surface receptors. The backpacks have been moved to the rear of the cell because that’s where the T cell carries those receptors.
A Deep-Primed T cell recognizes and infiltrates its target:
When the Deep-Primed T cell encounters a tumor cell (green), the backpack on its cell surface (blue) starts moving into the interface. The blue speckles show the early stages of the T cell moving the cluster of backpacked immunomodulators into the interface with the tumor cell, where the drug cross-linkers can dissolve and release the drug in a controlled and measured process.
Ulrik is a co-founder and CEO of Torque. He was previously a founder of Merrimack (NASDAQ:MACK) where he served as the Chief Scientific Officer until 2015 and remains on the board of directors. At Merrimack, Ulrik was responsible for R&D and the early phases of clinical development. He also served as Chief Executive Officer of Silver Creek Pharmaceuticals, Inc., a majority-owned subsidiary of Merrimack, from July 2010 to March 2014. Ulrik holds a PhD in molecular biology from the University of Copenhagen and did research at UCSF and MIT.
Bart Henderson, MBA
Bart is a co-founder and President of Torque. He was previously President and Founder of Rhythm and its subsidiary, Motus (acquired by Allergan), with responsibility for business development, finance, marketing, and manufacturing operations. Prior to that, he was Entrepreneur-in-Residence at MPM Capital , Chief Business Officer of Radius where he was a founding employee, head of sales and marketing at Vertex, head of business development at Microbia (now Ironwood Pharmaceuticals Inc.), and also held marketing management positions at Amgen and Merck. He received an MBA from Dartmouth’s Tuck School of Business and a BA from Amherst College.
Thomas Lars Andresen, PhD
Thomas is a co-founder and leads discovery at Torque. Since 2007 he has been a Professor and group leader of the Colloids and Biological Interfaces group at DTU Nanotech, and was head of the DTU Center for Nanomedicine and Theranostics. Thomas is an expert in biomaterial engineering and drug delivery. Thomas founded NANOVI in 2011 and was formerly Head of R&D at LiPlasome Pharma. Thomas has a strong experience in the fields of organic chemistry, biophysics, nanotechnology and nanomedicine, drug delivery and cancer biology, and holds a track record of more than 100 research or review articles and multiple patent applications.
Becker Hewes, MD
Becker is the Chief Medical Officer of Torque. He has over 10 years industry experience, most recently serving as an Executive Medical Director at Novartis Institute for Biomedical Research. He was responsible for a wide array of clinical and preclinical immuno-oncology compounds as well as the early clinical development of ribociclib in breast cancer. He has held positions within early oncology clinical development at both Genzyme and AstraZeneca. At Wyeth Oncology, Becker was responsible for the supplemental NDA filing for Torisel in Mantle Cell Lymphoma as well as the phase 1-3 program for bosutinib resulting in FDA approval in chronic myeloid leukemia. Prior to joining industry, his research focused on preclinical models of anti-tumor immunity at the Emory-Yerkes Vaccine Center.
Doug Cole, MD, has served as a member of our board of directors since August 2015. He has been a general partner of Flagship Ventures, where he has focused on life science investments, since 2001. At Flagship, Dr. Cole has led investments in Agios Pharmaceuticals (NASDAQ:AGIO), Alvine Pharmaceuticals, Avedro, CombinatoRx (NASDAQ:ZLCS), Concert Pharmaceuticals (NASDAQ:CNCE), Editas (NASDAQ:EDIT), Quanterix , Receptos (NASDAQ:RCPT), Seventh Sense Biosystems, and Tetraphase Pharmaceuticals (NASDAQ:TTPH). He co-founded Flagship portfolio companies Ensemble Therapeutics, Permeon Biologics, Moderna Therapeutics, and Syros Pharmaceuticals. He currently serves on the Boards of Directors of Agios, Denali, Editas, Ensemble, KSQ, and Quanterix and formerly served on the Board of Directors of Avedro, AVEO Pharmaceuticals (NASDAQ: AVEO), CombinatoRx, Concert, CGI, Moderna, Morphotek, Permeon, Receptos, Resolvyx, Selecta, Seventh Sense, Syros, and Tetraphase. Dr. Cole holds a B.A. in English from Dartmouth College and an MD from the University of Pennsylvania School of Medicine.
