Vical Announces Breakthrough For Pandemic Influenza DNA Vaccines With Preliminary Human Data

Vical Incorporated
(Nasdaq: VICL) announced a breakthrough with preliminary clinical
trial data demonstrating that DNA vaccines can safely achieve significant
immune responses against H5N1 pandemic influenza in humans. DNA vaccines
are fundamentally different from conventional vaccines because they do not
contain any part of the virus itself, and may offer compelling advantages
in response to a pandemic outbreak because of significantly reduced
development and manufacturing times.



Specifically, preliminary human safety and immunogenicity data obtained
in a 100-subject Phase 1 trial of the company's Vaxfectin(R)-formulated
H5N1 pandemic influenza DNA vaccines demonstrated for the first time that
DNA vaccines have achieved potentially protective levels of antibody
responses (defined as hemagglutination inhibition, or HI, titers of at
least 40; responses ranged from 40 to 640) in up to 67% of evaluable
subjects in the higher dose cohorts. No significant safety issues were
observed at any of the Vical vaccine doses tested. These results support
further development of Vaxfectin(R)-formulated DNA vaccines, and could
position them as potential alternatives to conventional vaccines.



"The preliminary results from this Phase 1 trial indicate for the first
time that an adjuvanted DNA vaccination against H5N1 influenza is
well-tolerated and can induce impressive antibody responses even against
this relatively weak immunogen," said Robert B. Belshe, M.D., Dianna and J.
Joseph Adorjan Endowed Professor of Infectious Diseases and Immunology,
Saint Louis University School of Medicine, who was the lead external safety
monitor for the study. "Successful development of a safe and effective DNA
vaccine will help address the potential public health threat of pandemic
influenza."



Vijay B. Samant, Vical's President and Chief Executive Officer, said,
"Our preliminary Phase 1 pandemic influenza vaccine results clearly
demonstrate the potential of Vaxfectin(R)-formulated DNA vaccines to
achieve antibody responses in the same range as conventional vaccines. The
ability to manufacture DNA vaccines in weeks rather than the months
required for conventional vaccines may provide a significant advantage when
dealing with an emerging infectious disease such as pandemic influenza.
This trial is also important because it marks the first successful safety
evaluation in humans for our Vaxfectin(R) adjuvant, which has potential
applications with both DNA vaccines and conventional protein-based
vaccines."



The double-blind, placebo-controlled, dose-escalation trial was
conducted in approximately 100 healthy volunteers age 18 to 45 at three
U.S. clinical sites. The trial was designed to assess safety and
immunogenicity following intramuscular vaccination with needle and syringe
or with the Biojector(R) 2000 needle-free injection system in different
cohorts, and to evaluate monovalent and trivalent Vaxfectin(R)-formulated
DNA vaccines at various doses. Preliminary results will be presented by
Vical's Vice President of Vaccine Research, Larry R. Smith, Ph.D., at 12:25
p.m. EDT today, Thursday, July 17, at the IBC Life Sciences Next Generation
Vaccines conference (National Harbor, MD - July 17-18).
















In the Phase 1 trial, subjects were injected at Days 0 and 21. Primary
evaluation of antibody responses was by HI antibody titers, the accepted
standard correlate of protection for influenza vaccines. Responders were
those subjects achieving H5 HI titers of at least 40 and achieving at least
a four-fold increase from baseline HI titers. By Day 56, at least 50% and
up to 67% of evaluable subjects were responders in each of the three
cohorts receiving 0.5 mg or 1 mg H5 DNA doses, and there were no responders
in the placebo cohort. More than 90% of the responders had sustained HI
titers through the last measurement to date (Day 84). Neutralizing antibody
production against H5 was demonstrated separately by microneutralization
assays. For comparison, the protein-based pandemic influenza vaccine
currently stockpiled by the U.S. government was approved with HI titers of
40 or more in 44% of subjects by Day 56.



Even at the lowest dose tested (0.033 mg H5 DNA), one of the six
subjects was a responder by Day 56. Some subjects who received the highest
H5 DNA dose were responders at Day 21 after a single vaccine injection.
Preliminary analyses also showed cross-strain immune responses against a
strain of H5N1 from a clade not matching the vaccine. Cross-strain
protection could be important against emerging strains of pandemic
influenza that may not match vaccine stockpiles.



Additional assays are ongoing to further evaluate antibody responses,
breadth and magnitude of T-cell immune responses, cross-strain responses,
and the relative advantages of monovalent vs. trivalent vaccines and needle
vs. needle-free injection.



