Alexza's AZ-004 (Staccato(R) Loxapine) Phase 3 Trial Meets Primary Endpoint of Treating...

Alexza's AZ-004 (Staccato(R) Loxapine) Phase 3 Trial Meets Primary Endpoint of
Treating Acute Agitation in Schizophrenic Patients
Conference Call Scheduled for Today - Tuesday, September 2, 2008 at 5:00 p.m.
Eastern Time

MOUNTAIN VIEW, Calif., Sept. 2 /PRNewswire-FirstCall/ -- Alexza
Pharmaceuticals, Inc. (Nasdaq: ALXA) today announced positive results from
its first Phase 3 clinical trial of AZ-004 (Staccato(R) loxapine) in
schizophrenic patients with acute agitation. Both the 5 mg and 10 mg doses of
AZ-004 met the primary endpoint of the trial, which was a statistically
significant reduction in agitation from baseline to the 2-hour post-dose time
point, compared to placebo. AZ-004 is an inhalation product candidate being
developed for the treatment of acute agitation in patients with schizophrenia
or bipolar disorder. AZ-004 is being developed through Symphony Allegro, a
product development partnership formed between Alexza and Symphony Capital,
LLC.
"Alexza initiated the first Phase 3 clinical trial of our lead program in
late February and completed enrollment in less than four months, and today we
are reporting positive top-line results for the primary and secondary
endpoints," said James V. Cassella, PhD, Alexza Senior Vice President,
Research and Development. "We believe that the ability to provide loxapine
via our Staccato technology, thus combining a drug with a well-established
mechanism of action with rapid absorption and patient self-administration,
makes AZ-004 a potentially important new drug candidate for treating acute
agitation."
"The clinical data we have seen to date, in terms of both efficacy and
side-effect profiles, are compelling," said Michael H. Allen, MD, Director of
Research, University of Colorado Depression Center. "There is a significant
unmet medical need to treat acute agitation with new therapies that provide
rapid onset of predictable effect and are delivered in a patient-friendly,
non-invasive manner."
Phase 3 Clinical Trial Design
The AZ-004 clinical trial enrolled 344 schizophrenic patients with acute
agitation at 24 U.S. clinical centers. The trial was designed as an
in-clinic, multi-center, randomized, double-blind, placebo-controlled study
and tested AZ-004 at two dose levels, 5 mg and 10 mg. Patients were eligible
to receive up to 3 doses of study drug in a 24-hour period, depending on their
clinical status. Only one dose of study drug was allowed during the first 2
hours of the study period.
The primary endpoint for the study was the change from baseline in the
PANSS (Positive and Negative Symptom Scale) Excited Component score (also
known as PEC score), measured at 2 hours after the first dose. The key
secondary endpoint was the Clinical Global Impression-Improvement (CGI-I)
score, measured at 2 hours after the first dose. All results were considered
statistically significant at the p < 0.05 level, as compared to placebo, and
all analyses were made on an intent-to-treat basis. Various additional
assessments of a patient's agitation state were conducted at serial time
points using the PEC scale over the first 4-hour post-dose time period, with
follow-up assessments at the end of the 24-hour study period. Side effects
were recorded for each patient throughout their 24-hour study period.
Primary Efficacy Endpoint
Both the 5 mg and the 10 mg dose of AZ-004 met the primary endpoint of the
clinical trial, showing a statistically significant improvement in the 2-hour
post-dose PEC score, compared to placebo.
PEC Scores (Mean Values)

p-Value for Change
from Baseline
Study Arm Baseline 2-Hour Post-Dose vs. Placebo
10 mg AZ-004
(n=112) 17.6 9.0 < 0.0001
5 mg AZ-004
(n=116) 17.8 9.8 0.0004
Placebo
(n=115) 17.4 11.8 -

Key Secondary Efficacy Endpoint
A Clinical Global Impression-Severity (CGI-S) scale rating of agitation
was completed at baseline for each patient, prior to AZ-004 administration, to
ensure comparability across groups. The CGI-S scale ranges from 1 (normal) to
7 (among the most extremely agitated patients). Scores were similar across
the three dose groups with a range of 3.9 to 4.1.
In addition to the PEC score, the Clinical Global Impression-Improvement
(CGI-I) is another commonly used scale to measure the reduction of agitation
in patients over time, normally following therapeutic treatment. The CGI-I
standard scale ranges from 1 (very much improved) to 7 (very much worse). At
the 2-hour post-dose time point, a CGI-I scale rating was completed for each
patient, which was the key secondary endpoint of the study. Both the 10 mg
and the 5 mg doses of AZ-004 showed statistically significant differences
versus placebo in the CGI-I scores at the 2-hour post-dose time point.
CGI-I Scores (Mean Values)

Study Arm 2-Hour Post-Dose p-Value
10 mg AZ-004 (n=112) 2.1 < 0.0001
5 mg AZ-004 (n=115) 2.3 0.0015
Placebo (n=115) 2.8 -

