VR-1 based drugs may offer utility in several inflammatory states.

Neurogen researchers believe that a drug that blocks the vanilloid receptor-1 (VR1), located on noiciceptive (peripheral) primary sensory neurons that transmit pain signals to the central nervous system for the perception of pain, could benefit patients suffering from various types of inflammatory and other pain states. Studies which model inflammatory pain in genetically altered mice lacking the VR1 receptor indicate a role of VR1 in the sensation of noxious heat as well as thermal hyperalgesia (heightened sensitivity to heat-induced pain). VR1 receptors are also found in the bladder and lungs, such that VR1 antagonists may have utility in cough and urinary incontinence.

Development Status

On November 8, 2007, Neurogen indicated that our partner for VR-1 based drugs, Merck, is planning to take the proof-of-concept compound MK 2295 (NGD 8243) forward in exploratory studies for the treatment of cough associated with upper airway disease and is focusing on a back-up compound, currently in preclinical development, for pain.

On June 5, 2007, Neurogen announced that development activities for NGD-8243 (MK-2295) would continue, based on promising preliminary results from proof-of-concept studies in its collaboration with Merck & Co, Inc. to research, develop, and commercialize small molecule medicines which work by targeting the vanilloid receptor (VR-1). Neurogen also announced that the research portion of the collaboration would conclude on August 28, 2007. Merck will continue development of NGD-8243 (MK-2295) and will owe milestone payments and royalties to Neurogen upon the commercialization of any VR-1 compounds from the research program.

Through the alliance, Neurogen and Merck have generated a broad spectrum of chemical intellectual property and several leading drug candidates, including NGD-8243, which is one of several drug candidates Merck is evaluating as a result of its exclusive worldwide alliance with Neurogen.

Neurogen and Merck entered into the collaboration in December 2003. As described in Neurogen SEC filings, the initial term of the research component of the collaboration was scheduled to expire in December 2006. In September 2006, the companies agreed to extend the research program on a rolling 90-day basis at Merck’s option. The companies will now conclude the research program in August 2007.