Developing novel therapies for the treatment of fibrosis and fibroproliferative diseases

About MDI

MDI Therapeutics is a pharmaceutical company developing novel therapies for the treatment of fibrosis and fibroproliferative diseases. The Company was founded on key enabling technologies developed at the University of Michigan. MDI’s lead program is a first-in-class orally available plasminogen activator inhibitor (PAI-1) inhibitor.

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The Science

PAI-1: Multi-Functional, Metastable Protein with Unique Mechanism

Attractive pharmaceutical target, yet no approved drugs known to directly inhibit PAI-1

  • Initially identified in the 1980s
    • Best understood for its role regulating fibrinolysis and physiologic wound healing by rapid inhibition of tPA and uPA
    • Implicated in numerous pathological processes, including CVD, arterial and venous thrombosis, and chronic fibrotic diseases
  • 100s of small-molecules, natural products, and mAb antagonists/inhibitors have been described
  • Inherent structural instability of PAI-1 biases HTS “hits” toward promiscuous molecules with low affinity, hydrophobicity, and poor specificity

References: Thromb Haemost. 2008 Dec;100(6):1029-36. | Front Med (Lausanne). 2019; 6: 25. | Proc Natl Acad Sci USA. 2014 Oct 28;111(43):15414-9. | Expert Opin Ther Pat. 2013;23:801-15. | Eur J Med Chem. 2015;92:619-36. | Methods in Enzymology. 501:177-207, 2011.

Mechanism of Action

Physiologic PAI-1 Regulates Wound Healing

Pathologic PAI-1 promotes pro-inflammatory, pro-fibrotic and pro-thrombotic processes

Direct correlation between PAI-1 and the severity of fibrosis has been substantiated in vivo in multiple models by many different investigators

PAI-1 has been shown to be a critical down-stream mediator of master pro-fibrotic regulators including TGF-β and matrix stiffness, both of which upregulate PAI-1 expression

mechanism of action supporting image mechanism of action supporting image

Figure adapted from: J Clin Invest. 2007;117(3):524-529.

Our Team

  • Stephen Benoit Profile Picture

    Stephen Benoit

    President & CEO

    Stephen Benoit

    President & CEO

    Stephen Benoit has served as a member of MDI’s board of directors since November 2017. He brings broad experience in VC-backed start-ups, and small and large-cap public companies in the pharmaceuticals, food & agriculture biotechnology, food safety training and education, consumer packaged foods, and specialty ingredients industries. Since 2012, Mr. Benoit has served as a member of the board of directors of Metabolic Solutions Development Company (MSDC), a clinical-stage developer of small molecule therapeutics to treat diseases associated with metabolic dysfunction, including diabetes, NASH, Alzheimer’s disease, and Parkinson's disease, and was MSDC’s chief executive officer from October 2010 to 2017. Prior to joining MSDC, Mr. Benoit was the founding President & COO of the International Food Protection Training Institute, which was designated by U.S. Food and Drug Administration as the National Coordination Center for Food Safety Training; and from September 2001 through 2008, he was a co-founder, President & CEO of NanoMed Pharmaceuticals, a developer of nanoparticle-formulated therapeutic agents to treat cancer. Mr. Benoit has also held senior management positions with a developer of direct-to-consumer personal genetic assessments, a Fortune 250 global food manufacturing company, a small-cap public company that developed and manufactured antimicrobial peptides for food and animal health products, and a small-cap public company that pioneered food & agricultural biotechnology. He began his career at Bank of America.

    Mr. Benoit earned a Master of Business Administration, Finance and a Bachelor of Business Administration, Finance from Loyola Marymount University (Los Angeles). He has been a Visiting Executive Lecturer at the University of Virginia, Darden School of Business and Western Michigan University.

  • Daniel A. Lawrence Profile Picture

    Daniel A. Lawrence, PhD

    Founder/Chairman, Clinical & Scientific Advisory Board

    Daniel A. Lawrence, PhD

    Founder/Chairman, Clinical & Scientific Advisory Board

    Daniel A. Lawrence is Professor of Cardiovascular Medicine, and the Frederick G L Huetwell Professor of Basic Research in Cardiovascular Medicine at the University of Michigan. He is a recognized world leader in serpin biology. He has published over 140 peer-reviewed articles, holds numerous patents in the field, and was awarded the prestigious 2010 International Society for Fibrinolysis and Proteolysis Prize. He has served as the Chair of the Plasminogen Activation & Extracellular Proteolysis Gordon Conference, and Co-Chair of the Xth International Workshop on Molecular & Cellular Biology of Plasminogen Activation.

