Clear Biologic Activity, Tolerability and Trends Toward Efficacy Observed

    SEATTLE, Washington and GENEVA, Switzerland, November 13
/PRNewswire-FirstCall/ -- ZymoGenetics, Inc. (NASDAQ: ZGEN) and Serono
(virt-x: SEO and NYSE: SRA) today presented positive results at the
American College of Rheumatology (ACR) annual meeting from a Phase 1b study
in systemic lupus erythematosus (SLE) patients treated with atacicept[1].
The results showed that atacicept was well tolerated across all dose levels
and schedules in the study. In addition, atacicept therapy was associated
with clear biologic activity, as shown by dose-dependent reductions in
several biologic markers, consistent with atacicept's proposed mechanism of
action.
    "ZymoGenetics and Serono are striving to develop an effective therapy
for patients who suffer from lupus," said Bruce L.A. Carter, President and
Chief Executive Officer of ZymoGenetics. "We believe atacicept has the
potential to help people with this debilitating disease."
    The primary objective of the dose-escalating Phase 1b clinical trial,
which included 49 patients with SLE in 6 cohorts, was to determine the
safety and tolerability of atacicept administered subcutaneously. Secondary
objectives included examining the effects of various dose and schedule
regimens on markers of biologic activity and disease activity.
    "The Phase 1b results are very encouraging and we are looking forward
to moving the clinical development of atacicept in patients with SLE to
Phase 2," said Franck Latrille, Senior Executive Vice President, Corporate
Global Product Development at Serono.
    ZymoGenetics and Serono are in dialogue with the FDA regarding the SLE
Phase 2 clinical development program. The companies are planning to
initiate the trial in SLE in mid-2007.
    Key Study Findings:
    Clear biologic activity:
    Consistent with the mode of action:
    - Immunoglobulins showed prompt dose-related decreases with atacicept
treatment.
    - Among patients treated with the highest study dose of atacicept
(9mg/kg), median IgA, IgG and IgM levels were reduced by 32, 16 and nearly
50 percent relative to baseline. Patients treated with placebo showed
average reductions of only four percent.
    - Repeated doses were associated with greater decreases in
immunoglobulin (Ig) levels than single equivalent doses.
    - Following treatment cessation, Ig levels returned towards baseline.
    - Mature and total B-cells showed a sustained, dose-related reduction.
    Tolerability:
    - No serious adverse events were reported in patients treated with
atacicept.
    - There was no evidence of increased infection risk among treated
subjects, and no binding antibodies to atacicept were detected.
    Positive trend towards efficacy:
    - Although the study was not designed to evaluate efficacy, compared to
placebo an overall positive trend in SELENA-SLEDAI scores[2] and complement
levels was seen in patients treated with multiple doses of atacicept.
    A separate poster[3] presented at ACR reviewed findings from a Phase 1b
study with atacicept in patients with rheumatoid arthritis, as announced
earlier this year. The companies are planning to initiate the Phase 2 study
with atacicept in RA patients before the end of 2006.
    About the Study
    The double blind, placebo-controlled, dose escalating, multi-site Phase
1b trial enrolled forty-nine patients with mild-to-moderate SLE. Six
cohorts, consisting of eight patients each, were treated with either
atacicept or placebo. Cohorts 1 through 4 received a single subcutaneous
dose of 0.3, 1, 3, or 9 mg/kg of atacicept respectively. Cohorts 5 and 6
received four weekly doses of 1 mg/kg or 3 mg/kg respectively. Patients
were followed for either six weeks (cohorts 1-4) or nine weeks (cohorts
5-6). All patients were monitored during and for several weeks after dosing
for safety purposes.
    The primary outcome measure was the systemic and local tolerability of
atacicept administered subcutaneously. The secondary measures included
pharmacokinetics and pharmacodynamics, as well as measures of SLE disease
activity.
    Atacicept was well tolerated by patients with SLE at all doses
investigated. There was a clear demonstration of biologic activity
consistent with the mechanism of action of atacicept and positive trends
towards efficacy were observed.
    Overall, the results demonstrated a favorable tolerability profile. The
predominant adverse event noted was a mild to moderate local injection site
reaction (redness of skin or pain at the injection site), which was
observed in 50% of atacicept subjects and less frequently in the placebo
and 0.3 mg/kg groups. Few notable differences were observed between
atacicept and placebo in the nature, severity or frequency of adverse
events.
    About Atacicept
    ZymoGenetics and Serono are developing atacicept (formerly referred to
as TACI-Ig) for the treatment of autoimmune diseases and B-cell
malignancies. Atacicept contains the soluble TACI receptor that binds to
the cytokines BLyS and APRIL. These cytokines, in turn, are members of the
tumor necrosis factor (TNF) family that promote B-cell survival and
autoantibody production associated with certain autoimmune diseases such as
systemic lupus erythematosus (SLE). Current data indicates that levels of
BLyS and APRIL are elevated in patients with rheumatoid arthritis, SLE and
B-cell malignancies. Atacicept has been shown to affect several stages of
B-cell development and may inhibit the survival of cells responsible for
making antibodies.
