Manhattan Pharmaceuticals, Inc. (AMEX: MHA)
www.manhattanpharma.com
--Orally administered Oleoyl-estrone (OE) for treatment for obesity is a synthetic form of a hormone produced naturally in the body. Oleoyl-estrone's mechanism of action is to suppress appetite by communicating the body's level of fat tissue to the brain. Early clinical results of weight loss demonstrated by Manhattan Pharma's OE are promising and suggest OE may also hold the potential for durability in weight loss after dosing stops. The company plans to initiate a Phase IIa trial in the first half 2006.

Nastech Pharmaceutical Co. (Nasdaq: NSTK)
www.nastech.com
--Intranasal PYY 3-36 for obesity treatment is a synthetic form of Peptide YY, a naturally occurring human hormone produced after each meal by specialized endocrine cells in the gut; the amount of PYY secreted is in proportion to the calorie content of the meal. Early research has demonstrated the role of PYY in regulating appetite control by sending the brain a signal to stop eating. Nastech's product has completed several Phase I clinical trials, and the company plans to conduct additional dose-optimization studies before commencing Phase II trials.

Arena Pharmaceuticals (Nasdaq: ARNA)
www.arenapharm.com
--Orally administered APD356 for treating obesity enhances a brain receptor that regulates satiety and hunger. APD356 is a novel and selective 5-HT2C receptor agonist for obesity that appears to stimulate the 5-HT2C serotonin receptor more selectively than does fenfluramine and dexfenfluramine (also known as fen-phen). Because of this selectivity, Arena believes APD356 is unlikely to cause the cardiovascular side effects associated with those compounds. Arena's product is currently in Phase IIb trials, and the company expects to begin Phase III clinical development in the second half of 2006.

Emisphere Technologies (Nasdaq: EMIS)
www.emisphere.com
--Orally administered PYY3-36 is an oral version of Peptide YY (PYY), the hormone that is secreted post-prandially (after a meal) by the endocrine cells of the distal gastrointestinal tract in proportion to the caloric content of a meal. There is published clinical evidence that elevated PYY levels contribute to weight loss and decreased food intake. In addition, studies have shown that blood levels of PYY are drastically elevated in individuals who have undergone gastric bypass surgery, an effective treatment for morbid obesity. An oral form of PYY would be patient friendly and ensure compliance to the dosing regimen.

Cytos Biotechnology AG - Swiss company (SWX: CYTN)
www.cytos.com
--CYT009-GhrQb Vaccine for treating obesity is an injectable form of naturally occurring ghrelin, an amino acid hormone that has been identified as a regulator of appetite. Ghrelin is produced in the stomach and travels via the bloodstream to the brain where it exerts its activity. Vaccination with the drug is anticipated to induce antibodies that bind circulating ghrelin and thereby inhibit its entry into the brain. Preventing ghrelin from accessing the brain via vaccination could be an effective means to reduce its appetite-stimulating effect. Cytos' product is currently in a combined Phase I/IIa study, with early results expected in the second half of 2006.

Metabolic Pharmaceuticals Ltd.- Australian company (ASX: MBP)
www.metabolic.com.au
--Orally administered AOD9604 is a peptide variant of hGH 177-191, a fragment of human growth hormone that improves fat metabolism. Australian researchers have established there is a small region of the growth hormone molecule (less than one tenth of its total size), denoted hGH 177-191, that appears to be responsible for its specific effect on fat and also appears not to have any effect on growth or on insulin resistance. Early clinical studies confirmed that the drug elicits the expected fat metabolic response, by both oral and injected routes of administrations. There were also encouraging indications of weight loss measured one week after administration. The product is now in Phase IIb trials.

VIVUS, Inc. (Nasdaq: VVUS)
www.vivus.com

VIVUS's proprietary oral obesity therapeutic, QnexaT, incorporates the active ingredients from two previously approved weight loss products. In doing so, the compound addresses appetite and satiety, two main mechanisms that affect eating behavior. In a recent Phase II clinical trial conducted at Duke University, Qnexa demonstrated nearly double the weight loss in less than half the time as compared to the leading obesity drug in development. Clinical data also indicates that Qnexa may potentially offer a significantly improved side effect profile as compared to other therapeutic options. The Phase III program for Qnexa is scheduled for 2007 and will include two PK trials designed to optimize the drug formulation and evaluate pharmacokinetics as well as several 56-week trials to evaluate safety and efficacy.