    Dr. Lawrence’s scientific career has focused on the impact of serpins in the pathology of vascular function and disease, where he has made significant discoveries. Dr. Lawrence was a member of the team that cloned and purified plasminogen activator inhibitor-1 (PAI-1), allowing its recognition as a member of the serpin family of structurally related proteins that inactivated proteases via a then unknown mechanism. He proceeded to study the serpin mechanism of action and was the first to propose the now recognized serpin mechanism of inhibition through distortion of the protease catalytic site. Dr. Lawrence has pioneered research in advancing an understanding of how the unique molecular structure of serpins contributes to diseases as diverse as inflammation, fibrosis, and thrombosis, including being the first to identify a novel serpin target site that could potentially be exploited to pharmacologically regulate a variety of family members and functions.

    Dr. Lawrence received his Ph.D. in Molecular Biology from Umeå University, Umeå Sweden and completed his postdoctoral training at the University of Michigan. He was then appointed Research Investigator in the Department of Internal Medicine at the University of Michigan in 1992. In 1995, Dr. Lawrence moved to the American Red Cross Holland Laboratory for Biomedical Sciences where he was appointed Scientist I (Assistant Professor) in the Department of Biochemistry and served a concurrent appointment as Adjunct Assistant Professor in the Department of Biochemistry and Molecular Biology at George Washington University in Washington DC. He joined the University of Maryland School of Medicine in 2004 as Professor in the Department of Surgery and in 2005 returned to the University of Michigan as Professor of Cardiovascular Medicine.

    A list of Dr. Lawrence’s publications can be found here.

  • J. Craig Hartman Profile Picture

    J. Craig Hartman, PhD

    Vice President, Preclinical Development

    J. Craig Hartman, PhD

    Vice President, Preclinical Development

    Craig Hartman brings to MDI over 35 years of experience working in Non-Clinical Pharmacology and Toxicology, successful Preclinical and Clinical Drug Development, Regulatory and Medical Writing, Strategic Planning and Due Diligence, Synthetic Small Molecules and Biopharmaceuticals. Dr. Hartman’s therapeutic area experience gained at Cardioxyl Pharmaceuticals, Gilead (Myogen), Baxter (Somatogen) and Pharmacia & Upjohn, includes Cardiovascular Diseases, Pulmonary & Respiratory diseases, Gastrointestinal, Endocrinology, Neurology and Ophthalmology, in all phases of development. Dr. Hartman’s successful authorship includes pharmaceutical regulatory submissions of 3 NDAs, and 13 INDs [includes CTA (EU)], Rare Disease Drug Applications, IBs, Special Protocol Assessments, Labels, Combination Products, Biowaivers, Environmental Assessments, funded proposals (including SBIRs), and preclinical reports including TK, and gap analyses.

    Dr. Hartman earned a Doctor of Philosophy, Pharmacology and Toxicology from Medical College of Wisconsin, Milwaukee, WI and a Bachelor of Science, Biology from Purdue University, West Lafayette, IN.

  • Mark Weinberg Profile Picture

    Mark Weinberg, MD

    Chief Medical Officer

    Mark Weinberg, MD

    Chief Medical Officer

    Mark Weinberg is a pharmaceutical and biotech physician/executive with experience ranging from “top 20” pharma companies to micro-cap biotech. Dr. Weinberg has worked throughout the development cycle (pre-clinical through phase III and medical affairs) in multiple therapeutic areas (oncology, immunology, CNS, respiratory, ophthalmology, dermatology, pain, hematology, rheumatology, women’s health including orphan disease development) with significant experience in regulatory interactions with FDA and EMA.

