Targacept Starts Phase 2b Clinical Trial Of TC-5214 As Augmentation Treatment In Major Depressive Disorder

Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics™, today announced that it has initiated a Phase 2b clinical trial of TC-5214 as an augmentation therapy in subjects with Major Depressive Disorder (MDD). TC-5214 is a broad spectrum neuronal nicotinic receptor (NNR) antagonist and represents a promising new mechanism in development for the treatment of MDD.


"The millions of patients suffering from depression who do not respond well to the currently available first-line therapies need help," said Dr. Madhukar H. Trivedi, Professor and the Director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center at Dallas and one of the principal investigators in the National Institute of Mental Health's large-scale STAR*D study. "There is a great unmet medical need for effective second and third line treatments with novel mechanisms of action to augment existing therapies and improve clinical outcomes for these patients. I am very enthusiastic about the potential for NNR-targeted compounds and other novel mechanisms to serve this need."


The design of the Phase 2b trial of TC-5214 includes two phases. In the first phase, subjects diagnosed with MDD will receive citalopram hydrobromide, a selective serotonin reuptake inhibitor (SSRI), for eight weeks to determine the extent of therapeutic response. Subjects who have not responded well based on predefined criteria would be randomized into the double blind second phase of the trial and receive either TC-5214 or placebo, together with continued citalopram therapy, for an additional eight weeks. It is expected that approximately 560 subjects will participate in the first phase of the trial and approximately 220 subjects will be randomized into the second phase of the trial. The primary endpoint of the trial is change from baseline during the second phase of the trial as measured by the Hamilton Depression Rating Scale. The trial will also collect information on a variety of secondary safety and efficacy measures. The trial is planned to be conducted at sites in the United States and India.


"The initiation of this Phase 2b clinical trial, just four months after TC-5214 initially entered the clinic, reflects not only our enthusiasm for its therapeutic promise but also our ability to execute against a very aggressive development plan," said J. Donald deBethizy, Ph.D., President and Chief Executive Officer of Targacept. "We believe that the favorable preclinical profile of TC-5214, combined with the positive results from our previous Phase 2 clinical trial of mecamylamine as an augmentation treatment for MDD, bode well for TC-5214's potential for clinical success."


About TC-5214


It is well known that depressive symptoms can result from an overstimulation of NNRs and other receptors in the brain that are activated by the neurotransmitter acetylcholine. Accordingly, compounds capable of inhibiting the activity of these overstimulated receptors, known as antagonists, may be expected to have antidepressant effects. In a prior Phase 2 clinical trial conducted by Targacept, subjects with MDD whose treatment with citalopram was augmented with mecamylamine hydrochloride showed greater improvement on symptoms of depression than subjects who received continued citalopram treatment and placebo.















TC-5214 is the S(+) enantiomer of mecamylamine hydrochloride. TC-5214 has exhibited an overall therapeutic profile superior to mecamylamine in preclinical models of depression and anxiety (Lippiello et al., accepted for publication in CNS Neuroscience & Therapeutics), a finding consistent with laboratory studies showing TC-5214 to more effectively inhibit the activity of the alpha4beta2 NNR.


About MDD


According to The National Institute of Mental Health, MDD is the leading cause of disability in the United States for people between the ages 15 and 44. The NIMH estimates that approximately 14.8 million American adults suffer from MDD.


The Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study undertaken by the National Institute of Mental Health between 2001 and 2006 showed the inadequacy of currently available therapies for MDD. In the first phase of the STAR*D study, approximately 2,800 persons with MDD were given citalopram for 12 to 14 weeks. Only about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. The second phase of the STAR*D study evaluated the effects of augmentation with a new medication or switching to a different treatment for participants who did not respond or only responded partially to citalopram. Approximately one in four of these participants reached remission. These findings have been cited as highlighting the need for more broadly effective antidepressant treatments (Rush, et al., NEJM Volume 354:1231-1242, March 23, 2006 Number 12).


About Targacept


Targacept is a clinical-stage biopharmaceutical company that discovers and develops NNR Therapeutics™, a new class of drugs for the treatment of central nervous system diseases and disorders. Targacept's product candidates selectively modulate neuronal nicotinic receptors that serve as key regulators of the nervous system to promote therapeutic effects and limit adverse side effects. Targacept has product candidates in development for Alzheimer's disease, cognitive dysfunction in schizophrenia, pain and depression, as well as multiple preclinical programs. Targacept also has a cognition-focused collaboration with AstraZeneca and a strategic alliance with GlaxoSmithKline. Targacept's news releases are available on its website at targacept.


Forward-Looking Statements

Statements in this press release that are not purely historical in nature, including, without limitation, statements regarding the progress, timing or scope of the research and development of TC-5214 or related regulatory filings or clinical trials, including the number of subjects to be included in the ongoing Phase 2b trial, the benefits that may be derived from TC-5214, our plans, expectations, future operations, financial position, revenues, costs or expenses, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those expressed or implied by forward-looking statements as a result of various important factors, including risks and uncertainties relating to: the results of clinical trials and non-clinical studies and assessments with respect to TC-5214, including whether the results of our completed Phase 2 clinical trial of racemic mecamylamine as an augmentation treatment for MDD and positive findings in preclinical studies of TC-5214 are predictive of the results of the ongoing Phase 2b clinical trial and any future clinical trials of TC-5214; the conduct of such trials, studies and assessments, including the performance of third parties that we engage to execute them and difficulties or delays in the completion of subject enrollment or data analysis; the timing and success of submission, acceptance and approval of regulatory filings with respect to TC-5214; our ability to obtain, maintain and enforce patent protection for TC-5214; and our ability to obtain substantial additional funding. These and other risks and uncertainties that may impact actual results are described in greater detail under the heading "Risk Factors" in our most recent Annual Report on Form 10-K and in other filings that we make with the Securities and Exchange Commission. As a result of the risks and uncertainties, the results or events indicated by the forward-looking statements may not occur. We caution you not to place undue reliance on any forward-looking statement. In addition, any forward-looking statements in this release represent our views only as of the date of this release and should not be relied upon as representing our views as of any subsequent date. We anticipate that subsequent events and developments may cause our views to change. Although we may elect to update these forward-looking statements publicly at some point in the future, we specifically disclaim any obligation to do so, except as required by applicable law.


Source

Alan Musso

Targacept, Inc., VP and CFO

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