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The Ischemic Leg Muscle is the Target Organ in PAD

Reduced perfusion causes muscle ischemia and leads to a feed-forward pathway of endothelial injury causing an increase in M1-like macrophage polarization and increased reactive oxygen species, each of which worsens muscle microvascular perfusion and ischemia.

Inflammation Driven by # M1

  • Inhibits angiogenesis
  • Increase injurious cytokines that access circulation

Greater Endothelial/Vascular Injury in Muscle

  • loss microvascular density
  • loss of vascular integrity i.e.: greater vascular, permeability

Increased Reactive Oxygen Species (ROS)

A few selected slides will show sites/effects from miR-93 delievry

  • ROS directly injures endothelial cells, makes them leaky, and results in them being less able to deliver oxygen and remove toxins from muscle cells.

Patients with PAD have Increased levels of pro-inflammatory cytokines and lower levels of microRNA-93 in affected muscles

Levels of pro-inflammatory M1-macrophage are increased in ischemic muscle biopsies.

Levels of microRNA-93 are decreased in ischemic muscle biopsies.

microRNA-93 promotes formation of functional, non-leaky blood vessels

microRNA-93 significantly reduces levels of ROS under hypoxia/serum starvation (HSS) conditions

H2DCFD = 2′,7′ -dichlorodihydrofluorescein diacetate is a chemically reduced fluorescein and an indicator for reactive oxygen species (ROS) in cells

* Angiogenic properties of miR-93 in EC under HSS published in Hazarika et al. Circulation 2013;127:1818-28.

Above ROS data is included in recently submitted manuscript.

microRNA-93 treatment reduces levels of pro-inflammatory cytokine and M1-macrophage, while increasing M2-marcorphage levels

Pro-inflammatory cytokine levels are decreased in conditioned media from macrophage treated with microRNA-93 (miR93 Mim) or a scrambled oligonucleotide (Scrbd Mim)

microRNA-93 (miR93 Mim) treatment of human monocytes, increases M2-like macrophage while decreasing M1-like macrophage when compared to a scrambled oligonucleotide (Scrbd Mim)

INTELLECTUAL PROPERTY: Broad Protection for Treating PAD

Compositions and methods for treating peripheral arterial disease

  • Inventors at the University of Virginia: Brian Annex, Charles Farber, Surovi Hazarika
  • US 9,845,465 B2, issued 12/19/17
  • European Patent 2885008B, issued 11/7/2018
  • Covers the use of both miR-93 and pre-miR-93
  • Exclusively licensed from University of Virginia for all fields and all territories.

Methods, Kits, Compositions for Reducing miR106B Activity

  • Inventor: Brian Annex
  • Assignee: Merand Pharmaceuticals, Inc.
  • Provision patent application US 63/148,940 filed on 2/12/2021, with PCT application filed in 2022.

Company ready to initiate First-in-Human, Phase 1, study with lead microRNA product MPMI-93 in patients with Peripheral Arterial Disease (PAD).

2022 All rights reserved

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Doug Losordo, MD

Head, Clinical Advisory Board

Dr. Losordo most recently has held the position of Chief Medical Officer at KBP Bioscienses.  He joined KBP from Caladrius Biosciences, where he served as Executive Vice President, Global Head of Research and Development and Chief Medical Officer since 2013 and was a member of the Company’s Scientific Advisory Board from 2006 to 2013. Prior to Caladrius, he was Vice President, New Therapies Development, Regenerative Medicine, and a member of the Baxter Ventures team at Baxter International. Before beginning his career in the biotech industry in 2011, Dr. Losordo was the director of the Feinberg Cardiovascular Research Institute and the Eileen M. Foell Professor of Heart Research at Northwestern University’s School of Medicine and director of the Program in Cardiovascular Regenerative Medicine at Northwestern Memorial Hospital. Previously he was Professor of Medicine at Tufts University School of Medicine and Chief of Cardiovascular Research at St. Elizabeth’s Medical Center in Boston. He is board-certified in internal medicine, cardiovascular disease, and interventional cardiology. He received his M.D. from the University of Vermont. He has served as an associate editor of Circulation Research, the basic science journal of the American Heart Association, and serves on the editorial boards of a number of scientific journals.