John M. Dineen
John M. Dineen has served as a member of our board of directors since January 2016. John is an Operating Advisor to Clayton, Dublier & Rice, LLC, a private equity firm based in New York. John serves as the Chairman of Healogics Corp and on the Board of Merrimack (NASDAQ:MACK). From 1986 to 2015, Mr. Dineen served in a variety of leadership roles in the US, Europe and Asia with the GE Company. During his tenure at GE he served as President and Chief Executive Officer of GE Healthcare, Chief Executive Officer of GE Transportation, President of GE Plastics, General Manager of GE’s Power Equipment business and General Manager of GE Appliance’s, Microwave and Air-Conditioning businesses. John holds BS degrees in Biology and Computer Science from the University of Vermont.
Doug Lauffenburger, PhD
Doug Lauffenburger, PhD, has served as a member of our board of directors since January 2016. Doug is the head of the Department of Biological Engineering at the Massachusetts Institute of Technology and a pioneer in applying engineering principles to biological research. His expertise spans multiple disciplines including chemical engineering, bioengineering, biotechnology process engineering, biophysics, quantitative cell and structural biology, systems biology, and applied mathematics. He has filed numerous patents, authored a key textbook on receptor biology, and published more than 200 peer-reviewed articles. He is a member of the National Academy of Engineering, and has served on numerous bio/pharma industry scientific advisory boards including for Pfizer, Astra-Zeneca, Eli Lilly, Johnson & Johnson, and Merrimack. Doug received his BS in Chemical Engineering from the University of Illinois and his PhD in Chemical Engineering from the University of Minnesota
Bart Henderson, MBA
Bart Henderson, MBA, is a co-founder and President of Torque and has served as a member of our board of directors since July 2017. He was previously President and Founder of Rhythm and its subsidiary, Motus (acquired by Allergan), with responsibility for business development, finance, marketing, and manufacturing operations. Prior to that, he was Entrepreneur-in-Residence at MPM Capital , Chief Business Officer of Radius where he was a founding employee, head of sales and marketing at Vertex, head of business development at Microbia (now Ironwood Pharmaceuticals Inc.), and also held marketing management positions at Amgen and Merck. He received an MBA from Dartmouth’s Tuck School of Business and a BA from Amherst College.
Ulrik B. Nielsen, PhD
Ulrik Nielsen, PhD, is a co-founder and CEO of Torque and has served as a member of our board of directors since August 2015. He was previously a founder of Merrimack (NASDAQ:MACK) where he served as the Chief Scientific Officer until 2015 and remains on the board of directors. At Merrimack, Ulrik was responsible for R&D and the early phases of clinical development. He also served as Chief Executive Officer of Silver Creek Pharmaceuticals, Inc., a majority-owned subsidiary of Merrimack, from July 2010 to March 2014. Ulrik holds a PhD in molecular biology from the University of Copenhagen and did research at UCSF and MIT.
Darrell Irvine, PhD, is a co-founder of Torque and Chairman of our SAB. Darrell is a Professor at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. He also serves on the steering committee of the Ragon Institute of MGH, MIT, and Harvard. His research is focused on the application of engineering tools to problems in cellular immunology and the development of new materials for vaccine and drug delivery. Current efforts are focused on problems related to vaccine development for HIV and immunotherapy of cancer. This terdisciplinary work has been recognized in numerous awards, including a Beckman Young Investigator award, an NSF CAREER award, selection for Technology Review’s ‘TR35’, election as a Fellow of the Biomedical Engineering Society and the American Institute for Medical and Biological Engineering. He is the author of over 70 publications, reviews, and book chapters and an inventor on numerous patents. Darrell holds a Bachelor’s Degree in Engineering Physics from University of Pittsburgh and a PhD from MIT in Polymer Science.
Ulrik B. Nielsen, PhD
Ulrik Nielsen, PhD, is a co-founder and CEO of Torque. He was previously a founder of Merrimack (NASDAQ:MACK) where he served as the Chief Scientific Officer until 2015 and remains on the board of directors. At Merrimack, Ulrik was responsible for R&D and the early phases of clinical development. He also served as Chief Executive Officer of Silver Creek Pharmaceuticals, Inc., a majority-owned subsidiary of Merrimack, from July 2010 to March 2014. Ulrik holds a PhD in molecular biology from the University of Copenhagen and did research at UCSF and MIT.
Catherine M. Bollard, MD, MBChB
Catherine M. Bollard, MD, MBChB, is Professor of Pediatrics and Immunology at The George Washington University and the Chief of the Division of Allergy and Immunology at Children’s National, Washington DC. She is a distinguished hematologist and immunotherapist, a member of the Division of the Blood and Marrow Transplantation, and the Principal Investigator and Co-Director of the Immunology Initiative of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System. Prior to Children’s National, she was at the Baylor College of Medicine, where she was a tenured Professor in the Department of Pediatrics. Prior to that, she served as a Postdoctoral Fellow at Texas Children’s Hospital. Dr. Bollard received her medical degree from Otago University Medical School in New Zealand.
