The overall scope of our Phase Two SBIR project has been to design, synthesize, and develop novel and patentable 5-HT2C-selective indole derivatives leading to the development of a clinical candidate to treat obesity, and ultimately to the approval of this candidate by the FDA. As a part of the proposed work in the parent grant, we had planned to resynthesize potent and selective compounds for further pharmacological evaluation if sufficient time was available. In October, 2008, Galenea Corporation and Organix signed an agreement to further the development of the lead compounds discovered on our SBIR grant. Galenea is a leading early stage pharmaceutical company based in Cambridge, MA. Together with Galenea, we have identified thirteen potent and selective 5-HT2C agonists for further development. In order to accelerate progress toward a clinical candidate, these compounds should be retested to confirm their selective 5-HT2C binding and functional activity against other 5-HT receptors, as well as in a broad panel of receptors and transporters. In vitro ADME (P450, pgp efflux, intrinsic clearance and human plasma protein binding) will need to be evaluated as well as in vivo pharmacokinetics and safety/toxicity (hERG, Ames, clastogenicity) for the most promising compounds. To carry out the proposed studies, it will be necessary to obtain 2-5 gram quantities of each of these compounds. Organix has designed and executed the small-scale synthesis of these compounds in the SBIR program, and also has considerable experience in synthesizing close analogs on the larger scale required here. Therefore, no difficulties are anticipated. As part of our collaboration, Galenea will support all of the pharmacological studies described above at no charge to the grant (see attached letter). Therefore we expect that approval of this grant supplement will greatly speed the development of a new and improved pharmaceutical agent as a treatment for obesity.