Rejuvenon's RC-1291 Ghrelin Mimetic Receives Fast Track Designation from FDA for Cancer Anorexia/Cachexia.

BRIDGEWATER, N.J. -- Rejuvenon Corporation, a privately held pharmaceutical company developing therapeutics for cancer and metabolic disorders, has received US Food and Drug Administration (FDA) "fast track" designation for its investigational compound, RC-1291, a small-molecule ghrelin mimetic, for the treatment of cachexia (loss of body weight) and anorexia (loss of appetite) in cancer patients. The anorexia/cachexia syndrome is a common, life-threatening complication of underlying malignancies.

"There is a significant unmet need for a pharmaceutical treatment in cancer cachexia," said Gary C. Cupit, PharmD, president and chief executive officer of Rejuvenon. "Unexpected weight loss is an all-too-common and devastating consequence of cancer. Currently, effective treatments are lacking and the patient population in need of an effective treatment is substantial. Clinicians and patients are seeking a product that offers the potential we see in Rejuvenon's lead candidate, RC-1291."

The fast-track programs of the FDA are designed to facilitate the development and expedite the review of new drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. In its letter to Rejuvenon, the FDA stated that based on preclinical and early clinical data, RC-1291 shows potential as a treatment for cancer anorexia/cachexia. This syndrome frequently accompanies malignant disease states and often results in the death of the patient. In these patients, weight loss is an independent risk factor for poor survival, and cachectic patients also suffer increased complications from surgery, radiotherapy, and chemotherapy. To date, there are no effective treatments approved for this indication.

"Preclinical and clinical data have demonstrated the potent appetite-stimulating effects of RC-1291," said William J. Polvino, MD, Rejuvenon's senior vice president of development. "In addition, RC-1291 has potential anabolic attributes that we expect to reduce or eliminate the ongoing loss of body weight and/or muscle mass. No other agent provides the dual actions of potent appetite stimulation and anabolic activity. Consequently RC-1291 represents an important therapeutic prospect in the treatment of cancer anorexia/cachexia. We expect intervention with RC-1291 to improve appetite and food intake and attenuate or reverse ongoing weight loss. Additional benefits may include improvements in quality of life and functional performance."

About Ghrelin and RC-1291

The recent discovery of ghrelin-mediated effects on appetite opens a new avenue for pharmaceutical treatment. Ghrelin is a small endogenous protein that acts on the Growth Hormone Secretagogue Receptor (GHSR), a G-Protein Coupled Receptor recognized as a key control point in the growth hormone signaling pathway. The GHSR is a target for treatment of several metabolic disorders including those related to maintenance of ideal body weight and composition. Agonists for this receptor have been identified as drug candidates for treatment of wasting and body fat redistribution syndromes associated with a range of diseases, such as cancer and AIDS. However, potential clinical use of ghrelin itself for wasting disorders is limited, because it must be administered by injection.

RC-1291 is a synthetic, small-molecule ghrelin mimetic that binds to, and stimulates, the GHSR. Unlike ghrelin, RC-1291 can be delivered by mouth. This highly potent, orally available compound is intended to be administered as a convenient once-daily treatment for patients with cancer anorexia/cachexia. The compound has been studied in a series of seven completed or ongoing clinical studies in human volunteers, including a double-blind placebo-controlled study in which, compared to placebo, RC-1291 significantly increased appetite and spontaneous food intake. Under the FDA fast-track designation, Rejuvenon plans to conduct Phase II trials later this year.

In addition to the known stimulation of appetite and food intake via central orexigenic pathways, additional mechanisms of action of RC-1291 may be relevant in treating cancer anorexia/cachexia. Loss of appetite and body weight associated with cancer is somewhat driven by circulating inflammatory cytokines such as TNF-alpha (originally named "cachectin") and IL-6. Recent studies have shown that activation of the ghrelin receptor may play a direct role in reducing the production and circulating levels of inflammatory cytokines such as TNF-alpha. Ghrelin and RC-1291 are both highly potent agonists at the same receptor, thus experimental data generated with ghrelin help to validate use of RC-1291 in cancer anorexia/cachexia.

Dr. Cupit added, "Our lead program is a superb example of the dynamic synergy of Rejuvenon's big pharma/biotech partnering strategy. We are delighted that the development team has reached this milestone so rapidly from a preclinical candidate into Phase II. We are equally pleased with the consensus between Rejuvenon and the FDA in recognizing cancer anorexia/cachexia as an important unmet medical need. Our efforts are now focused on speeding the development of RC-1291 by generating the data needed to bring the product to market. Believing that this represents the first of many potential opportunities, we will continue to leverage the skills of our expanding development team through additional product acquisitions."

About Rejuvenon

Rejuvenon, founded in 2000 by Dr. Roy G. Smith of the Baylor College of Medicine, is a private pharmaceutical development company whose strategy is to in-license and develop promising drug candidates that are ready for preclinical or clinical testing. The company is developing small molecule drugs to treat metabolic and oncologic diseases for which existing therapies are limited or marginally effective. Rejuvenon's first portfolio of drug candidates were in-licensed as preclinical compounds from Novo Nordisk in May 2001. RC-1291 is the furthest advanced of this series of orally-deliverable compounds for treatment of cancer-related weight loss. The company is moving several additional molecules through preclinical development. As development proceeds on these compounds, Rejuvenon is actively seeking other preclinical in-licensing candidates to fill the development pipeline.