"These results are important to Vical for three reasons," added Mr.
Samant. "First, they encourage further development of pandemic influenza
DNA vaccines, for which we are currently exploring funding or partnering
options. Second, they support advancement of additional
Vaxfectin(R)-formulated DNA vaccines toward clinical testing. Third, they
provide new incentives for potential commercial partners and collaborators
to explore additional applications for our Vaxfectin(R) adjuvant for DNA
vaccines as well as protein and peptide-based vaccines. We are excited by
these strong preliminary antibody results, and we look forward to
evaluating more detailed immunogenicity data as they become available."



DNA vaccines may offer both technical and economic advantages compared
with conventional vaccine approaches. DNA vaccines encode certain proteins
associated with a target pathogen, rather than using any part of the
pathogen itself, and can prime the immune system as well as induce potent
antibody and T-cell immune responses. DNA vaccines contain no viral
particles, are non-infectious, and can be administered on a repeat basis
without unwanted immune responses. Additionally, DNA vaccines have the
potential to achieve proof of concept more quickly and cost-effectively
than conventional vaccines, and can be manufactured using uniform methods
of fermentation and purification, allowing significantly faster development
and production.



Vical's monovalent vaccine contains a plasmid (a closed loop of DNA)
encoding the hemagglutinin (HA) surface protein from the H5N1 influenza
virus strain, A/Vietnam/1203/04. It is designed primarily to elicit
antibody responses against the H5 protein but could elicit T-cell responses
against H5 as well. Vical's trivalent vaccine contains the H5 plasmid plus
separate plasmids encoding consensus sequences of two highly conserved
influenza virus proteins: nucleoprotein (NP) and ion channel protein (M2).
The trivalent vaccine is designed to elicit a combination of T-cell and
antibody responses against all three proteins. Both vaccines are formulated
with the company's Vaxfectin(R) adjuvant, which has demonstrated
effectiveness with a variety of DNA vaccines in multiple animal models as
well as dose-sparing and immune-enhancing ability in animals with a
conventional seasonal influenza vaccine.



About Vical



Vical researches and develops biopharmaceutical products based on its
patented DNA delivery technologies for the prevention and treatment of
serious or life-threatening diseases. Potential applications of the
company's DNA delivery technology include DNA vaccines for infectious
diseases or cancer, in which the expressed protein is an immunogen; cancer
immunotherapeutics, in which the expressed protein is an immune system
stimulant; and cardiovascular therapies, in which the expressed protein is
an angiogenic growth factor. The company is developing certain infectious
disease vaccines and cancer therapeutics internally. In addition, the
company collaborates with major pharmaceutical companies and biotechnology
companies that give it access to complementary technologies or greater
resources. These strategic partnerships provide the company with mutually
beneficial opportunities to expand its product pipeline and address
significant unmet medical needs. Additional information on Vical is
available at vical.



This press release contains forward-looking statements subject to risks
and uncertainties that could cause actual results to differ materially from
those projected. Forward-looking statements include statements about the
preliminary results of the company's DNA vaccine Phase 1 clinical trial,
the effect of the preliminary Phase 1 clinical trial results on the
company's DNA vaccine and Vaxfectin(R) adjuvant programs and its
collaborative opportunities, and the design and potential benefits of the
company's pandemic influenza vaccine and DNA vaccines generally. Risks and
uncertainties include whether preliminary H5N1 DNA vaccine Phase 1 clinical
trial results will be confirmed upon further analysis or in larger studies;
whether DNA vaccines against H5N1 influenza or any other targets will be
successfully developed and commercialized; whether DNA vaccines will become
alternatives to conventional vaccines; whether DNA vaccines will achieve
immune responses in the same range as conventional vaccines in future
trials; whether infrastructure will be established to manufacture DNA
vaccines at commercial scale in weeks; whether additional data will provide
evidence of neutralizing antibody production, cross-strain immune
responses, or T-cell responses; whether further analysis will reveal any
advantages for the monovalent or trivalent vaccines or for the needle or
needle-free injection methods; whether Vical or others will secure funding
to advance the pandemic influenza DNA vaccine program; whether commercial
partners or collaborators will pursue additional Vaxfectin(R) applications;
whether any product candidates will be shown to be safe and efficacious in
clinical trials; the timing of clinical trials; whether Vical or its
collaborative partners will seek or gain approval to market any product
candidates; the dependence of the company on its collaborative partners;
and additional risks set forth in the company's filings with the Securities
and Exchange Commission. These forward-looking statements represent the
company's judgment as of the date of this release. The company disclaims,
however, any intent or obligation to update these forward-looking
statements.


Vical Incorporated

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