Additional Efficacy Endpoints
The 10 mg dose of AZ-004 also exhibited a rapid onset of effect. At 10
minutes post-dose, the 10 mg dose showed a statistically significant
improvement in the PEC score (p < 0.0001), compared to placebo. The 10 mg
dose sustained this statistically significant improvement at all measurement
time points throughout the 24-hour study period, compared to placebo. The 5
mg dose was not statistically tested at the time points other than the 2-hour
time point, as per the statistical analysis plan, but the mean changes in PEC
scores demonstrated a dose response at all time points.
A dose response pattern for AZ-004 was also apparent, as measured by the
need for a patient to require more than one dose of study drug by the 4-hour
post-first dose time point. Compared to the 44% of the placebo group that
required more than one dose of the study drug, only 25% of the 10 mg group
(p = 0.0039) and 32% of the 5 mg group (p = 0.085) required more than one dose
of study drug.
A responder analysis was conducted using the CGI-I scale. A responder was
defined as having a CGI-I score at 2 hours after the first dose of either a 1
(very much improved) or 2 (much improved). Both the 5 mg (57% responders; p =
0.0015) and 10 mg (67% responders; p < 0.0001) doses of AZ-004 were
statistically superior to placebo (36% responders).
Safety Evaluations
Side effects were recorded throughout the clinical trial period. The
administration of AZ-004 was generally safe and well tolerated. The most
common side effects reported (> 10% in any treatment group) were taste
(dysgeusia), dizziness, sedation and headache. These side effects were
generally mild to moderate in severity, and occurred in both drug and placebo
dose groups.

Treatment Emergent Side Effects
(> 2% in any treatment group)

Placebo 5 mg AZ-004 10 mg AZ-004
Term (n=115) (n=116) (n=113)
Dysgeusia 3 % 9 % 11 %
Dizziness 10 % 5 % 11 %
Sedation 10 % 13 % 11 %
Oral
Hypoaesthesia 0 % 1 % 4 %
Headache 14 % 3 % 3 %
Somnolence 3 % 3 % 3 %
Nausea 5 % 1 % 2 %
Vomiting 3 % 1 % 1 %
Agitation 3 % 1 % 0 %

