Urokinase

Opportunity Overview

Microbix Biosystems Inc. (TSX: MBX) seeks a partner for its Urokinase assets, previously owned by Abbott Laboratories under the name of Abbokinase®. The Company has assembled a complete solution to serve the Urokinase market through a cell line based approach: existing FDA and Health Canada approvals; preparation for filing outside the U.S.; opinion leader relationships; formulary listings in US hospitals; remaining Abbott product inventory; optimization, calibration and validation of Microbix’s Urokinase production facility for existing market supply and capacity for further markets; intellectual property for new indications, particularly in ophthalmology and oncology; raw materials and intellectual property for production; and, the most expert group in the world on Urokinase

Microbix’s Urokinase program was considerably accelerated with the acquisition of ImaRx Therapeutics Inc. (Tucson, AZ) Urokinase assets in September of 2008.  The acquisition included the inventory of Kinlytic™ (Urokinase for Injection), formerly known as Abbokinase®, the regulatory approval (NDA) in the United States and key raw materials to support manufacturing. Microbix acquired Urokinase assets from ImaRx with a goal to manufacture and further develop FDA-approved Urokinase for multiple new and previously approved clinical indications for the North American market. The drug is currently approved and registered in the United States for treatment of pulmonary embolism (PE) and in Canada, where the file is now active for clot lysis and catheter clearance.

Microbix is actively seeking a pharmaceutical company with a presence in the critical care market to acquire the entire portfolio of assets for the purposes of reintroducing Urokinase to the North American market through site transfer of the existing NDA file.

Urokinase Background

Urokinase, a successful thrombolytic drug, was first approved in the U.S. in 1978 for PE and coronary occlusion. It was, used substantially off label for dissolving large peripheral thrombi in arms and legs, and until 1998 it was the standard of care for catheter clearance where it is used to re-establish flow in occluded biomedical catheters. Over 4 million patients have been treated successfully with Urokinase. Many physicians remain loyal to Urokinase due to the drug’s superior and well-documented safety profile as well as cost and efficacy.

Urokinase was withdrawn from the market in 1999 due to GMP violations at Abbott Laboratories in Chicago that were unrelated to product performance. Annualized sales of the drug dropped from a robust and growing $300 million to zero in a matter of weeks.  In 2002, after resolving its quality system issues and clearing with the FDA, Abbott resumed the sale of Urokinase.

Between 1999 and 2002, the Abbott issue opened the door to new drugs to enter the market.  Physicians started using another drug produced by Genentech, called CathFlo Activase, as a thrombolytic drug used in catheter clearance. Since 2001, the market is comprised mainly of Genentech’s CathFlo product and continues to grow rapidly (as it did in the late 1990’s) to US$115 million in 2006. Tissue Plasminogen Activator (rTPA) drugs marketed by Genentech have shown their limit and are seen by physicians as riskier than Urokinase due to the potential to cause heavy bleeding at high dosage.  Surveys have shown that physicians would be willing to return to the use of Urokinase if the product were more widely available.

In 2006, ImaRx acquired the finished goods inventory from Abbott, renamed the product Kinlytic™ and started marketing it.  What ImaRx did not possess was the manufacturing expertise and facility to manufacture new inventory and drive the success of the product.  As a result, they decided to sell the remaining inventory and all associated assets to Microbix in 2008.

Microbix is now the only group capable of marketing and manufacturing Urokinase.  Furthermore, by utilizing the sNDA process on an already FDA-approved file, new target indications in thrombolysis (i.e. catheter patency prophylaxis) will only require the replication of straightforward phase III clinical trials that have been executed successfully before.  More complex indications in oncology will require phase I/II studies.  Evidence of efficacy in trials will strongly drive value and will open the opportunity for competition with the multi-billion dollar oncology drug, Avastin®.

From the transaction with ImaRx, Microbix has now inherited and currently holds a 7-year old inventory of Urokinase.  The U.S. FDA is ruling that inventory above 4 years could not be sold in the U.S. Microbix has challenged this position numerous times by proving through stability dating enhancement protocols that the inventory of Urokinase is still safe and potent at 7 years.  These studies are ongoing, with 8 year data about to be released. Statistical trend analysis predicts complete stability well beyond 10 years, with expectations up to 20 years, when stored appropriately. Microbix’s inability to sell in the U.S. the inventory purchased from ImaRx, has challenged Microbix Urokinase manufacturing and sales ambitions.

Microbix is now looking for a Partner who could help take this project to the next level and make Urokinase succeed.

Microbix Partner Opportunity

The estimated market size for Urokinase use in the U.S. alone is about $400 million between three indications:  PE, catheter clearance and catheter prophylaxis.  A sales forecast to achieve this is presented below. The same active pharmaceutical ingredient can be used in new, and even larger, indications in oncology, ophthalmology and acute ischemic stroke – a very large, under served market with few treatment options. There are positive clinical outcome data and an approved file on record for Urokinase use in acute ischemic stroke, with several physicians currently using the drug off-label for this disease.  As far as ophthalmology and oncology (solid tumor) indications are concerned, the data available is on a preclinical level.