    Previously, Dr. Weinberg served as Senior Vice President of Clinical Development for RestorGenex Pharmaceuticals; Vice President, Global Clinical Science and Global Therapeutic Area Head, CNS and Pain at Astellas; Vice President, Medical Strategy and Medical Affairs at Lundbeck Inc. (formerly Ovation Pharmaceuticals); and held roles of increasing responsibility at Takeda Global Research and Development and Abbott Laboratories. Most recently, he served as Chief Medical Officer at Avillion, and was CMO and Managing Director with the Halloran Consulting Group.

    Dr. Weinberg earned his MD from Duke University and remained there to complete a residency in internal medicine. He also holds an MBA from the Kellogg School of Management at Northwestern University and a BA in economics from Yale University.

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Board of Directors

  • Dr. Grazia Piizzi Profile Picture

    Dr. Grazia Piizzi, PhD

    Dr. Grazia Piizzi, PhD

    Grazia Piizzi, PhD has served as a member of MDI’s board of directors since March 2022. She has more than 18 years of experience in the global pharmaceutical and biotech industry and in her last role she was Executive Vice President, Drug Discovery at Ananke Therapeutics. Prior to joining Ananke, Grazia was Chief Scientific Officer of Juvenescence Limited. She spent 10 years at Novartis Cambridge and Basel leading global teams responsible from target ID to clinical candidate selection across multiple disease areas. Later, Grazia joined Merck Cambridge to build the new Exploratory Science Center (ESC) and worked closely with Merck BD&L and Venture teams. At Merck, she established a multidisciplinary team and platform to identify opportunities in infectious diseases, microbiome, and immune-cancer-microbiome interactions. More recently, Grazia was the SVP of Small Molecules R&D and Head of Inflammation at a Flagship Pioneering startup, Cygnal Therapeutics, decoding the links between peripheral neurons and diseases.

    Grazia received her Ph.D. in Organic Chemistry at UCLA, and subsequently completed her postdoctoral work at MIT on the synthesis and biological properties of natural products. She currently serves on the NIH SBIR committee to review research and commercialization grants for drug discovery and development.

  • Robert L. Zerbe Profile Picture

    Robert L. Zerbe, MD

    Robert L. Zerbe, MD

    Robert Zerbe has served on MDI’s board of directors since April 2022. Dr. Zerbe has served as a member of the board of directors of Cirius Therapeutics, Inc., a developer of therapies for the treatment of liver and metabolic diseases, since May 2016. He also has served as a member of the board of directors of Vericel Corporation, a developer of patient-specific expanded cell therapies for severe diseases and conditions, since January 2006 and as chairman of the board of directors since October 2012. Until July 2016, Dr. Zerbe was the chief executive officer of QUATRx Pharmaceuticals Company, or QUATRx, a drug development company he co-founded in 2000. Prior to his role at QUATRx, Dr. Zerbe held several senior executive management positions with pharmaceutical companies including Eli Lilly and Company, from 1982 to 1993, and Pfizer (formerly Parke-Davis) from 1993 to 2000. During his tenure at Eli Lilly and Company, Dr. Zerbe’s clinical research and development positions included managing director, Lilly Research Center U.K., and vice president of clinical investigation and regulatory affairs. He joined Parke-Davis in 1993, becoming senior vice president of worldwide clinical research and development. Dr. Zerbe has also served on the board of managers of Metabolic Solutions Development Company, LLC since 2015.

    Dr. Zerbe received his M.D. from the Indiana University School of Medicine, and has completed post-doctoral work in internal medicine, endocrinology and neuroendocrinology at Indiana University and the National Institutes of Health.

  • Steve Felstead Profile Picture

    Steve Felstead, MBChB

    Steve Felstead, MBChB

    Steve Felstead has served on MDI’s board of directors since February 2022. Dr. Felstead is currently Chief Medical Officer at Juvenescence Limited. Dr. Felstead was Vice President, Head of Clinical Research in the pharmatherapeutics division at Pfizer Inc., in both the UK and the US. Dr. Felstead was responsible for clinical development and pharmacology, translational and molecular medicine, preclinical and clinical statistics. He led the team that laid the groundwork for the NIH/NCATS program for systematic evaluation of drug repurposing. In addition to his line management and senior leadership roles, Dr. Felstead was involved in multiple projects, as member and team leader, helping to develop Zithromax (azithromycin), Viagra (sildenafil), and Vfend (voriconazole). Dr. Felstead led the Viagra (sildenafil) team when the first pulmonary hypertension study was being designed, which led to the successful Revatio development program. He also led the Celsentri/Selzentry (maraviroc) team through to successful transatlantic registration of this novel anti-retroviral medicine.

