Targeting the Dark Side of DNA

Neutrolis is developing first-in-class therapies for autoimmune and inflammatory diseases by targeting neutrophil extracellular traps (NETs).

About Us

Candidate Stage Biotech

Neutrolis, Inc. is a biotechnology company developing therapeutics that target neutrophils, the most abundant immune cell in our body.

 

Neutrolis’ lead program targets Neutrophil Extracellular Traps (NETs). NETs are a fundamental arm of the innate immune system and play an important role in chronic and acute diseases.

 

Based in Cambridge, MA, Neutrolis was founded by two of the earliest and most cited leaders in the NETs field and is supported by seasoned business leaders. The company’s pipeline includes NTR-441 and NTR-10 that effectively removes NETs and halt their pathologic effects.

Meet the Founders

Toby Fox, PhD

Chief Executive Officer & Head of Research and Development

Dr. Fox is an immunologist trained at Max Planck Institute and Harvard Medical School. Before co-founding and transitioning into Neutrolis, Toby was a Principal Investigator at University Medical Center Hamburg-Eppendorf. Toby is one of the most cited researchers in the field of NETs with important contributions characterizing the formation and clearance of NETs as well as their implications in vascular diseases and organ injuries.

Abdul Hakkim, PhD

Chairman & Head of Operations

Dr. Hakkim is an immunologist trained at Max Planck Institute and Harvard Medical School. Abdul’s PhD thesis was the first to report on the biology and implications of NETs in autoimmunity. At Harvard, Abdul worked on genetics of innate immunity and co-founded Genma/Artus, a spin-off out of Harvard and now Neutrolis.

Scientific and Medical Advisory Board

Karen H. Costenbader, MD, MPH

Harvard Medical School, Professor of Rheumatology, Immunology and Allergy; Brigham and Women’s Hospital, Director, Lupus program

Karen Costenbader, MD, MPH

Dr. Costenbader is the Director of the Lupus Program at Brigham and Women’s Hospital in Boston and Professor of Medicine at Harvard Medical School. She is also the Chair of the Medical-Scientific Advisory Council for the Lupus Foundation of America. Dr. Costenbader as a key opinion leader for lupus and related autoimmune diseases and advises Neutrolis on clinical trial design and execution.

Mariana J. Kaplan, MD

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Senior Investigator and Chief of Systemic Autoimmunity Branch
Kaplan J. Mariana., MD

Dr. Kaplan is the Senior Investigator and Chief of Systemic Autoimmunity Branch and Acting Director of Lupus Clinical Trial Unit at National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). She is a key opinion leader and her research focuses on identifying abnormalities of the neutrophil subpopulation and the role of NETs in lupus and rheumatoid arthritis and other systemic autoimmune diseases.

Mark R. Looney, MD

University of California San Francisco, Professor of Critical Care and Laboratory Medicine, Attending Physician on the Pulmonary Consult Service and the Intensive Care Units.
Mark Looney, MD
Dr. Looney is a Professor of Critical Care and Laboratory Medicine and Attending Physician on the Pulmonary Consult Service and the Intensive Care Units at University of California San Francisco. Dr. Looney is a key opinion leader in acute lung injury (ALI) / acute respiratory distress syndrome (ARDS), primary graft dysfunction after lung transplantation, and cystic fibrosis.

Joseph A. Madri, MD, PhD

Yale University School of Medicine, Professor of Pathology; Co-Founder Alexion Pharmaceuticals, Inc. (ALXN)

Joseph A. Madri, MD, PhD

Dr. Madri is a Professor of Pathology at Yale University School of Medicine and co-founder of Alexion Pharmaceuticals Inc., a commercial-stage publicly traded ultra-rare orphan disease drug development company. Dr. Madri brings to Neutrolis extensive experience building a preeminent drug discovery and development organization from the earliest stages through launch of multiple commercial products. Dr. Madri also brings a deep understanding of the biological mechanism of inflammation and autoimmune disorders and serves on the editorial boards of numerous scientific journals.

Andreas O. Reiff, MD

Parexel Biotech, SVP and Global Lead, Immunology and Inflammation

Andreas O. Reiff, MD

Dr. Reiff is a senior vice president and the global lead for the Immunology and Inflammation franchise at Parexel, the global clinical research organization. He is an Emeritus Professor of Pediatrics at Children's Hospital Los Angeles, Keck School of Medicine at the University of Southern California and the former Head of the Division of Rheumatology at Children's Hospital Los Angeles. Dr. Reiff received his medical degree from University Medical School in Freiburg, Germany. He completed a research fellowship in the Division of Rheumatology and Bone Marrow Transplantation at Children’s Hospital Los Angeles and a fellowship in pediatric rheumatology at University Children’s Hospital in Freiburg. Dr. Reiff is board-certified in pediatrics and pediatric rheumatology by the European Union and the American Board of Pediatrics. Dr. Reiff assists Neutrolis with clinical development of its therapeutic programs.

