Concert Pharmaceuticals and Fast Forward established a collaboration to fund preclinical development of Concert’s deuterium-modified subtype–selective GAGAA modulator, C-21191, for the potential treatment of spasticity and pain in multiple sclerosis (MS). Fast Forward was established by the National Multiple Sclerosis Society (NMSS) for promoting translational research, encouraging academic-industrial collaborations, and funding the development of new MS therapies. As part of the agreement with Concert, Fast Forward will commit funding to support progression of the C-21191 program toward clinical development.
C-21191 is a nonsedating euterium-modified analog of L-838417, which was originally discovered by Merck and Co. Although preclinical testing by Merck indicated the compound had a promising pharmacological profile, it demonstrated a poor pharmacokinetic profile, and wasn’t progressed to the clinic. In contrast, Concert claims, preclinical studies indicate that C-21191 has much improved pharmacokinetic characteristics, without any loss of biochemical profile.
Concert is focused on exploiting its DCE Platform™ (deuterated chemical entity) platform for the development of drugs against a range of tumor types. The firm is primarily focused on the modification of previously characterized compounds, that have promising pharmacological properties but otherwise unacceptable ADME profiles. It claims selective deuterium modification has the potential, in certain cases, to improve ADME without altering desirable pharmacological properties.
Lead Phase II-stage candidate, CTP-499, is a deuterium-stabilized analog of HDX—an active metabolite of pentoxyfilline—and is in development as an adjunct to the treatment of diabetic nephropathy using ACE inhibitors or ARBs. Pentoxifylline itself has been approved for the treatment of intermittent claudication, but not kidney disease. Concert separately today announced the start of a Phase II study evaluating CTP-499 in about 170 patients with type 2 diabetes and mild-to-moderate (stage 2/3) chronic kidney disease.
Additional clinical and development-stage candidates are CTP-298, a protease inhibitor in Phase I development for the treatment of HIV, in partnership with GlaxoSmithKline. A deuterium-modified dextromethorphan candidate CTP-786 is progressing toward Phase I development as a treatment for neurological and psychiatric disorders, through a collaboration with Avanir Pharmaceuticals signed just last week. The agreement with Avanir gives the latter rights to multiple deuterium-modified dextromethorphan compounds.
Concert’s research programs include either in-house or partnered candidates for the treatment of hematologic cancers, epilepsy and depression, narcolepsy and fibromyalgia.