Profile: Chelsea Therapeutics International, Ltd. (CHTP.O)

Chelsea Therapeutics International, Ltd., incorporated April 2002, is a development-stage pharmaceutical company that focuses on acquiring and developing products for the treatment of a variety of human diseases. As of December 31, 2008, the Company focused its drug development resources on two clinical-stage development projects: droxidopa for symptomatic neurogenic orthostatic hypotension and other indications and its portfolio of non-metabolized antifolate compounds for the treatment of rheumatoid arthritis. It is developing droxidopa, an orally active synthetic precursor of norepinephrine and its investigational product candidate, for the treatment of neurogenic orthostatic hypotension (NOH). In addition to droxidopa, the Company is developing a portfolio of molecules for the treatment of various autoimmune/inflammatory diseases, including two clinical-stage product candidates: CH-1504 and CH-4051.

Droxidopa

The Company’s product candidates CH-1504 and CH-4051 are orally available molecules with anti-inflammatory, autoimmune and anti-tumor properties that inhibit several key enzymes that are required for cell proliferation. Droxidopa is approved and marketed by Dainippon Sumitomo Pharma Co., Ltd. (DSP) in Japan for the treatment of symptomatic orthostatic hypotension, freezing gait in Parkinson’s disease and hypotension associated with dialysis. CH-1504 is being investigated for the treatment of rheumatoid arthritis in a Phase II head-to-head clinical trial. CH-4051 is being investigated in a Phase I study.

In January 2007, the United States Food and Drug Administration (FDA) granted orphan drug status for droxidopa for the treatment of symptomatic NOH in patients with primary autonomic failure (Parkinson’s disease, multiple system atrophy (MSA), and pure autonomic failure (PAF)), dopamine-ß-hydroxylase deficiency, or nondiabetic autonomic neuropathy. In August 2007, the European Commission granted two orphan medicinal product designations for droxidopa for the treatment of orthostatic hypotension in patients with PAF and MSA. The Company initiated a Phase II trial of droxidopa, both alone and in combination with carbidopa for the treatment of Fibromyalgia in January 2009. The Phase II trial is a multi-centre, randomized, double-blind, placebo-controlled, dose response, factorial 12-arm parallel group study evaluating 120 patients equally randomized to receive droxidopa monotherapy, carbidopa monotherapy, droxidopa/carbidopa combination therapy or placebo.

Metabolically Inert Antifolates

Drug candidates from this portfolio, including both clinical candidates CH-1504 and CH-4051, inhibit dihydrofolate reductase, an enzyme required for cell proliferation. Its portfolio of metabolically inert antifolates consists of two clinical stage drug candidates and additional preclinical candidates. CH-1504, the Company’s clinical-stage antifolate compounds, is being developed for a lead indication in rheumatoid arthritis. CH-4051, the second clinical stage compound in this portfolio is being developed in rheumatoid arthritis. In November 2008, the Company commenced a Phase I trial of CH-4051 in healthy male volunteers. The randomized, double-blind placebo controlled study was designed to evaluate the safety, tolerability and pharmacokinetics of ascending doses of CH-4051.

I-3D Portfolio

I-3D portfolio is a group of orally active compounds that inhibit the enzyme dihydroorotate dehydrogenase (DHODH) for the treatment of autoimmune diseases and transplant rejection. At the time of the agreement, Active Biotech had already isolated more than 15 compounds and conducted preclinical modeling resulting in the identification of two potential lead compounds.

The Company competes with Abbott Laboratories, Amgen, Sanofi-Aventis, Barr Laboratories, Boehringer Ingelheim Pharma, Hoffmann-La Roche, Johnson & Johnson, Bristol-Myers Squibb, Mylan Laboratories, Shire, Mylan Pharmaceuticals, Eon Labs, Impax Laboratories, King Pharmaceuticals, Pfizer, Rigel and Celltech.