Mithridion, Inc. a privately-owned clinical stage drug development company focusing on serious Central Nervous System (CNS) disorders, announces that the US Food and Drug Administration (FDA) has awarded orphan drug designation for MCD-386CR, its lead drug candidate, for the treatment of Progressive Supranuclear Palsy (PSP).

Orphan status entitles Mithridion to seven years of market exclusivity upon approval of MCD-386 for treating PSP, and to apply for grant funding to contribute to clinical trial costs, tax credits, and a waiver of certain FDA fees. Orphan status is intended to encourage the development of drugs for diseases affecting fewer than 200,000 persons in the USA.

PSP is a progressive brain disease in which neurons degenerate in regions of the brain vital for eye movements, balance, walking, speech, and cognition. Cognitive impairment typically involves slowed thinking, and difficulties with reasoning, planning, and shifting between tasks, caused by dysfunction of the brain's executive functions. This has been called “dysexecutive syndrome.”

“Orphan status will help us immeasurably to bring together the resources and support needed to evaluate MCD-386CR in this rare but important disease, and indeed in other devastating brain diseases for which there are no current therapies,” said Trevor M Twose, PhD, the company's chief executive. “Based on results in preclinical studies, we believe MCD-386CR potentially will help restore cognition, so vital to human functioning, and potentially could treat the underlying processes causing the degeneration of neurons in PSP.”

As a part of its recently-articulated strategy, Mithridion is actively exploring opportunities to develop its drug candidates in niche market opportunities in serious CNS or brain disorders, in addition to more common diseases, such as Alzheimer's disease and schizophrenia. Several promising disease targets in addition to PSP have been identified and are currently being evaluated. The company believes that it will be able to create additional high value and strong entry barriers through this strategy, which it intends to fund using a combination of equity capital and non-dilutive funding. Furthermore, the company believes that it can reduce clinical trial costs and improve its ability to demonstrate proof-of-efficacy for its candidate drugs by selecting for clinical trials neurological disorders, such as PSP, with more “pure play” pathogenesis or symptoms, and by using novel biomarkers and neuropsychological tests specific for particular domains of cognition, such as executive functions.

MCD-386 is a highly selective agonist (activator) for M1-type acetylcholine muscarinic receptors, effectively mimicking acetylcholine in a selective way to achieve desired therapeutic effects while minimizing side effects. Acetylcholine is a chemical 'neurotransmitter' vitally involved in maintaining brain health and in many brain functions such as memory, cognition, executive functions, and attention. MCD-386 was designed to stimulate these and other key brain functions that have been compromised by the deficit of acetylcholine that is a characteristic feature of PSP.

MCD-386 has completed phase I single- and multi-dose clinical trials in 55 healthy volunteers, including 29 subjects who received a controlled release tablet formulation. MCD-386CR has so far proven to be well-tolerated at the doses tested. Extensive pharmacokinetic information obtained during the trials demonstrated sustained release of drug substance from the formulation, and, together with other trial results, provides a strong foundation for further rational development of MCD-386.

The development of MCD-386 was supported in part by NIH SBIR grant AG20454 from the National Institute of Aging, and the NIH RAID Programme. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Aging, or the National Institutes of Health.