Lexicon Genetics has revealed details of the preclinical development of a novel, orally available small molecule compound with potential application in the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
"LX2931 represents a potential new mechanism for the treatment of immune system disorders characterised by inappropriate lymphocyte activation," said Arthur Sands, Lexicon's president and chief executive officer.
According to a study that appeared in the Lancet Neurology, in northern Europe, continental North America, and Australasia, approximately one in every 1000 citizens suffers from multiple sclerosis, whereas in the Arabian peninsula, Asia, and continental South America, the frequency is much lower. In sub-Saharan Africa, MS is extremely rare.
However, The incidence of rheumatoid arthritis (RA) is 30 cases per 10,000 population. The peak incidence is between the ages of 40 and 60. The prevalence rate is 1 per cent, with women affected three to five times as often as men.
LX2931 is the third internal Lexicon drug discovery program to enter preclinical development in preparation for an Investigational New Drug (IND) application.
In preclinical models, LX2931 inhibits the in vivo activity of an enzyme that is associated with immune response and lymphocyte migration.
Lexicon discovered that mice lacking this enzyme displayed a dramatic reduction in T cells and B cells in the peripheral blood. In preclinical research, LX2931 reduced inflammatory response in mice and decreased lymphocyte counts in multiple species.
Lexicon is conducting preclinical research with lead small molecule compounds that inhibit LG267, a kinase that regulates immune cell activation and affects lymphocyte proliferation.
Lexicon discovered that mice lacking this kinase exhibit a reduced number of white blood cells.
Lexicon's lead compound in its LG267 drug discovery program blocks the in vivo activity of this kinase in preclinical models.
When dosed in mice in combination with chemotherapeutic agents, Lexicon's compound also increases neutrophil counts, and may protect against neutropenia caused by chemotherapy, potentially enhancing recovery from chemotherapy in cancer patients.
"We expect additional programs within our pipeline, such as LG267, to reach this milestone within the next few months. We continue to anticipate that we will file an IND for LX1031 for irritable bowel syndrome later this year," said Sands.