Corporate Overview

Mirus Bio Corporation is a biopharmaceutical company focused on discovering, developing and commercializing innovative nucleic acid based technologies and products. Under development are RNAi gene silencing therapies based on Mirus’ proprietary Dynamic PolyConjugates™ delivery platform and gene therapies utilizing its Pathway IV™ delivery protocol. Commercially, Mirus markets a range of innovative transfection and labeling research reagents worldwide.

Dynamic PolyConjugates (“DPC”) is a targeted systemic siRNA delivery platform. Our proprietary polymer based formulation chemistry efficiently targets gene silencing complexes to specific cells. As the DPCs attach to and enter the target cells, they respond to the environmental cues provided by the cell to disassemble and release the active siRNA molecule. This unique chemistry mimics the natural viral targeting and disassembly process. This technology is currently being optimized for liver and cancer tissues, and is actively being evaluated by select partners for research and clinical indications.

Pathway IV is a clinically practical procedure based upon intravenous (“IV”) delivery of plasmid DNA (“pDNA”) to targeted limb muscle. With blood flow temporarily occluded by a tourniquet, a DNA solution is rapidly injected into a suitable vein. This elevates the pressure within the occlusion zone, making the blood vessel wall more permeable and allowing the pDNA to migrate into the adjoining muscle cells. Blood flow is then restored to normal within a few minutes, with only mild transient affects to the vasculature.

This quick, robust procedure is being used as an enabling platform that will provide first-in-class therapeutic treatments for muscular dystrophy, peripheral ischemia and other diseases.

Patients with the most common muscular dystrophies, Duchenne and Becker, suffer from a genetic defect in which dystrophin protein is either poor or inadequate in their muscle cells. It affects roughly 1 of every 3500 male births. MyoDys® will treat this disease by inserting a gene encoding active dystrophin into affected muscles to delay or prevent loss of muscle function.

Peripheral ischemia is a condition in which reduced blood supply to limbs causes claudication (cramping), chronic pain, and potentially loss of the limb. It is common in diabetics and the elderly, where up to 20% of those over age 70 experience intermittent claudication. Mirus’ treatment is based upon delivery of a gene encoding an angiogenic factor to the affected limb, which induces revascularization of the limb. In the future, the company envisions using muscle as the host site for gene therapies that induce secretion of therapeutic proteins to treat a range of diseases, including anemia, arthritis, ALS, and cancer immunotherapeutics.

Mirus R&D uniquely integrates nucleic acid delivery and chemistry, a core competency which is unmatched in the industry. This serves as the foundation for both its novel research reagents and emerging therapeutics. The company maintains advanced research programs focused on synthetic siRNA delivery, and on gene delivery to liver and other target tissues.
Access to Mirus’ technologies is available through strategic alliances as well as licensing in nonstrategic fields. Mirus is well positioned to be a partner of choice due to its consistent record of profitability; driven by the sales growth of its research reagents.

RESEARCH REAGENTS & SERVICES

Mirus is a recognized leader in developing innovative nucleic acid research reagents, distinguished by its many accomplishments:

• First to develop an siRNA transfection reagent (2001)
• Pioneered development of high efficiency/low toxicity transfection formulations
• First to market a single step nucleic acid labeling technology
• Unique technology to label native, biologically relevant short RNA species such as micro RNA

Mirus’ TransIT® reagents are unique lipid and polymer formulations that achieve superior delivery efficiency of pDNA and siRNA with minimal cytotoxic effects. They have been optimized for in vitro delivery in a variety of mammalian cells as well as for in vivo delivery in small animals.

The company’s Label IT® kits employ proprietary chemistry to covalently attach labeling molecules to DNA and RNA. This simple one-step process is faster and more robust than traditional multi-step enzymatic labeling, and can be used for intracellular tracking, chromosome analysis, and microarray labeling.

Achieving RNA interference in vivo is a major industry challenge. In this regard, Mirus has developed a breakthrough technology that uses the bloodstream to efficiently deliver siRNAs into specific tissues in adult animals. Using its patented hydrodynamic injection technology, the Company can routinely achieve 60-80% gene knockdown in the liver cells of research animals. This level of knockdown is unprecedented using a non-viral delivery technology and is faster, cheaper and more versatile than the previous industry standard, knockout mice. Thus, it represents an exciting new tool for metabolic pathway analysis and target identification and validation. This capability is offered both as a service and for license. The proprietary Label IT technology enables a unique capability to track the delivery and intracellular update of these constructs.

CORPORATE HISTORY

Internationally recognized gene therapy specialist, Jon Wolff, along with his colleagues James Hagstrom and Vladimir Budker founded the company in 1995, based on research they performed at the University of Wisconsin-Madison. Mirus’ scientific leadership has been at the forefront of the gene therapy field since its inception. In 1990, Dr. Wolff and colleagues were the first to discover that muscle cells in the body could take up genes efficiently, an invention which helped launch direct injection approaches for gene therapy.

Mirus was founded on the principle that non-viral (i.e. plasmid DNA based) methods offer distinct advantages over viral methods of gene transfer. Following this path, Mirus has pioneered the development of a wide range of non-viral delivery technologies using proteins, polymers, and lipids in conjunction with novel chemistries that provide unique nucleic acid delivery capabilities in vitro and in vivo.

THERAPEUTIC PRODUCTS IN DEVELOPMENT

• MyoDys® Muscular Dystrophy Therapy
  • Market: $250-$500M
  • Stage: Phase I/II in preparation
  • Partner: Transgene
• Peripheral Ischemia Therapy
  • Market: >$1B
  • Stage: Research
  • Partner: Independent

TECHNOLOGY PORTFOLIO

• Dynamic PolyConjugates™ targeted systemic siRNA delivery platform
• Pathway IV™ intravenous regional delivery method for pDNA or viral vectors
• Hydrodynamic tail vein injection of synthetic siRNA or siRNA expression vectors for target ID & validation; also pDNA for gene expression, construct evaluation, or antibody production
• Nucleic acid delivery and labeling chemistries

MARKETED RESEARCH PRODUCTS

• TransIT® Transfection Reagents
  • pDNA and DNA vectors
  • siRNA, mRNA and viral RNA
• Label IT® Labeling Reagents
  • DNA & RNA, including miRNA

CORPORATE INFORMATION

FOCUS

Specialists in nucleic acid chemistry and delivery

TECHNOLOGY PORTFOLIO

RNAi Therapeutics
Synthetic siRNA Delivery
shRNA Expression Vector Delivery
Gene Therapy
Genetic Vaccines
Gene Delivery
Transfection Reagents
Labeling Reagents

MANAGEMENT

Russell R. Smestad
President

Jon A. Wolff, MD
Chief Scientific Officer

James E. Hagstrom, PhD
VP Scientific Operations

Richard S. Schifreen, PhD
VP Research Products

Scott A. Rose
VP Finance & Administration

No. Employees: ~50

OWNERSHIP

Privately held