Synageva BioPharma™ Announces Six-Month Data from Extension Study of SBC-102 (sebelipase alfa) in Late Onset LAL Deficiency at

  Synageva BioPharma™ Announces Six-Month Data from Extension Study of SBC-102
  (sebelipase alfa) in Late Onset LAL Deficiency at the AASLD Annual Meeting

     -Sebelipase alfa continues to correct a broad range of abnormalities
                      associated with late onset LAL D-

  -Sebelipase alfa well-tolerated at six months and every other week dosing-

Business Wire

LEXINGTON, Mass. -- November 10, 2012

Synageva BioPharma Corp. (“Synageva”) (NASDAQ:GEVA), a clinical stage
biopharmaceutical company developing therapeutic products for rare diseases,
today announced six month results from an ongoing extension study of
sebelipase alfa in adults with late onset Lysosomal Acid Lipase (LAL)
Deficiency at the American Association for the Study of Liver Diseases (AASLD)
annual meeting being held in Boston, MA, November 9-13, 2012.

“We are encouraged by the safety and efficacy profile of sebelipase alfa with
longer term dosing in this trial of adults with late onset LAL Deficiency,”
said Anthony Quinn, MBChB, PhD, FRCP, Senior Vice President and Chief Medical
Officer of Synageva BioPharma. “Sebelipase alfa replaces the deficient enzyme
in these patients, and as anticipated, we observe normalization of serum
transaminases, which are markers of liver damage, along with decreases in
LDL-C and improvements in other lipid abnormalities associated with LAL
Deficiency. We are also pleased to see that with sebelipase alfa treatment the
improvements in blood disease activity markers are accompanied by decreases in
liver fat content and liver volume as assessed by imaging studies. We look
forward to providing additional updates from this ongoing trial as
appropriate.”

Details from the extension study of sebelipase alfa in adults with late onset
LAL Deficiency

Nine adults with LAL Deficiency were enrolled in the Phase I/II trial. After
completing four weeks of treatment in the initial portion of the trial and at
least four weeks of a post-treatment observation period, patients were allowed
to continue treatment with sebelipase alfa as part of a long-term open-label
extension study.

In the extension study, patients received four once-weekly infusions of
sebelipase alfa (0.35 mg/kg, 1.0 mg/kg, or 3.0 mg/kg) and then transitioned to
every other week infusions of sebelipase alfa (1.0 mg/kg or 3.0 mg/kg). Eight
of nine patients have enrolled in the extension study. Data at the AASLD
meeting were derived from the seven of the eight patients who completed the
first six months of dosing in the extension study.

Patients in the Phase I/II trial were predominantly male with a mean age of 32
years (range 19-45). Seven of nine patients had a history of hepatomegaly
and/or splenomegaly, and two of nine patients had evidence of more advanced
liver disease, including cirrhosis and portal hypertension. Seven patients had
a history of other cardiovascular conditions. Seven of nine patients were
receiving treatment with lipid modifying therapies including ezetimibe,
statins, and other medications.

For the seven patients with longer term dosing, sebelipase alfa produced mean
decreases +/- SD for ALT and AST from the initial baseline to week 24 of the
extension study of 48 +/- 21 U/L (54%) and 19 +/- 18 U/L (30%), respectively
(p<0.05 for both). In addition, sebelipase alfa resulted in mean decreases
from the initial baseline to week 24 of the extension study for total
cholesterol of 69 +/- 52 mg/dL (31%), LDL-C of 62 +/- 36 mg/dL (43%) and
triglycerides of 47 +/- 69 mg/dL (22%), p<0.05 for all measures, as well as
mean increases in HDL of 4 +/- 5 mg/dL (14%) (p=0.09).

Liver fat fraction was measured by multi-echo magnetic resonance imaging (MRI)
or magnetic resonance spectroscopy (MRS) and liver volume was measured by MRI
at the beginning of the extension study, at weeks 10/12, and at week 24 of the
extension study. Treatment with sebelipase alfa resulted in a mean decrease in
liver fat fraction of 34% and a mean decrease in liver volume of 8% at week
24.

Sebelipase alfa was well tolerated throughout the initial six months of the
extension study. The majority of adverse events were mild and unrelated to
sebelipase alfa. Related or possibly related adverse events included headache,
diarrhea, mild abdominal pain and cholesterol elevation. The majority of
infusion-related reactions were gastrointestinal (diarrhea, abdominal
cramping) and of mild severity. No antidrug antibodies were detected in any of
the nine patients in the four week portion of the trial or in the seven
patients tested in the extension study. A single patient during the extension
study developed acute cholecystitis and cholelithiasis later treated with
cholecystectomy. These two serious adverse events were considered by the
investigator as unlikely related to sebelipase alfa.