Chuke Nwachuku, DrPH

Chief Development Officer

Dr. Nwachuku is the most recent member of the Merand management team, joining the Company in 2020.  He is an alumnus of the NIH and was the Scientific Project Officer for the ALLHAT trial.  In the biopharmaceutical Industry, Dr. Nwachuku has held leadership and line management roles in Bristol Myers Squibb, Astra Zeneca, and Daiichi Sankyo. He held positions of increasing responsibilities in Clinical Development and Regulatory Affairs. Of note was his leadership in the successful design, regulatory submission, building of the trial infrastructure, trial implementation, conduct, completion, and publication of a global, first-ever, proof of concept trial of a novel oral anticoagulant in PAD/CLI patients undergoing endovascular intervention. He has cultivated relationships with a broad range of thought leaders and academic partners in vascular diseases; and has sponsored two global thought leader workshops on emerging PAD/CLI therapeutics in the United State (NYC) and in Japan (Tokyo). Additionally, Dr. Nwachuku has organized several expert panels (KOL ad boards) globally in cardiovascular, renal, thrombosis and endocrine diseases.

Brian Annex, MD

Chief Medical Officer

Dr. Annex is the scientific founder of Merand and is currently working with the Company as its Chief Medical Officer, providing expertise in non-clinical and clinical development. For approximately two-decades, his research activities as a physician/clinician scientist have largely been focused in the area of PAD focusing on translational vascular biology approaches for the development of novel therapeutic approaches to treat patients with PAD.  Dr. Annex’ laboratories basic science focus is on angiogenesis, the growth and proliferation of existing vascular structures.  His laboratory has more than a decade of continuous multi-R01 NIH funding that has focused on PAD and his interdisciplinary translational research program uses a variable mix of pre-clinical (including in-vivo and in-vitro models) and focused human studies and this was the manner in which his group identified microRNA-93 (miR-93) as a potential human therapeutic.  He currently is Chair and Professor of Medicine and the Medical College of Georgia where he has three RO1 grants as Principle Investigator, 5 in total, which involve studies that focus at the intersection of inflammation, macrophages, and peripheral arterial disease In addition to the above research efforts, Dr. Annex has been involved in more than 10 Phase 1, Phase 2 and Phase 3 studies of PAD and has experience with the FDA and various other regulatory groups.  Dr. Annex has also served as a key opinion leader and consultant/advisor for several multinational pharmaceutical companies and small biotechnology companies.

Tony Giordano, Ph.D.

President and CEO

Dr. Giordano is a co-founder of Merand. He has held senior management positions at eight separate biotechnology companies, including Message and Nucleonics, two companies focused on RNA platforms; Alteris, a cancer vaccine compound acquired by Celldex; TheraVasc, a PAD company which licensed its intellectual property to JanOne that is entering Phase 2 development with the lead product; and Sulfagenix, that developed a medical food that was marketed by a company with a medical food sales force.  At these and the other companies he led, he has been responsible for business planning, licensing, directing research and development efforts, fundraising and financial management. He was a consultant/advisor to three venture funds, a consultant to the Biomedical Research Foundation, and was appointed by the Governor of Louisiana to the Innovation Council. Dr. Giordano has secured over $7M in federal funding for the Companies he has managed and has 20 issued and several pending patent applications. Before beginning his career in biotech, Dr. Giordano was a senior scientist at Abbott Laboratories.  He has also served as Assistant Dean of Research and Business Development at LSU Health in Shreveport and as Senior Director of Special Projects in Innovations at the Cleveland Clinic.

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