    Dr. Felstead is a member of AdALta Limited’s Scientific Advisory Board, a Non-executive director for MGB Biopharma Ltd, CMO for Mironid Limited, and a member of TRICAPITAL Business Angel group, which invests in emerging businesses in the Scottish Borders. Dr. Felstead served as member of Innovate UK’s Biomedical Catalyst Late Stage Award committee from 2014-2019, and served as CMO for Mironid Limited from 2019-2022. Dr. Felstead has a Bachelor of Medicine and Surgery degree from Leeds University in the UK.

  • Stephen Benoit Profile Picture

    Stephen Benoit

  • Gillian Dines Profile Picture

    Gillian Dines

    Gillian Dines

    Gillian Dines has served on MDI’s board of directors since March 2024. Gillian (Gill) Dines is Chief Science Officer of Juvenescence Limited. She is a highly accomplished pharmaceutical executive with more than 30 years of experience in research, development, approval, and commercialization of new medicines in both “Big Pharma” and as an entrepreneur in the Biotech environment. Gill has led the successful development and global approval of more than 10 medicines and devices in a number of therapeutic areas including neuroscience, oncology, immunology, respiratory and rare diseases.

    Before joining Juvenescence, Gill was Senior Vice President and Head of Research and Early Development at Jazz Pharmaceuticals. In this role she led integration and organizational restructuring to build a novel pipeline and capabilities in R&D following the acquisition of GW Pharma where she was Head of R&D Operations. Before her role in GW/Jazz, Gill was VP Head of New Medicines Strategic Planning at UCB and the UK Site Head. In 2008 she was Company Director and Chief Development Officer at RespiVert, a UK based Biotech that delivered clinical phase assets from start-up to acquisition by Centocor Ortho-Biotech (Janssen Pharmaceuticals). Her previous experience covers various leadership roles across all phases of pharmaceutical R&D over a 20-year tenure at GSK. Gill holds a Master of Science in Toxicology from the University of Surrey and a Bachelor of Science from University of Leeds in Biochemistry and Genetics.

Clinical and Scientific Advisory Board

  • Daniel A. Lawrence, PhD Profile Picture

    Daniel A. Lawrence, PhD

  • Dinesh Khanna, MD, MSc Profile Picture

    Dinesh Khanna, MD, MSc

    Dinesh Khanna, MD, MSc

    Dinesh Khanna, MD, MSc is Professor of Medicine and Director of the University of Michigan Scleroderma Program and holds the Frederick G.L. Huetwell Professorship in Rheumatology. He is also President, Friends of World Scleroderma Foundation.

    ​ Dr. Khanna received his medical training at University College of Medical Sciences in 1996 from India and completed his rheumatology fellowship at UCLA. He then completed a Masters in Clinical Research from UCLA. ​

    He is the Principal Investigator on National Institutes of Health and industry-sponsored clinical studies. He has designed and led trials of abatacept, riociguat, pirfenidone and tocilizumab in scleroderma and currently leading multiple trials in scleroderma. He has published over 550 peer reviewed publications and book chapters.

    ​ Dr. Khanna also serves as a reviewer for several professional journals, society committees and training programs, and grant applications and has published in Lancet, JAMA, and NEJM. His current research focus is on developing, validating and refining outcome measures in rheumatic diseases and designing controlled trials.

    ​ He received the 2011 Doctor of the Year award from the National Scleroderma Foundation and the prestigious 2015 Henry Kunkel Young Investigator Award from the American College of Rheumatology. He was recently inducted into the Society of Clinical Investigation.