Sales Forecast (program starting today, $M US)

The opportunity for a partner, in the simplest case, would be to acquire global or regionally exclusive arrangements to manufacture product and develop further indications.  Alternatively a partner could work directly with Microbix to manufacture the product. With this arrangement, in either case, Microbix would supply all necessary documentation to support production, quality and regulatory purposes. Microbix would also supply enough raw materials from inventory worth several years of manufacturing including the tissue banks of human kidney cells, and key reagents to establish initial manufacturing campaigns. Finally, Partners would be trained in the process at Microbix’ facilities in Toronto. Under the acquisition scenario, the Partner would acquire all the Urokinase assets, which may or may not include the state-of-the-art facility, specifically designed by Microbix to manufacture Urokinase.

Microbix’ Assets

Since the mid 90’s, Microbix has developed its own process to produce a generic version of Abbott Urokinase.  In 2002 through this unique expertise, Microbix designed a state-of-the-art, $12.5M Urokinase facility.  Microbix’ Urokinase manufacturing facilities, and all equipment, at 115 Skyway (shown here) were designed for the Urokinase product manufacture and for the purpose of commercializing Urokinase products.

The facility is a 17,000 sqft cGMP manufacturing plant, with ¾ of the space dedicated to production and QA/QC.  The manufacturing output could be up to $80M worth of Urokinase a year.  At full capacity the facility would use 27 employees, with 5 to 10 being dedicated to QA/QC.  This facility has been audited numerous times by clients.  To date the facility is maintained by 5-10 fully trained employees.  In a situation of a plant acquisition, most of these employees would be transferred to the new owner.

Microbix now owns all inventory of Abbokinase®/Kinlytic™ labeled product, testing equipment, Abbokinase® labeled product and unlabeled Urokinase drug product inventory, cell banks, testing references and standards, work-in-process, samples, retained samples of previously released drug substance and drug product batches   In addition, Microbix also now owns all intellectual property rights, including methodologies, processes, protocols, specifications, techniques, patents, trademarks, service marks, trade secrets and know how; all regulatory filings, including IND and NDA filings; records, reports, data bases, clinical data, history, protocols and reports, adverse event reports history, formulae and product development history; all marketing and sales materials, and all contracts with third parties. Microbix owns all global rights to Abbokinase®/Kinlytic™.

Following signature of a Confidential Disclosure Agreement with any interested parties and receiving a stated interest in respect to the potential relationship between the Partner and Microbix, Microbix would be pleased to provide Partner(s) access to a Due Diligence Package, relevant to the relationship contemplated by the Partner. This Package which could be provided by email, though certain information must be reviewed on site at Microbix’ office, and would include:

• General Overview of Microbix and Urokinase
• Financial information on manufacturing and marketing of  Urokinase
• Market Overview
• Intellectual Property Information
• Technical Data on Urokinase
• Facilities and Standard Operating Procedures (SOPs)
• Regulatory History
• Clinical & Regulatory Strategy
• Key Publications

Intellectual Property

Microbix initiated a generic strategy to develop Urokinase shortly after Abbott’s Urokinase patents expired in 1993.  No company other than Microbix has worked to develop the product.  There are closely held trade secrets, proprietary raw materials and atypical facility requirements that are essential to the successful production of commercial Urokinase presenting significant barriers to entry for any would-be competitor.  The intellectual capital in Microbix is substantial; all of the senior scientific and technical people retained by Microbix will continue to be dedicated to the Urokinase program.

Other large indications in oncology and ophthalmology are protected until at least 2020.

Microbix Urokinase Management

Microbix has a uniquely experienced senior management group in Urokinase. They combine the knowledge of how to produce the drug – the only group other than Abbott Laboratories to successfully do so – with extensive experience in product development and GMP manufacturing and thrombolytic sales and marketing.

Mark A. Cochran, PhD Chief Business Officer

Previous positions include CEO of the Blanchette Rockefeller Neurosciences Institute, Managing Director of NeuroVentures Fund, Vice President at MDS Capital Corp, VP, Business Development at Bayer Corp., Director – rFactor VIII at Miles Inc., Head of Department – Molecular Biology and Biochemistry for Bayer (Germany) and Director, Molecular Biologicals at Molecular Therapeutics, Inc (New Haven, US).

Kevin J Cassidy Vice President, Biopharmaceuticals

Mr. Cassidy has been with the company for 25 years and has overall responsibility for all facets of the Urokinase timeline to market. He has held various positions with the Company involving responsibility for Operations, Business Development, Sales, R&D and Quality.

Strategic Advisory Board

Andrew Sternfield – ImaRx and Genentech, thrombolytics sales and marketing
Patrick Kung, PhD – Johnson & Johnson Pharmaceutical Research, Vice President of Research at Centocor, T-Cell Sciences
Martin Marino – Merck KgAa, Apotex
Joseph Renner – Zydus US, Geneva Novartis
Jon Ryan, PhD – Abbott Laboratories
Sam Teichman, MD, PhD – Genentech
William R. (Rick) Srigley, Bayer Corporation.