    Posters
    The abstracts and posters are available at http://www.zymogenetics.com in the
'What's New' section on the home page.
    Background material
    For free B-roll, video and other content for Serono and its products,
please visit the Serono Media Center http://www.thenewsmarket.com/Serono. You can
download print-quality images and receive broadcast-standard video
digitally or by tape from this site. Registration and video is free to the
media.
    Forward-looking Statements
    For ZymoGenetics
    This press release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995. These
forward-looking statements are based on the current intent and expectations
of the management of ZymoGenetics. These statements are not guarantees of
future performance and involve risks and uncertainties that are difficult
to predict. ZymoGenetics' actual results and the timing and outcome of
events may differ materially from those expressed in or implied by the
forward-looking statements because of risks associated with our unproven
discovery strategy, preclinical and clinical development, regulatory
oversight, intellectual property claims and litigation and other risks
detailed in the company's public filings with the Securities and Exchange
Commission, including the company's Annual Report on Form 10-K for the year
ended December 31, 2005. Except as required by law, ZymoGenetics undertakes
no obligation to update any forward-looking or other statements in this
press release, whether as a result of new information, future events or
otherwise.
    For Serono
    Some of the statements in this press release are forward looking. Such
statements are inherently subject to known and unknown risks, uncertainties
and other factors that may cause actual results, performance or
achievements of Serono S.A. and affiliates to be materially different from
those expected or anticipated in the forward-looking statements.
Forward-looking statements are based on Serono's current expectations and
assumptions, which may be affected by a number of factors, including those
discussed in this press release and more fully described in Serono's Annual
Report on Form 20-F filed with the U.S. Securities and Exchange Commission
on February 28, 2006. These factors include any failure or delay in
Serono's ability to develop new products, any failure to receive
anticipated regulatory approvals, any problems in commercializing current
products as a result of competition or other factors, our ability to obtain
reimbursement coverage for our products, the outcome of government
investigations and litigation and government regulations limiting our
ability to sell our products. Serono has no responsibility to update the
forward-looking statements contained in this press release to reflect
events or circumstances occurring after the date of this press release.
    About ZymoGenetics
    ZymoGenetics creates novel protein drugs with the potential to
significantly help patients fight their diseases. The Company is developing
a diverse pipeline of potential proprietary product candidates that are
moving into and through clinical development. These candidates span a wide
array of clinical opportunities that include bleeding, autoimmune diseases
and cancer. ZymoGenetics intends to commercialize these product candidates
through internal development, collaborations with partners, and
out-licensing of patents from its extensive patent portfolio. For further
information, visit http://www.zymogenetics.com.
    About Serono
    Serono is a global biotechnology leader. The Company has eight
biotechnology products, Rebif(R), Gonal-f(R), Luveris(R), Ovidrel(R
)/Ovitrelle(R), Serostim(R), Saizen(R), Zorbtive(TM) and Raptiva(R). In
addition to being the world leader in reproductive health, Serono has
strong market positions in neurology, metabolism and growth and has
recently entered the psoriasis area. The Company's research programs are
focused on growing these businesses and on establishing new therapeutic
areas, including oncology and autoimmune diseases.
    In 2005, Serono, whose products are sold in over 90 countries, achieved
worldwide revenues of US$2,586.4 million. Reported net loss in 2005 was
US$106.1 million, reflecting a charge of US$725 million taken relating to
the settlement of the US Attorney's Office investigation of Serostim.
Excluding this charge as well as other non-recurring items, adjusted net
income grew 28.4% to US$565.3 million in 2005. Bearer shares of Serono
S.A., the holding company, are traded on the virt-x (SEO) and its American
Depositary Shares are traded on the New York Stock Exchange (SRA).
    [1] Trial of Atacicept in Patients with Systemic Lupus Erythematosus
(SLE) (poster L19/499), ACR/ARHP Poster Session B Late-Breaking Posters,
November 13, 2006, American College of Rheumatology Annual Meeting
    [2] SELENA-SLEDAI: SLE Disease Activity Index; The original SLEDAI is a
weighted, cumulative index of lupus disease activity, and the SELENA SLEDAI
represents a further refinement.
    [3] A Phase Ib Study to Investigate Atacicept (TACI-Ig) In Patients
With Rheumatoid Arthritis (poster L36/516). ACR/ARHP Poster Session B
Late-Breaking Posters, November 13, 2006, American College of Rheumatology
Annual Meeting

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