Malcolm Brenner, MD, PhD
Malcolm Brenner, MD, PhD, is Founding Director of the Center for Cell and Gene Therapy at Baylor College of Medicine (BCM), Texas Children’s Hospital and The Methodist Hospital. He is a Distinguished Service professor, in the Departments of Pediatrics and of Medicine at BCM. Malcolm’s clinical research interests span many aspects of stem cell transplantation, using genetic manipulation of cultured cells to obtain therapeutic effects. Efforts in Malcolm’s laboratory to analyze the cell of origin when relapse occurs in patients with acute myelogenous leukemia led Malcolm’s team to be the first to label autologous bone marrow cells genetically after purging, prior to being reintroduced to the patient. His group recently pioneered the first clinical use of a new safety switch for cellular therapy. He has won many awards for his work and in 2011 these including the ASGCT Outstanding Achievement Award and the American Society of Hematology Mentor Award. Malcolm received his medical degree and subsequent PhD from Cambridge University, England.
Dane Wittrup, PhD
Dane Wittrup, PhD, is the C.P. Dubbs Professor of Chemical Engineering and Biological Engineering at MIT and Associate Director of MIT’s Koch Institute. In 2012, he was elected to the National Academy of Engineering. He was also elected a Fellow of the American Association for the Advancement of Science in 2011. Dane is co-founder and acting Chief Scientific Officer at Adimab and is a fellow of the American Institute of Biomedical Engineers. He has also served as the J. W. Westwater Professor of Chemical Engineering, Biophysics, and Bioengineering at the University of Illinois at Urbana-Champaign. He previously worked as a postdoctoral research associate in Amgen’s Yeast Molecular Biology Group. Dane holds a PhD and MS in Chemical Engineering from the California Institute of Technology and a BS in Chemical Engineering from the University of New Mexico.
Cassian Yee, MD
Cassian Yee, MD, is Clinical Oncologist and Professor in the Departments of Melanoma Medical Oncology and Immunology, Director of Solid Tumor Cell Therapy, and Co-Director of the Adoptive Cellular Therapy Platform at MD Anderson Cancer Center. Dr. Yee’s research over the last 20 years has been focused on developing immune-based therapies for the treatment of patients with cancer. His specialty, in the area of adoptive cellular therapy, involves the isolation of rare tumor antigen-specific T cells from the peripheral blood, manipulation of immune modulating factors to enhance their effector function and in vivo persistence, and expansion to numbers sufficient for adoptive transfer. He is an elected member of the American Society of Clinical Investigators, recipient of Clinical Translational Scientist Award from Burroughs Wellcome Fund, CPRIT Clinical Investigator award, and co-Leader of the Stand Up to Cancer—American Association for Cancer Research / Cancer Research Institute Immunotherapy Dream Team. Dr. Yee completed his medical degree in Canada followed by an internal medicine residency at Stanford before going on to an oncology fellowship at the University of Washington. He ascended to the position of Professor at the University of Washington and Full Member at the Fred Hutchinson Cancer Research Center.
Peter Zandstra, PhD
Peter Zandstra, PhD, is a Professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering and at the Donnelly Centre for Cellular and Biomolecular Research. Peter is also a Professor at the University of British Colombia (UBC) in the Departments of Medical Genetics and Chemical Engineering and Biological Engineering. He graduated with a Bachelor of Chemical Engineering degree from McGill University, obtained his PhD from UBC in Chemical Engineering and Biotechnology, and continued his research training as a Postdoctoral Fellow in Biological Engineering at the Massachusetts Institute of Technology. Research in the Zandstra Laboratory is focused on the generation of functional cells and tissues from adult and pluripotent stem cells. Peter is the Canada Research Chair in Stem Cell Bioengineering and is a recipient of a number of awards, including the John Simon Guggenheim Memorial Foundation Fellowship and the Till and McCulloch Award. He is a Fellow of the American Association for the Advancement of Science and of the Royal Society of Canada (Science). In addition to his academic roles, Peter is the Chief Scientific Officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and Chief Technology Officer at ExCellThera, a clinical-stage company focusing on the development of stem cell-based therapies for leukemia and other blood diseases.
TORQUE believes that working in multidisciplinary teams is essential to innovation.
We have diverse backgrounds in immunology, protein engineering, nanoparticle engineering, computational biology, drug development and medicine (to name a few). We are always looking for talented individuals with entrepreneurial spirits.
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