Myriad Genetics, Inc released new data on MPC-4505, its Neurokinin-1 (NK1) receptor antagonist, a drug candidate for chemotherapy-induced nausea and vomiting (emesis). MPC-4505 is a potent, orally bioavailable, CNS-penetrating, highly selective NK1 antagonist.

In an update of another important CNS drug development program at Myriad, the Company also announced that its Alzheimer's disease drug candidate, Flurizan, is progressing well. Patients have now been on drug for over five months and an independent Data Safety Monitoring Committee overseeing the trial has reported no serious safety concerns and recommends that the trial proceed. Myriad believes that the Phase II study in more than 200 patients with mild to moderate Alzheimer's disease will be completed in the clinic on schedule during the first calendar quarter of 2005.

MPC-4505 was selected from among a number of candidate compounds based on its potency and selectivity for NK1 receptors. Preclinical testing with the compound has demonstrated desirable pharmacokinetic characteristics. MPC-4505 achieved significant blood levels of drug after oral administration with a reasonable half-life. Concentrations of compound in the blood peaked about 4 hours after a single oral dose and remained at elevated levels for another 6 hours, in the Cynomolgus monkey.

Chemotherapy-induced nausea and vomiting is mediated via centrally-acting NK1 receptors and, therefore, any drug for this indication must have good penetration of the CNS. MPC-4505 achieves good penetration of the central nervous system, with a sustained brain concentration of compound over an extended period, as tested in the rat. MPC-4505 is also highly selective; it has an affinity for the NK-1 receptor subtype in the <1 nanomolar range.

"We are excited about the potential for this compound to treat both acute and delayed emesis in patients receiving highly emetogenic chemotherapies such as cisplatin," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "Improving tolerance to chemotherapy greatly enhances patient acceptance of cancer chemotherapy and may increase their compliance with the full prescribed course of chemotherapy. This compound adds to Myriad's portfolio of drugs for the treatment of cancer, which includes late stage preclinical drug candidates MPC-176716 for ovarian cancer and MPC-6827 for pancreatic and other cancers."

The NK1 receptor has been cloned and is a member of the G-protein coupled receptor family. The receptors are found on many cell types including central and peripheral neurons, smooth muscle cells, endothelial cells, fibroblasts, and immune cells. NK1 belongs to the neurokinin (NK) family of neuropeptides and exerts its biological effects via interaction with the NK1 receptor. The NK1-NK1 receptor system is one of the best-characterized neurotransmitter pathways in the central nervous system. NK1 receptor pathways have been implicated in the pathophysiology of emesis, anxiety and depression. Autoradiographic studies in monkey and human brains have shown a high expression of NK1 receptors in regions important for the regulation of affective behaviors and the neurochemical response to stress.