There were two serious adverse events reported during the trial:
exacerbation of schizophrenia (1 patient in the placebo group) and
gastroenteritis (1 patient in the 10 mg group). Both of these events were
scored by the investigator as "unrelated" to study drug.
The Agitation-Calmness Evaluation Scale (ACES) was recorded at baseline
and at 2 hours after dosing, to determine the level of patient sedation.
Baseline ACES scores were similar across the three patient groups. Mean
scores at 2-hours post-dose for the 5 mg and 10 mg AZ-004 groups were in the
range of "normal" to "mild calmness".
"These positive Phase 3 results, corroborating our Phase 2 findings, show
that AZ-004 is a viable product candidate to treat acute agitation," said
Thomas B. King, Alexza President and CEO. "We are very encouraged with the
pace at which we have developed into a Phase 3 company. In addition to our
clinical successes, we are aggressively escalating many commercialization
activities, including our manufacturing scale-up, quality systems, regulatory
affairs and commercial operations, as we continue to track toward our planned
AZ-004 NDA submission in early 2010."
Conference Call Information
Alexza will host a conference call later today, Tuesday, September 2, 2008
at 5:00 p.m. Eastern Time. A replay of the call will be available for two
weeks following the event. The conference call and replay are open to all
interested parties.
To access the live conference call via phone, dial 800-299-8538.
International callers may access the live call by dialing 617-786-2902. The
reference number to enter the call is 39290605.
The replay of the conference call may be accessed via the Internet, at
http://www.alexza.com, or via phone at 888-286-8010 for domestic callers or
617-801-6888 for international callers. The reference number for the replay
of the call is 52049815.
About Acute Agitation
Acute agitation, characterized by unpleasant arousal, tension,
irritability and hostility, is one of the most common and severe symptoms of
many major psychiatric disorders, including schizophrenia and bipolar
disorder. According to the National Institute of Mental Health (NIMH),
bipolar disorder affects about 5.7 million American adults while schizophrenia
afflicts about 2.4 million people in the United States. Market research among
physicians and health-care providers indicates that over 90% of these patients
will experience agitation during their lifetime and that about 70% of those
who experience agitation will have one to six episodes per year.
Agitated patients are often treated in an emergency department, and are
also treated as in-patients in psychiatric hospitals or psychiatric units in
standard hospitals. Market research among psychiatrists indicates that these
physicians currently treat acute agitation with intramuscular (IM) injections,
rapid-dissolve tablets or standard tablets. IM injections are invasive, can
be disconcerting to patients as they often require the use of restraints, and
can be dangerous to the medical personnel while they attempt to inject the
patient. IM injections can also take up to 60 minutes to work. Oral tablets
provide convenience of dosing alternatives, but have a slower onset of action.
This market research has also identified speed of onset as an important factor
that affects the choice of therapy for treating acute agitation. Alexza
believes that many patients with schizophrenia or bipolar disorder can make
informed decisions regarding their treatment in an acute agitated state and
would prefer a rapid-acting, noninvasive treatment.
In summary, Alexza is developing AZ-004 to potentially offer an acute
agitation treatment option that provides a fast onset of effect, that is
noninvasive and safer to administer than injections, and that allows patients
to be active participants in choosing acceptable treatment options.
About AZ-004 (Staccato loxapine)
AZ-004 is the combination of Alexza's proprietary Staccato system with
loxapine, a drug belonging to the class of compounds known generally as
antipsychotics. The Staccato system is a hand-held, chemically-heated, single
dose inhaler designed to generate and deliver excipient-free drug aerosol for
deep lung delivery that results in IV-like pharmacokinetics. Alexza has
completed four clinical trials with AZ-004 and has announced positive results
from all four studies, including a 50 subject Phase 1 study in healthy
volunteers, a 129 patient Phase 2 study in agitated schizophrenic patients, a
32 patient multiple-dose tolerability and PK study in non-agitated
schizophrenic patients, and a 344 patient Phase 3 study in agitated
schizophrenic patients. In July 2008, Alexza initiated a second Phase 3
clinical trial in bipolar disorder patients with acute agitation.
About Symphony Allegro
In December 2006, Alexza entered into a collaboration with Symphony
Capital LLC, a biotech-focused private equity firm. Under the terms of the
agreement, Alexza and Symphony Capital established Symphony Allegro, Inc.,
which is providing funding to Alexza to accelerate clinical and other related
development activities of Staccato loxapine (AZ-004 and AZ-104) and Staccato
alprazolam (AZ-002). Alexza has granted a license to certain intellectual
property rights for the selected product candidates. Through a purchase
option, Alexza retains the exclusive right, but not the obligation, to acquire
100% of the equity of Symphony Allegro at specified prices during the term of
the agreement. If Alexza chooses not to exercise the purchase option,
Symphony Allegro retains the rights to the product candidates. The purchase
option expires December 1, 2010.
About Alexza Pharmaceuticals, Inc.
Alexza Pharmaceuticals is an emerging specialty pharmaceutical company
focused on the development and commercialization of novel, proprietary
products for the treatment of acute and intermittent conditions. The
Company's technology, the Staccato system, vaporizes unformulated drug to form
a condensation aerosol that allows rapid systemic drug delivery through deep
lung inhalation. The drug is quickly absorbed through the lungs into the
bloodstream, providing speed of therapeutic onset that is comparable to
intravenous administration, but with greater ease, patient comfort and
convenience.
Alexza has five product candidates in clinical development. Alexza's lead
program, AZ-004 (Staccato loxapine) for the treatment of acute agitation in
schizophrenic or bipolar disorder patients, has completed one Phase 3 clinical
trial and the second Phase 3 clinical trial ongoing. For the acute treatment
of migraine headaches, AZ-001 (Staccato prochlorperazine) has completed Phase
2 testing and AZ-104 (Staccato loxapine) is in Phase 2 testing. Product
candidates in Phase 1 testing are AZ-003 (Staccato fentanyl) for the treatment
of breakthrough pain, which is partnered with Endo Pharmaceuticals in North
America, and AZ-007 (Staccato zaleplon) for the treatment of insomnia. More
information, including this and past press releases from Alexza, is available
online at http://www.alexza.com.
Safe Harbor Statement
This press release includes forward-looking statements regarding the
development, therapeutic potential, efficacy and safety of AZ-004. Any
statement describing a product candidate or Alexza's goals, expectations or
beliefs is a forward-looking statement, as defined in the Private Securities
Litigation Reform Act of 1995, and should be considered an at-risk statement.
Such statements are subject to certain risks and uncertainties, particularly
those inherent in the process of developing and commercializing drugs. The
Company's forward-looking statements also involve assumptions that, if they
prove incorrect, would cause its results to differ materially from those
expressed or implied by such forward-looking statements. These and other
risks concerning Alexza's business are described in additional detail in the
Company's Annual Report on Form 10-K for the year ended December 31, 2007, and
the Company's other Periodic and Current Reports filed with the Securities and
Exchange Commission including the risks under the headings: "Failure or delay
in commencing or completing clinical trials for our product candidates could
harm our business" and "If our product candidates do not meet safety and
efficacy endpoints in clinical trials, they will not receive regulatory
approval, and we will be unable to market them". Forward-looking statements
contained in this announcement are made as of this date, and the Company
undertakes no obligation to publicly update any forward-looking statement,
whether as a result of new information, future events or otherwise.
SOURCE Alexza Pharmaceuticals, Inc.

Thomas B. King, President & CEO of Alexza Pharmaceuticals, Inc.,
+1-650-944-7634, tking@alexza.com