Reinhard M. Voll, MD

University of Freiburg, Director of the Department of Rheumatology
Reinhard Voll, MD

Dr. Voll is the Director of the Department of Rheumatology at the University of Freiburg and brings to Neutrolis extensive clinical expertise in autoimmune disorders. Dr. Voll’s research focuses on apoptotic cell death in systemic lupus erythematosus (SLE) and the treatment of antibody-mediated diseases.

Denisa D. Wagner, PhD

Harvard Medical School, Edwin Cohn Professor of Pediatrics: Senior Investigator, Program in Cellular and Molecular Medicine
Denisa Wagner, PhD
Dr. Denisa Wagner is the Edwin Cohn Professor of Pediatrics at Harvard Medical School, member of the Program in Cellular and Molecular Medicine, and the Division of Hematology/Oncology at Boston Children's Hospital. Dr. Wagner is a key opinion leader in the field of NETs and brings deep understanding of vascular biology, adhesion molecules and thrombo-inflammatory pathways to Neutrolis. Her research efforts have uncovered foundational aspects of how pathogenic NETs influence both acute and chronic disorders in humans. These disorders include thrombosis, atherosclerosis, ischemia/reperfusion injury, diabetic wound healing, organ fibrosis, cancer-associated thrombosis, and acute lung injury.

Science

The Dark Side of DNA

DNA is a very long chain of nucleic acids that is wound around histone proteins to form chromatin, which is then packed into the nucleus of eukaryotic cells. Normally, DNA encodes proteins and the instructions needed to make cells function, but it has an additional function within our immune system. Neutrophils, the most abundant immune cells in the body, can expel their long chromatin fibers to form neutrophils extracellular traps (NETs), which activate multiple immune pathways that are implicated in many autoimmune and inflammatory diseases.

Current NETs Management

The balance between NETs formation and clearance is pivotal for maintaining homeostasis. As a result of persistent inflammation, NETs formation overwhelms the natural clearance mechanisms leading to an accumulation of NETs that exacerbates systemic immune response and end-organ damage. To date, NETs treatment strategies have predominantly focused on inhibiting the creation of NETs, a mechanism, which is conserved and highly biologically redundant.

The Chromatinase™ Platform and Lead Program

The Chromatinase™ platform is based on naturally occurring enzymes that degrade that extracellular chromatin that form NETs. The Chromatinase™ platform powers the creation of natural and engineered enzyme analogs that are capable of treating several acute and chronic unmet medical needs and that are optimized for use in therapy. In contrast to existing NETs treatment strategies, NTR-441, the lead application of our Chromatinase™ platform, is an enhanced analog of DNASE1L3, an enzyme produced by immune cells that degrades NETs into biologically inactive fragments to attenuate a severe immune response.

Publications

March 9, 2018

“Neutrophil Extracellular Traps” Inflammation: Fundamental Mechanisms. 2018

March 9, 2017

“Host DNAses prevent vascular occlusion by neutrophil extracellular 
traps,” Science. 2017; 358(6367):1202-1206.

March 9 2011

"Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation” Nature chemical biology. 2011; 7 (2), 75-77

March 9, 2010

“Extracellular DNA traps promote thrombosis,” Proceedings of the National Academy of Sciences. 2010; 107(36):15880-15885.

February 9, 2010

“Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis”, Proceedings of the National Academy of Sciences. 2010; 107 (21), 9813-9818

March 9 2007

“Novel cell death program leads to neutrophil extracellular traps,” Journal of Cell Biology. 2007; 176(2):231-241.

*Note: Dr. Toby Fox publishes under his birth name: Tobias Fuchs

Pipeline

Addressing autoimmune and inflammatory diseases

We are developing disease-modifying therapies for several NET-mediated diseases and significant unmet medical needs.

NTR-441

Systemically active engineered DNASE1L3

NTR-10

Locally active engineered DNASE1L3

Additional Programs

Several therapeutic programs are in development leveraging the robust Chromatinase™ platform

Lupus

Lupus is a systemic autoimmune disease that is characterized by autoantibodies against DNA and inflammation in the joints, skin, kidneys, brain, heart and lungs.

Acute Respiratory Disease Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) occurs when the lungs are severely injured, often by infection or trauma, which causes fluid to leak into the lungs, making it difficult to get oxygen into the bloodstream.

Additional Indications

Neutrolis is developing therapies for additional undisclosed neutrophil-driven conditions.

Indications

Lupus

Lupus is a systemic autoimmune disease that is characterized by autoantibodies against DNA and inflammation in the joints, skin, kidneys, brain, heart and lungs.

Acute respiratory distress syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) occurs when the lungs are severely injured, often by infection or trauma, which causes fluid to leak into the lungs, making it difficult to get oxygen into the bloodstream.

Additional Indications

Neutrolis is developing therapies for additional undisclosed neutrophil-driven conditions.

Contact

Contact Us

Please contact us if you’d like to learn more or if you’re interested in a potential collaboration.

Address

Neutrolis, Inc.

c/o LabCentral

700 Main Street, North

Cambridge, MA 02139

Email

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Site Credit

Neutrophil Scientific Illustrations: Gary Carlson