Alexza Initiates Second Phase 3 Clinical Trial For AZ-004 (Staccato(R) Loxapine)

Alexza
Pharmaceuticals, Inc. (Nasdaq: ALXA) announced that it has initiated
its second Phase 3 clinical trial with AZ-004 (Staccato(R) loxapine).
AZ-004 is an inhalation product candidate being developed for the treatment
of acute agitation in patients with schizophrenia or bipolar disorder.
Alexza believes the novel, non-invasive nature and rapid pharmacokinetic
(PK) properties resulting from inhaled loxapine administration via the
Staccato system have the potential to make AZ-004 a viable product to treat
acute agitation. AZ-004 is being developed through Symphony Allegro, a
product development partnership formed between Alexza and Symphony Capital,
LLC.


"We are excited to be advancing our AZ-004 NDA plan with the start of
the second Phase 3 clinical trial this year. We look forward to enrolling
this Phase 3 clinical trial as quickly as possible, and also releasing the
initial results from our first Phase 3 study before the end of September,"
said Thomas B. King, Alexza President and CEO. "This year is a transitional
year in our history, as we move into the commercial planning for the
manufacturing, quality systems, regulatory submissions, and potential sales
and marketing of AZ-004."



AZ-004 Second Phase 3 Clinical Trial Design



The second AZ-004 Phase 3 clinical trial is designed to enroll
approximately 300 patients diagnosed with bipolar I disorder and acute
agitation at 18 U.S. clinical centers. The trial is an in-clinic,
multi-center, randomized, double-blind, placebo-controlled study and will
test AZ-004 at two dose levels, 5 and 10 mg. Patients may receive up to 3
doses of study drug in a 24-hour period, depending on their clinical
status. Patients eligible for the study include those who are admitted
through an emergency department and those who are already in-patients in a
hospital setting, as long as they have acute agitation at the time of
patient randomization. This study is the first AZ-004 study enrolling
bipolar disorder patients. Alexza projects that this second Phase 3
clinical trial will take approximately 12 months to complete patient
enrollment.



The primary endpoint for the study is the change from baseline in the
PANSS (Positive and Negative Symptom Scale) Excited Component (also known
as PEC) score, measured at 2 hours after the first dose. Various
assessments of a patient's agitation state will be conducted at serial time
points using standard agitation scales over the first 4-hour post-dose time
period, with follow-up assessments at the end of the 24-hour study period.
Side effects will be recorded throughout the 24-hour period.



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 agitative state and would prefer a
rapid-acting, noninvasive treatment.



In summary, Alexza believes there is a significant unmet medical need
for an acute agitation treatment option that will provide a fast onset of
effect, that is noninvasive and safer to administer, and that allows
patients to be active participants in choosing acceptable treatment
options.



About AZ-004



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, 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. Alexza projects that the
initial results from the first Phase 3 study will be reported before the
end of September 2008.



The Company believes that the unique delivery of loxapine via the
Staccato system will provide rapid onset of drug effect, as measured by a
reduction in the signs and symptoms of acute agitation. In March 2007,
Alexza announced positive initial results from a multi-center, randomized,
double-blind, placebo-controlled Phase 2 clinical trial in 129 patients in
an in-patient clinical setting. The 10 mg dose of AZ-004 met the primary
endpoint of the clinical trial, which was a statistically significant
reduction in the measure of agitation from baseline to the 2-hour post-dose
time point, as compared to placebo. The 10 mg dose of AZ-004 also exhibited
a rapid onset of effect, with a statistically significant improvement in
the PEC scores at 20 minutes post-dose, as compared to placebo. The
effectiveness of the AZ-004 10 mg dose was sustained throughout the 24-hour
study period, as compared to placebo.



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 six 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, is in Phase 3
testing and completed the enrollment of its first Phase 3 clinical trial in
June 2008. AZ-001 (Staccato prochlorperazine) for the acute treatment of
migraine headaches has completed Phase 2 testing. AZ-104 (Staccato
loxapine) for the acute treatment of migraine headaches and AZ-002
(Staccato alprazolam) for the acute treatment of panic attacks associated
with panic disorder are 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
alexza.



Safe Harbor Statement



This press release includes forward-looking statements regarding the
development, therapeutic potential and safety of AZ-004, the development of
the Company's product candidates, projected clinical trial enrollment and
data reporting timelines, and safety of the Company's products and
technologies. Any statement describing the Company's 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 we undertake
no obligation to publicly update any forward-looking statement, whether as
a result of new information, future events or otherwise.


Alexza Pharmaceuticals, Inc.

alexza



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