Poster 1339 entitled “Enzyme Replacement with Recombinant Human Lysosomal Acid
Lipase (rhLAL) in Patients with Cholesteryl Ester Storage Disease, the Late
Onset Form of LAL Deficiency, Produces Sustained Decreases in Transaminases
and Reduction in Liver Fat Content” can be viewed during the poster session on
Monday, November 12, 2012 at 8:00 a.m.-5:30 p.m. EST.

Additional sebelipase alfa data presented at the AASLD meeting

Poster 1351 entitled “Recombinant Human Lysosomal Acid Lipase Decreases
Hepatic Macrophage Aggregates and Colocalized Fibrosis in a Rat Model of
Lysosomal Acid Lipase Deficiency” can be viewed during the poster session on
Monday, November 12, 2012 at 8:00 a.m.-5:30 p.m. EST. The aim of this study
was to further characterize the histopathological abnormalities associated
with LAL Deficiency and to examine the effects of sebelipase alfa on liver
fibrosis in the preclinical rat model. In this study, enzyme replacement with
sebelipase alfa was associated with a marked reduction of fat in disease
causing cells including macrophages and hepatocytes with an accompanying
reduction in fibrosis relative to untreated LAL deficient animals.

About Synageva’s Lead Program

Sebelipase alfa is a recombinant form of the human LAL enzyme under
development by Synageva as an enzyme replacement therapy for LAL Deficiency, a
lysosomal storage disorder (LSD). Synageva is currently evaluating sebelipase
alfa in global clinical trials and sebelipase alfa has been granted orphan
designations by the U.S. Food and Drug Administration (FDA), the European
Medicines Agency, and the Japanese Ministry of Health, Labour and Welfare.
Additionally, sebelipase alfa received “fast track” designation by the FDA.

About LAL Deficiency

LAL Deficiency is a rare, autosomal recessive LSD caused by a marked decrease
in LAL enzyme activity. Late onset LAL Deficiency, sometimes called
Cholesteryl Ester Storage Disease (CESD), affects both children and adults. In
these patients, the buildup of fatty material in the liver, spleen and blood
vessel walls leads to complications resulting in significant morbidity and
mortality. Early onset LAL Deficiency, sometimes called Wolman disease,
affects infants and is characterized by severe malabsorption, growth failure,
and liver failure and is usually fatal within the first six months of life.

About Synageva BioPharma Corp.

Synageva is a clinical stage biopharmaceutical company focused on the
discovery, development, and anticipated commercialization of therapeutic
products for patients with life-threatening rare diseases and unmet medical
need. Synageva has several protein therapeutics in its drug development
pipeline. The company has assembled a team with a proven record of bringing
therapies to patients with rare diseases.

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

Forward-Looking Statements

This news release contains “forward-looking statements” under the provisions
of the Private Securities Litigation Reform Act of 1995. Such statements can
be identified by introductory words such as “expects,” “plans,” “intends,”
“believes,” “will,” “estimates,” “forecasts,” “projects,” or words of similar
meaning and by the fact that they do not relate strictly to historical or
current facts. Many factors may cause actual results to differ materially from
forward-looking statements, including inaccurate assumptions and a broad
variety of risks and uncertainties, some of which are known, including those
identified under the heading “Risk Factors” in the Company’s Quarterly Report
on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on
November 6, 2012, and other filings Synageva periodically makes with the SEC
and others of which are not. Synageva cannot be sure when or if it will be
permitted by regulatory agencies to undertake additional clinical trials or to
commence any particular phase of clinical trials or how quickly patient
enrollment in clinical trials will occur. In addition, early clinical results
are not necessarily predictive of results that may be achieved from subsequent
clinical trials. Because of this, statements regarding the expected timing of
clinical trials or ultimate regulatory approval cannot be regarded as actual
predictions of when Synageva will obtain regulatory approval for any phase of
clinical trials or when it will obtain ultimate regulatory approval by a
particular regulatory agency or when any of its drug product candidates might
be commercialized. Synageva’s future financial results may differ from those
currently anticipated due to a number of factors, including unanticipated
costs in its research and development programs, fluctuations in royalty
revenues and unplanned costs associated with maintaining and enforcing patents
and other patent-related costs. 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.

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

Contact:

Synageva BioPharma Corp.
Matthew Osborne, 781-357-9947
matthew.osborne@synageva.com
 
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