Neurolixis

Neurolixis is a biopharmaceutical company focused on novel drugs for the treatment of human central nervous system diseases.

Neurolixis

Industry	Biopharmaceuticals
Founded	2011
Headquarters	United States
Key people	Mark A. Varney, Adrian Newman-Tancredi

Neurolixis Inc. was founded in 2011 by Mark A. Varney, PhD, and Adrian Newman-Tancredi, PhD, DSc. (Chief Executive Officer [1]). The company's therapeutic focus is on CNS disorders including Parkinson's disease, neurological orphan disorders, depression and cognitive deficits.[2] The company has offices in USA and in France.[3]

In September 2013, Neurolixis in-licensed two clinical-phase drugs from Pierre Fabre Laboratories, a French pharmaceutical company. The drugs (befiradol and F-15599) are targeted to the treatment of dyskinesia in Parkinson's disease and to breathing deficits in Rett syndrome, respectively.[4] In addition, Neurolixis is developing its own novel chemical entities (NCEs).

Neurolixis has been awarded a series of research grants by the Michael J. Fox Foundation and by Parkinson's UK. Neurolixis undertook research examining the effects of novel, highly selective and efficacious serotonergic drugs targeting 5-HT1A receptors in brain regions relevant to therapeutic properties in Parkinson's disease.[5] The Michael J. Fox Foundation subsequently announced that it was supporting proof-of-principle studies on befiradol (also known as NLX-112) in models of Parkinson's disease[6] and showcased Neurolixis in its Partnering Program.[7] In January 2018, the British charity Parkinson's UK announced that it had awarded Neurolixis a grant to advance development of befiradol up to clinical phase in Parkinson's disease patients.[8] In March 2019, Neurolixis announced that the US Food and Drug Administration (FDA) gave a positive response to Neurolixis' Investigational New Drug (IND) application for befiradol to be tested in a Phase 2 clinical study in Parkinson's disease patients with troublesome Levodopa-induced dyskinesia.[9] Studies published in 2020 using non-human primate models of Parkinson's disease, (MPTP-treated marmosets and MPTP-treated macaques), found that befiradol potently reduced Levodopa-induced dyskinesia at oral doses as low as 0.1 to 0.4 mg/kg.[10][11]

On 22 November 2020, The Sunday Times reported that the two charities, Parkinson's UK and Michael J. Fox Foundation, were jointly investing $2 million to support a clinical trial on befiradol in Parkinson's disease patients with troublesome Levodopa-induced dyskinesia, a potentially "life changing" drug.[12] On 23 November 2020, Parkinson's UK and Michael J. Fox Foundation, confirmed their funding in an official announcement.[13]

F-15599 (also known as NLX-101) was awarded Orphan Drug Status by the United States Food and Drug Administration (FDA) in October 2013[14] and Orphan Medicinal Product designation by the European Medicines Agency in March 2014.[15] In collaboration with researchers at the University of Bristol, Neurolixis has been awarded a grant by the International Rett Syndrome Foundation to study F-15599 in animal models of Rett syndrome.[16] In June 2015, Neurolixis was awarded a grant by the Rett Syndrome Research Trust to advance F-15599 to clinical development.[17] Subsequent studies on F-15599 investigated its functional selectivity (also referred to as 'biased agonism') at cortical serotonin 5-HT1A receptors using brain imaging techniques in rat: functional magnetic resonance imaging[18] and positron emission tomography.[19] The functional selectivity of F-15599 was considered to underlie its rapid-acting antidepressant-like activity in the 'chronic mild stress' (CMS) model of depression. F-15599 reversed CMS-induced anhedonia (measured as a deficit in sucrose solution consumption) after a single day of treatment.[20]

In addition to developing befiradol and F-15599, Neurolixis is also developing its own novel chemical entities (NCEs) in collaboration with a team at Jagiellonian University in Krakow, Poland. Scientists from Neurolixis and Jagiellonian University filed a patent application on the NCEs in 2016,[21] and it issued in the USA under patent number US10562853B2.[22] The NCEs are selective serotonin 5-HT1A receptor agonists that show functional selectivity for either extracellular signal-regulated kinases activation[23] or for beta arrestin activation.[24] It has been suggested that such compounds may have utility for treatment of distinct CNS disorders.[25]