  • John Varga, MD Profile Picture

    John Varga, MD

    John Varga, MD

    John Varga, MD is Chief, Division of Rheumatology, University of Michigan Medicine. Prior to joining Michigan Medicine in September 2020, Dr. Varga was the John and Nancy Hughes Distinguished Professor of Rheumatology at the Northwestern Feinberg School of Medicine and director of the Scleroderma Program. Dr. Varga earned his BA at Columbia University and his MD from New York University. He completed his internal medicine residency at Brown University and his fellowship in rheumatology at Boston University, followed by a postdoctoral fellowship with Sergio Jiminez at the University of Pennsylvania. Dr. Varga later held faculty positions at the University of Pennsylvania, Jefferson Medical College, and was Chief of the Division of Rheumatology at the University of Illinois Chicago. He later joined Northwestern’s Feinberg School of Medicine as the director of the Scleroderma Program.

    Dr. Varga's research focuses on inflammation, fibrosis, tissue repair, and regeneration. He is well-known internationally for his work on defining TGF-beta-mediated fibrosis. Dr. Varga has published more than 250 peer-reviewed manuscripts in journals such as JAMA, Annals of Internal Medicine, Journal of Biological Chemistry, Journal of Clinical Investigation, Nature Communication, and Science Translational Medicine. His research work is funded by the NIH, and foundation and pharmacological grants.

    Dr. Varga is a nationally recognized academic scholar and has received many accolades for his work on the basic mechanisms of fibrosis and scleroderma. He is an elected member of the Association of American Physicians and a Master of the American College of Rheumatology. Dr. Varga received the Scleroderma Foundation Lifetime Achievement Award and was recognized as Mentor of the Year by the Feinberg School of Medicine. Dr. Varga is the Associate Director of the University of Michigan Scleroderma Program.

    Dr. Varga serves on the Board of Directors for the Global Fibrosis Foundation and the American College of Rheumatology. He has been a member and chair of several NIH study sections, as well as committees from professional organizations. He is currently co-Editor of Arthritis and Rheumatology.

  • David Ginsburg Profile Picture

    David Ginsburg, MD

    David Ginsburg, MD

    David Ginsburg is James V. Neel Distinguished University Professor of Internal Medicine and Human Genetics, Warner-Lambert/Parke-Davis Professor of Medicine, a member of the Life Sciences Institute at the University of Michigan Medical School, and a Howard Hughes Medical Institute Investigator. He received his B.A. degree in molecular biophysics and biochemistry from Yale University in 1974 and his M.D. degree from Duke University School of Medicine in 1978. Dr. Ginsburg is board certified in Internal Medicine, Hematology, Oncology, and Clinical Genetics. His postdoctoral clinical and research training was at the Brigham and Women's Hospital and Children's Hospital, Harvard Medical School. Dr. Ginsburg joined the faculty at the University of Michigan as an Assistant Professor in 1985.

    Dr. Ginsburg’s laboratory studies the components of the blood-clotting system and how disturbances in their function lead to human bleeding and blood-clotting disorders. The lab also studies the plasminogen activation system, the mechanism by which blood clots are broken down, and has explored the role of this system in a variety of disease processes including atherosclerosis and microbial infection.

    Dr. Ginsburg is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, the American Philosophical Society, and recipient of the E. Donnall Thomas Lecture and Prize and Stratton Medal from the American Society of Hematology, the Basic Research Prize and the Distinguished Scientist Award from the American Heart Association, the Stanley J. Korsmeyer Award from the American Society of Clinical Investigation, the AAMC Award for Distinguished Research in the Biomedical Sciences, and the Lucian Award from McGill University. Dr. Ginsburg has served on multiple Editorial Boards and Advisory Councils in both academics and industry including the Board of Directors for Shire plc. He is a past president of the ASCI and has served on the Councils for the AAP, the National Academy of Sciences, and the National Academy of Medicine.

News at MDI

MDI Therapeutics announces closing of Series A investment

Novi, Michigan – March 21, 2022 – MDI Therapeutics, Inc. (“MDI”), a pharmaceutical company developing novel therapies for the treatment of fibrosis and fibroproliferative diseases, is pleased to announce it has closed a Series A financing with Juvenescence Ltd. Juvenescence, a biopharmaceutical company focused on treating aging and age-related disease, will provide MDI with up to $9 million in funding and collaborate with MDI to advance its lead program through Phase 1 clinical trials.

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MDI Therapeutics
46430 Peary Ct.
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