Chelsea’s unique portfolio of novel antifolate compounds was
originally developed by Dr. Gopal Nair and licensed by the company
in 2004. A library of orally available and metabolically inert
antifolate compounds with potent anti-inflammatory and anti-tumor properties,
these compounds are engineered to treat a broad range of immunological
disorders with fewer harmful and unpleasant side effects typically
associated with classical antifolates. Diseases that may potentially
be treated with metabolically inert antifolates include RA, psoriasis, inflammatory
bowel disease, cancer and other immunological disorders.
CH-1504, the lead product candidate in this portfolio, potently inhibits
several key enzymes that are required for cell proliferation including
dihydrofolate reductase (DHFR). Preclinical and clinical data to date
support CH-1504’s superior safety and tolerability, as well as
increased potency versus MTX, currently the leading antifolate treatment
and standard of care for a broad range of abnormal cell proliferation
diseases.
Chelsea reported positive preliminary results from its U.K. Phase
I trials for all oral indications of CH-1504 in December 2005 and anticipates
the initiation of Phase II trials for RA in 2007. Additionally,
an independent six-month pilot clinical study compared CH-1504 to MTX
in 20 RA patients in Peru. Although this pilot study will not be used
as a part of the regulatory approval process, the results of this study
suggest that CH-1504 has lower toxicity and improved tolerability,
as well as potentially increased efficacy versus MTX. Preclinical animal
models have also indicated that CH-1504 may have superior efficacy
and a greater therapeutics window than MTX.
