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GEN News Highlights : Apr 7, 2011

Pfizer to Attack Lysosomal Storage Diseases with Zacharon’s Small Molecule Approach

Firm’s previous two investments in orphan drug development have not yet succeeded.

Zacharon Pharmaceuticals entered into a collaboration with Pfizer to develop drugs for orphan diseases including lysosomal storage disorders. The potential value of the collaboration to Zacharon is approximately $210 million. The firms did not divulge how much will be given up front and how much is attributed to funding and milestones.

While Pfizer has invested upward of $60 million since December 2009 to boost its position in the orphan disease market, it has not yet seen the success it had hoped for. It bought two companies that had products already under FDA review, one for a lysosomal storage disorder and another for a protein misfolding disease. Both drug candidates have had setbacks in approval, however.

Pfizer is now banking on Zacharon’s approach to treating orphan diseases. Rather than the historical approach of correcting the enzyme deficiency, which was the case with the previous drug acquired by Pfizer, Zacharon is developing small molecules that selectively modify the structure of the glycan so that the deficient enzyme is not required for degradation.

This strategy, termed substrate optimization therapy, reportedly represents the first small molecule approach to treating lysosomal storage diseases. This fundamental difference of using a small molecule creates the potential to penetrate the central nervous system and other critical tissues largely unaddressed by existing therapies, according to Zacharon. In addition to funding and success-based fees, the firm will receive royalties if any of the products that result from its partnership with Pfizer get commercialized.

Established in 2004, Zacharon’s other funding sources include SBIR grants and venture financing from Avalon Ventures. Zacharon reports that its assay technologies integrate cell-based screening with highly sensitive glycan structural analysis tools. Its most advanced drug development programs target several forms of lysosomal storage disease and several rare forms of cancer.

The glycan-targeted assay technologies are also being applied to develop clinical biomarkers and diagnostics for glycan-related diseases. One such diagnostic with applications in newborn screening is being developed in collaboration with Mayo Clinic’s Department of Laboratory Medicine.

Pfizer entered drug development for orphan diseases in December 2009 through the $60 million acquisition of Protalix. The main candidate of interest in Protalix’ pipeline was taliglucerase alfa for the treatment of Gaucher disease, a lysosomal storage disorder. The compound was touted as being able to fill the treatment gap created by the shortfall of the marketed drug, Cerezyme, due to drugmaker Genzyme’s plant closure.

In March 2010, about three months after Pfizer's purchase of Protalix, the agency approved the one other candidate it was reviewing for Gaucher disease: Shire’s enzyme replacement therapy, VPRIV. While Pfizer agreed to pay another $55 million in milestones related to regulatory success of taliglucerase alfa, in February of this year FDA sent a complete response letter detailing clinical queries and issues associated with chemistry, manufacturing, and control.

Pfizer made another bet in the orphan disease space in September 2010, picking up FoldRx Pharmaceuticals. The company is developing drugs to treat diseases caused by protein misfolding. On April 4, however, Pfizer received a refusal to file letter for lead candidate tafamidis, a treatment for transthyretin familial amyloid polyneuropathy.