Developing novel serpin-based therapies for the treatment of fibrosis and fibroproliferative disorders

About MDI

MDI Therapeutics is a pharmaceutical company developing novel serpin-based therapies for the treatment of fibrosis and fibroproliferative disorders. 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 is Essential in 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

    Interim Chief Medical Officer

    Mark Weinberg, MD

    Interim 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

    Dr. Grazia Piizzi, PhD has served as a member of MDI’s board of directors since March 2022. Dr. Piizzi has more than 15 years of experience in the global pharmaceutical and biotech industry and is currently Executive Vice President, Drug Discovery at Ananke Therapeutics. Prior to joining Ananke, Dr. Piiizi was Chief Scientific Officer of Juvenescence Ltd. Dr. Piizzi spent 10 years at Novartis Cambridge and Basel leading global teams responsible from target ID to clinical candidate selection across multiple disease areas. Later, she joined Merck Cambridge to build the new Exploratory Science Center (ESC) and worked closely with Merck BD&L and Venture teams. At Merck, Dr. Piizzi established a multidisciplinary team and platform to identify opportunities in infectious diseases, microbiome, and immune-cancer-microbiome interactions. More recently, Dr. Piizzi 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.

    Dr. Piizzi 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 in 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 Head of Development Projects at Juvenescence, Ltd. Dr. Felstead retired as Vice President, Head of Clinical Research, Pharmatherapeutics Division, Pfizer Inc. after a 25-year career with the company. Dr Felstead was appointed Head of Clinical Research in January 2009 responsible for the disciplines of Clinical Development and Pharmacology, Translational and Molecular Medicine, Preclinical and Clinical Statistics. Clinical Research was responsible for research projects up to Proof of Concept (Phase 2a) in the following Therapeutic Areas: Neuroscience, Cardiovascular and Metabolic Disease, Anti-Infectives, Pain and Regenerative Medicine.

    During his time with Pfizer, Dr. Felstead led the team that laid the groundwork for the NIH/NCATS program for systematic evaluation of drug repurposing. From 2007 – 2008 Dr. Felstead served as Development Therapeutic Area Head for Allergy and Respiratory medicines through to Phase 3b. Previously he held a number of project, line and administrative roles within drug development in the Sandwich, UK office over 15 years, and in Groton/New London, CT office for 3 years. These roles included Zithromax (azithromycin) clinical project manager in Europe, head of clinical development in Sandwich, Viagra (sildenafil) development team leader, Vfend (voriconazole) development team leader and Groton/New London development site head. Dr. Felstead led the Viagra (sildenafil) team when the first pulmonary hypertension study was being designed, which led to the successful Revatio development program. From 2003-2007 he led the Celsentri/Selzentry (maraviroc) team through to successful transatlantic registration of this novel anti-retroviral medicine.

  • Stephen Benoit Profile Picture

    Stephen Benoit

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 serpin-based therapies for the treatment of fibrosis and fibroproliferative disorders, 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.
Novi, MI 48377