Synageva BioPharma™ Highlights SBC-103 Data at the Lysosomal Disease Network (LDN) WORLD Symposium™

LEXINGTON, Mass.--(BUSINESS WIRE)--

Synageva BioPharma Corp. (Synageva) GEVA, a biopharmaceutical company developing therapeutic products for rare diseases, today announced SBC-103 data from an oral and poster presentation at the LDN WORLD Symposium being held February 11-13 in San Diego, California. Synageva is investigating SBC-103 as an enzyme replacement for the alpha-N-acetyl-glucosaminidase (NAGLU) enzyme for mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome). MPS IIIB is caused by a decrease in NAGLU enzyme activity which leads to the buildup of abnormal amounts of heparan sulfate in the brain and other organs. The SBC-103 preclinical data presented at the meeting confirms results from previous studies, describes a potential mechanism for central nervous system uptake, and supports further clinical investigation of SBC-103 with intravenous administration.

As part of an oral presentation, Sandra Rojas-Caro, MD, Head of Clinical Research and Development at Synageva presented data from a preclinical study with SBC-103 in a mouse model of MPS IIIB. Data from this study confirmed that SBC-103 delivered by intravenous and intrathecal administration reduced abnormal heparan sulfate levels in the brain of NAGLU-deficient mice. In addition, intravenously administered SBC-103 increased NAGLU enzyme activity levels in the brain of a MPS IIIB mouse model and increased cerebral spinal fluid NAGLU enzyme activity in non-human primates in preclinical studies. These findings suggest that SBC-103 may have properties that allow it to cross the normal blood-brain barrier.

Additional data supporting this observation was provided as a poster from a study that investigated SBC-103 in an in vitro model of the blood-brain barrier. In this study, SBC-103 was effectively transported from the apical side (representing the blood) to the opposite basolateral side (representing the brain tissue). The addition of mannose-6-phospate inhibited directional transport by more than 90%, suggesting that the observed transport of SBC-103 was mediated by the mannose-6-phosphate receptor. These data suggest that the previously reported effects of intravenous SBC-103 on central nervous system substrate accumulation in an MPS IIIB disease model may be mediated by specific cellular transport across the blood-brain barrier.

SBC-103 for MPS IIIB

The mucopolysaccharidoses (MPS) consist of a group of rare LSDs caused by a deficiency of enzymes needed to break down complex sugars called glycosaminoglycans. The MPS III syndromes (also known as Sanfilippo syndromes) share complications with other MPS diseases but represent a clinically distinct subset with marked central nervous system degeneration. Mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome) is caused by a decrease in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity which leads to the buildup of abnormal amounts of heparan sulfates (HS) in the brain and other organs. The accumulation of abnormal HS, particularly in the central nervous system, leads to severe cognitive decline, behavioral problems, speech loss, increasing loss of mobility, and premature death.

SBC-103 is a recombinant form of the human NAGLU enzyme being developed by Synageva as an enzyme replacement therapy for MPS IIIB. Using various dosing approaches, SBC-103 reduced HS substrate storage in the brain, liver and kidney in an MPS IIIB animal model. SBC-103 has been granted orphan designation by the FDA and the EMA.

Sebelipase alfa for LAL Deficiency

LAL Deficiency is a rare autosomal recessive lysosomal storage disease (LSD) caused by a marked decrease in LAL enzyme activity. LAL Deficiency presenting in children and adults, historically called Cholesteryl Ester Storage Disease (CESD), is an underappreciated cause of cirrhosis and accelerated atherosclerosis. These complications are due to the buildup of fatty material in the liver, blood vessel walls and other tissues as a result of the decreased LAL enzyme activity. Infants presenting with LAL Deficiency, historically called Wolman disease, show very rapid progression with death, usually in the first six months of life. Affected infants develop severe malabsorption, growth failure and liver complications.

Sebelipase alfa (SBC-102) is a recombinant form of the human LAL enzyme being developed by Synageva as an enzyme replacement therapy for LAL Deficiency. Synageva is evaluating sebelipase alfa in global Phase 3 clinical trials in infants, children and adults with LAL Deficiency. Sebelipase alfa has been granted orphan designation by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour and Welfare. Additionally, sebelipase alfa received fast track designation by the FDA, and Breakthrough Therapy designation by the FDA for LAL Deficiency presenting in infants.

Synageva's additional pipeline programs and manufacturing platform

Synageva's additional pipeline programs include other proteins targeting rare diseases at various stages of preclinical development. These diseases are characterized by significant morbidity and mortality and these programs are selected based on scientific rationale, high unmet medical need, potential to impact disease course and strategic alignment with the company's corporate focus. In addition to these novel pipeline programs, Synageva is leveraging its manufacturing platform to develop improved biologic therapies for diseases with high unmet medical need.

Synageva's proprietary manufacturing platform utilizes technology to produce drug product with consistent characteristics that enable robustness and flexibility during scale-up. In addition, the platform can provide favorable structural properties for bio-distribution and cell targeting in comparison to glycoproteins produced from other sources.

Synageva routinely posts information that may be important to investors in the “Investor Relations” section of the company's web site at www.synageva.com. Synageva encourages investors and potential investors to consult this web site regularly for important information about the company.

Further information regarding Synageva BioPharma Corp. is available at www.synageva.com.

Forward-Looking Statements

This news release contains “forward-looking statements”. Such statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “intend,” “believe,” “may,” “will,” “estimate,” “forecast,” “project,” “suggest,” or words of similar meaning. These forward-looking statements address, among other matters, the potential mechanism for central nervous system uptake, the potential properties for SBC-103 to allow it to cross the blood-brain barrier, the potential for further clinical investigation of SBC-103 with intravenous administration, our plans for leveraging our manufacturing platform to advance our pipeline programs and develop improved biologic therapies, and our belief that our platform can provide favorable structural properties for bio-distribution and cell targeting in comparison to glycoproteins produced from other sources. Many factors may cause actual results to differ materially from those expressed or implied by forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, including, risk of failure of later preclinical or clinical studies to confirm positive results from earlier preclinical studies or clinical trials, delays in completing preclinical studies, risk that the outcomes of our preclinical studies may not support further development of our product candidates due to safety, efficacy or other reasons, the content and timing of decisions by the U.S. Food and Drug Administration and other regulatory authorities, the ability to maintain the current favorable protein structural properties for bio-distribution and cell targeting as compared to glycoproteins produced from other sources, and the risks identified under the heading “Risk Factors” in Synageva's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 4, 2013 and other filings Synageva periodically makes with the SEC, and others of which are not known. Further analyses of the data described in this press release may lead to different (including less favorable) interpretations of the data. Preclinical and clinical trial data are subject to differing interpretations, and regulatory agencies, as well as medical and scientific experts, may not share the Synageva's views regarding this data or its implications. Synageva may encounter problems or delays in preclinical and clinical development and the regulatory process. No forward-looking statement is a guarantee of future results or events, and investors should avoid placing undue reliance on such statements. Synageva undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Our business is subject to substantial risks and uncertainties, including those referenced above.

“Dedicated to Rare Diseases®” is a registered trademark of Synageva BioPharma Corp. “Synageva BioPharma™” is a trademark of Synageva BioPharma Corp.