| December
20, 2004
Dynavax Announces Interim Analysis
From Ragweed Allergy Phase 2/3 Trial
Positive Trends Relative to Primary
and Secondary Endpoints Demonstrated
BERKELEY, Calif., Dec. 20 /PRNewswire-FirstCall/
-- Dynavax Technologies (Nasdaq: DVAX)
announced that the one-year interim
analysis of the company's two-year
Phase 2/3 clinical trial of its ragweed
allergy ISS-based therapeutic (AIC,
or Amb a 1 ISS conjugate) showed a
clear positive trend relative to the
trial's major endpoint of nasal symptom
scores, as well as other secondary
endpoints, following the 2004 ragweed
season. The interim analysis indicated
that AIC was safely administered and
systemic adverse reactions were similar
between the AIC and control arms.
Dynavax intends to complete the two-year
clinical trial as planned, a decision
that was endorsed by an independent
Drug Safety Monitoring Board. Manufacturing
of the Phase 3 clinical supply of
AIC will also be completed. The ongoing
462-patient Phase 2/3 clinical trial,
which was initiated in early 2004
and whose primary endpoint is the
reduction of nasal symptom scores
during the summer/fall 2005 ragweed
season, will remain blinded until
those data are collected and fully
analyzed.
Pending the outcome of discussions
with the US Food and Drug Administration
(FDA) in early 2005, Dynavax will
determine the design, target populations
and timing of initiating a pivotal
Phase 3 clinical program, now expected
to begin in 2006. In addition, Dynavax
will discuss with the FDA plans to
initiate a supportive Phase 3 trial
in a pediatric indication in 2005.
"We believe that the positive
trends shown in the AIC Phase 2/3
interim analysis suggest a therapeutic
benefit and we are optimistic that
the benefit will last, and potentially
increase, through the second season,"
said Dino Dina, MD, president and
chief executive officer. "This
promising outcome, combined with recently
reported positive Phase 2/3 interim
clinical results with our hepatitis
B vaccine, support the clinical rationale
for pursuing ISS- based approaches
in other allergies such as grass,
peanut and cedar, as well as in inflammatory
and viral diseases. We believe that
our AIC therapy has the potential
to provide an important therapeutic
alternative for hay fever sufferers
and could become a significant commercial
opportunity for Dynavax. We look forward
to upcoming discussions with the FDA
concerning timing and scope of a Phase
3 AIC clinical program."
In February 2004, Dynavax and UCB
Pharma established a strategic partnering
agreement for development and commercialization
of seasonal allergy products. Dynavax
understands that UCB is reviewing
its commitment to the program. Should
UCB Pharma opt to exercise its contractual
right to return the allergy program
to Dynavax, Dynavax is planning to
pursue the ongoing development of
AIC independently.
Design of the Phase 2/3 Clinical
Trial
Over the last several years, Dynavax
has generated a substantial amount
of clinical data on AIC. AIC has been
tested in 14 clinical trials in the
U.S., France, and Canada, and more
than 3,000 AIC injections have been
administered to over 500 ragweed allergic
people. Data from earlier trials have
shown AIC to be safe and well tolerated,
to provide improvements in allergy
symptoms, and to reduce medication
use.
The ongoing Phase 2/3 AIC clinical
trial, initiated in the first quarter
of 2004, is a two-year, double-blind,
placebo-controlled study being conducted
at 29 sites in the midwestern, southwestern
and eastern US. The trial involves
462 subjects with moderate to severe
ragweed allergy (hay fever). Prior
to the 2004 ragweed season, which
generally lasts from August through
October, subjects received six weekly
doses of either placebo or escalating
doses of up to 30 micrograms of AIC,
in a two-to-one randomization, AIC
to placebo group. Prior to the 2005
ragweed season, one half of the AIC-treated
subjects will receive two additional
booster shots. The other half of the
AIC-treated group will receive placebo
injections and the original placebo-treated
group will receive placebo injections.
The primary endpoint of this trial
is the change in the total nasal symptom
score following the 2005 ragweed season.
Secondary endpoints include reduction
in medication usage and improvement
in quality of life scores. The design
of the trial should also permit comparison
of the AIC- treated groups with and
without the booster dose.
The blinded interim analysis was
conducted following the first year
ragweed season with the goal of providing
a basis for determining the timing
and scope of the Phase 3 clinical
program. The actual design of the
Phase 3 program is under review and
is anticipated to include an early
intervention trial in children designed
to prevent allergic rhinitis and progression
to asthma.
