OREXIGEN(TM) Therapeutics Initiates its Third Phase III Trial for Contrave(TM) to Treat Obesity.

SAN DIEGO -- Orexigen[TM] Therapeutics, Inc. (Nasdaq: OREX), a biopharmaceutical company focused on the treatment of central nervous system disorders including obesity, today announced the initiation of the third trial in its Phase III clinical trial program for its lead product candidate Contrave[TM] as a treatment for obesity. The program includes a set of four Phase III trials evaluating a variety of obesity-related outcome measures.

This clinical trial is a 58-week study designed to assess the safety, tolerability and efficacy of Contrave in healthy, nondiabetic, obese patients. The trial is designed to take place at approximately 40 centers nationwide and Orexigen plans to enroll approximately 1650 patients.

"Contrave is a unique approach to weight loss based on our understanding of how the human brain regulates both what and how much we eat," said Gary Tollefson, M.D., Ph.D., Orexigen President and CEO. "We believe Contrave activates a center in the brain resulting in a reduction in appetite and an increase in our expenditure of energy. Moreover, Contrave has been shown to mitigate the body's typical effort to offset early weight loss, sometimes referred to as the 'diet plateau.'" In addition, Dr. Tollefson indicated that the Company is further evaluating Contrave's effect on both metabolic and behavioral indicators associated with obesity.

With the initiation of this trial, patient recruitment is now underway for three Contrave Phase III trials. Please see www.clinicaltrials.gov for more information. Orexigen expects to begin a fourth Phase III trial for Contrave in the fourth quarter of 2007.

In April, Orexigen initiated enrollment in its first Phase III clinical trial, a 56-week study designed to evaluate Contrave's weight loss potential alone or when combined with intense diet, exercise and behavior modification. This trial is taking place at nine centers nationwide and plans to enroll approximately 800 patients.

In May, Orexigen initiated enrollment in its second Phase III clinical trial, a 56-week study designed to assess both the safety and efficacy of Contrave in obese subjects who also have been diagnosed with Type II diabetes. Recent studies have demonstrated that obesity is a leading risk factor for various metabolic disorders, such as diabetes, and this trial is designed to evaluate weight loss and factors related to glucose metabolism. The trial is taking place at approximately 40 centers nationwide and Orexigen plans to enroll approximately 525 patients.

Contrave is a proprietary fixed dose combination of bupropion SR (sustained release) and Orexigen's novel formulation of naltrexone SR in a single tri-layer tablet. Orexigen chose these two constituent drugs based on the results of its model used to screen potential drug combinations and Orexigen's understanding of circuitries in the brain that regulate appetite and energy balance. In a previous Phase IIb multi-center clinical trial, Contrave demonstrated statistically significant weight loss at 48-weeks compared to bupropion SR alone, naltrexone IR (immediate release) alone, and placebo.

About Orexigen Therapeutics

Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the development of pharmaceutical product candidates for the treatment of central nervous system disorders including obesity. Orexigen's lead combination product candidates targeted for obesity are Contrave[TM], which is in Phase III clinical trials, and Empatic[TM], which is in the later stages of Phase II development. Both product candidates are designed to take advantage of the Company's understanding of how the brain appears to regulate appetite and energy expenditure, as well as the mechanisms that come into play to limit weight loss over time. Each product candidate is designed to act on a specific group of neurons in the central nervous system with the goal of achieving appetite suppression and sustained weight loss. Further information about the Company can be found at http://www.Orexigen.com

Forward-Looking Statements

Orexigen cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward-looking statements. These statements are based on Orexigen's current beliefs and expectations. These forward-looking statements include statements regarding the enrollment of Phase III trials and the efficacy and safety of Contrave, and the potential to obtain regulatory approval for, and effectively treat obesity with, Contrave. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in Orexigen's business, including, without limitation: the progress and timing of Orexigen's clinical trials; the potential that earlier clinical trials may not be predictive of future results; the ability for Contrave to receive regulatory approval on a timely basis or at all; the potential for adverse safety findings relating to Contrave to delay or prevent regulatory approval or commercialization, or result in product liability claims; the potential that Orexigen's scientific theories relating to the effects that Contrave may have on metabolic and behavioral indicators associated with obesity; Orexigen and its licensors may not be able to obtain, maintain and successfully enforce adequate patent and other intellectual property protection of its product candidates; and other risks described in Orexigen's filings with the Securities and Exchange Commission (SEC), including those detailed under the heading "Risk Factors" in Orexigen's Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 filed with the SEC on August 10, 2007. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.