BioMarin Pharmaceutical Inc. announced that it has acquired ZyStor Therapeutics, Inc. (ZyStor), a privately-held biotechnology company developing enzyme replacement therapies (ERT) for the treatment of lysosomal storage disorders. ZyStor's lead product candidate is ZC-701, a novel fusion of insulin-like growth factor 2 and alpha glucosidase (IGF2-GAA) in development for Pompe disease.

Under the terms of the agreement, BioMarin acquired ZyStor for $22 million upfront and up to an additional $93 million if certain development, regulatory and commercial milestones are achieved. There are no royalties owed. The FDA has accepted an investigational new drug (IND) application for ZC-701, investigational product has been manufactured and a clinical study is expected to start in Q1 2011.

In vitro studies demonstrate that ZC-701 has more than ten times higher affinity for the mannose-6-phosphate receptor compared to Myozyme, which enables delivery of higher levels of enzyme to the lysosomes of muscle cells of Pompe patients. Studies in the Pompe mouse model indicate that ZC-701 clears glycogen to lower levels in skeletal, heart and diaphragm muscle compared to Myozyme and at similar levels compared to second generation compounds that have been tested. Many experts believe that an enzyme with more efficient uptake into muscle cells would lead to more effective treatment of the disease. Over the next several months BioMarin plans to recruit clinical research hospitals that can conduct clinical studies and finalize the clinical protocol and expects the first patient dosed in the first quarter of 2011.

"The acquisition of ZyStor gives us the opportunity to introduce a superior product to fulfil an unmet medical need and is a perfect fit in our core business. It not only provides us with a promising product candidate for Pompe disease but also an exciting new platform technology," said Jean-Jacques Bienaime, chief executive officer of BioMarin. "ZC-701 has been shown to be more effective in the Pompe mouse model than commercially available replacement enzymes for Pompe disease. In addition, ZyStor's proprietary Glycosylation Independent Lysosomal Targeting (GILT) technology is applicable to other ERTs and has the potential to deliver more enzyme to lysosomes compared to traditional mannose-6-phosphate targeted approaches. Also, relative to our internal candidate for Pompe, BMN-103, ZC-701 has a faster clinical development timeline, lower development costs, significantly lower cost of goods and lower capital investment."

Bienaime continued, "As for the potential market opportunity, the incidence of Pompe is 1 in 40,000 births. The total market for Pompe is estimated at more than $1.0 billion, assuming 3,000 to 6,000 patients have access to high value therapeutics and an average cost of therapy that is comparable to other enzyme replacement therapies. We look forward to keeping you updated on this and other programs in our pipeline."

Loren Peterson, president and chief executive officer of ZyStor said, "We are very pleased to conclude this transaction with BioMarin for the development of ZC-701. BioMarin has a proven track record of successfully and expeditiously developing value-added therapies for orphan diseases, with particular strength in the field of enzyme replacement therapies for lysosomal storage disorders. Using our proprietary GILT technology, we believe that ZC-701 has the potential to be a more potent therapy for the treatment of Pompe disease."

Pompe disease, a lysosomal storage disorder, is a progressive degenerative disease of the heart muscle, diaphragm and skeletal muscle. It is caused by a deficiency in the lysosomal enzyme acid alpha glucosidase which leads to the accumulation of glycogen in myocyte lysosomes and results in cell death. The incidence is one in 40,000 births. There are two main forms of Pompe disease: adult onset with an incidence of one in 57,000 births and infantile onset with an incidence of one in 138,000 births. The current standard of care is Genzyme's Myozyme and Lumizyme. Prognosis with standard of care is stabilization of the disease or minor improvements for the majority of adult onset patients.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio comprises four approved products and multiple clinical and pre-clinical product candidates.

ZyStor Therapeutics, Inc. is a privately held biotechnology company based in Milwaukee, Wisconsin developing a novel class of targeted protein therapeutics incorporating the company's proprietary Glycosylation Independent Lysosomal Targeting (GILT) technology.