About ISS and Allergy
ISS are short synthetic DNA molecules
that stimulate a Th1 immune response
while suppressing Th2 immune responses.
ISS contain specific sequences that
activate the innate immune system.
ISS are recognized by a specialized
subset of dendritic cells containing
a unique receptor called Toll-Like
Receptor 9, or TLR-9. The interaction
of TLR-9 with ISS triggers the biological
events that lead to the suppression
of the Th2 immune response and the
enhancement of the Th1 immune response.
ISS influence helper T cell responses
in a targeted and highly specific
way by redirecting the response of
only those T cells involved in a given
disease. ISS, in conjunction with
an allergen or antigen, establish
populations of memory Th1 cells, allowing
the immune system to respond appropriately
to each future encounter with a specific
pathogen or allergen, leading to long-lasting
therapeutic effects.
AIC consists of 1018 ISS linked to
the purified major allergen of ragweed,
called Amb a 1. AIC targets the underlying
cause of seasonal allergic rhinitis
induced by ragweed pollen. The linking
of ISS to Amb a 1 is designed to ensure
that both ISS and ragweed allergen
are presented simultaneously to the
same immune cells, with the goal of
producing a highly specific and potent
inhibitory effect and suppressing
the Th2 cells responsible for inflammation
associated with ragweed allergy. This
treatment is intended to reprogram
the immune response away from the
Th2 response and toward a Th1 memory
response so that, upon subsequent
natural exposure to the ragweed allergen,
long-term immunity can be achieved.
Potential AIC Commercial Opportunity
Medical management of seasonal allergic
rhinitis is a multibillion-dollar
global market. In the U.S. alone,
approximately 40 million people suffer
from allergic rhinitis. Ragweed is
the single most common seasonal allergen,
affecting up to 75% of those with
allergic rhinitis, or 30 million Americans.
The direct costs of prescription and
over-the-counter interventions for
allergic rhinitis in the U.S. are
estimated to exceed $7 billion. In
addition, 20-30% of those who suffer
from allergic rhinitis progress to
asthma, leading to increased morbidity
and disease management costs. Dynavax
believes that a significant market
opportunity exists for AIC in the
treatment of ragweed allergic individuals
currently undergoing conventional
immunotherapy or using multiple prescription
or OTC medications. In addition, the
product may also play a role in earlier
stage disease, potentially preventing
the "allergic march" from
allergic rhinitis to asthma.
Dynavax will hold a conference call
to discuss its AIC clinical program
today at 10:00 a.m. Eastern Time.
Interested parties may listen to the
webcast live at http://www.dynavax.com
. The webcast is also being distributed
over CCBN's Investor Distribution
Network to both institutional and
individual investors. Individual investors
can listen to the call through CCBN's
individual investor center at http://www.fulldisclosure.com
or by visiting any of the investor
sites in CCBN's Individual Investor
Network. Institutional investors can
access the call via CCBN's password-protected
event management site, StreetEvents,
at http://www.streetevents.com . A
telephonic replay will be available
through December 28, 2004 by dialing
888-286-8010, conference identification
number 54830688. International callers
can dial 617-801-6888, conference
identification number 54830688.
About
Dynavax Technologies Dynavax Technologies
is a privately held biopharmaceutical
company developing innovative products
to treat allergy, inflammation-mediated
diseases, infectious diseases and
cancer. The companys lead products
are based on ImmunoStimulatory Sequences
(ISS), short DNA sequences that enhance
the ability of the immune system to
fight disease and prevent inflammation.
The companys two most advanced
products are AIC, which has provided
positive results in recently completed
phase II clinical trials for the treatment
of ragweed allergy, and a next-generation
hepatitis B vaccine that may offer
single-dose protection. Dynavax is
also developing an oral TNF-alpha
synthesis inhibitor initially for
the treatment of rheumatoid arthritis.
The company has collaborations with
Aventis-Pasteur, Triangle Pharmaceuticals
and Stallergenes.
Contact:
Andrew Gengos Chief Financial Officer
Dynavax Technologies Corporation (510)
848-5100
Note: This press
release contains "forward looking
statements" within the meaning
of the federal securities laws. These
forward-looking statements include
without limitation, statements relating
to the potential success of product
development, subsequent regulatory
approvals and potential product sales.
These statements are subject to risks
and uncertainties that could cause
actual results and events to differ
materially from those anticipated.
Readers are cautioned not to place
undue reliance on these forward-looking
statements that speak only as of the
date of this release. Dynavax undertakes
no obligation to update publicly any
forward-looking statements to reflect
new information, events or circumstances
after the date of this release except
as required by law.
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