Neurolixis to Present Positive Proof-of-Concept Results on NLX-112 at World Parkinson’s Congress  (WPC).

NLX-112, a first-in-kind, highly selective, serotonin 5-HT1A receptor activator, recently underwent a successful Phase 2A clinical trial for treatment of levodopa-induced dyskinesia in Parkinson's disease. The detailed results from the trial, which met its primary and secondary endpoints, will be presented at the WPC in Barcelona as a poster on Wednesday July 5^th 2023 (poster board # LBP38.31) and in an oral presentation on Friday July 7^th 2023 (morning Hot Topics session). If you are attending this meeting, come and meet us!

See the full press release.

Neurolixis, Inc. today announced the positive results of its Phase 2A clinical trial with NLX-112 (befiradol), for treatment of levodopa-induced dyskinesias (LID) in Parkinson’s disease (PD).
NLX-112, a first-in-kind, highly selective serotonin 5-HT1A receptor activator, met the primary outcome of safety and tolerability and, in addition, showed statistically significant efficacy in reducing LID symptoms in Parkinson’s disease patients.

The study (ClinicalTrials.gov ID: NCT05148884) was a randomized, double-blind, placebo-controlled trial conducted at 5 centers in Sweden. 22 patients (15 on NLX-112, 7 on PBO) completed the 8-week treatment according to the protocol. Safety was good and did not differ between NLX-112 and placebo groups. Tolerability was favorable, there were no serious adverse events in the NLX-112 group. Beyond meeting the primary outcome of safety and tolerability, NLX-112 also achieved significant reductions in LID scores, whereas placebo group changes were not significant. Full analysis of efficacy measures is underway and will be disclosed in further announcements and at upcoming scientific conferences. 

"We are excited about the positive results of this proof-of-concept study," said Prof. Per Svenninsson, Principal Clinical Investigator at the Karolinska institute in Stockholm. "The findings indicate that NLX-112 can be safely administered to people with PD and alleviates their troublesome LID. If these findings are confirmed in larger clinical trials, NLX-112 could become a promising new treatment option for this indication."

The study was financially supported by grants from Parkinson's UK and The Michael J. Fox Foundation, the two largest foundations for research on Parkinson's disease  in the world.
Neurolixis plans to advance NLX-112 to a Phase 2B study to further evaluate the drug's efficacy and safety in a larger patient population.

Neurolixis, Inc. today announced the appointment of Dr. Christopher Jankosky, MD, MPH, as its Chief Medical Officer. 
"We are thrilled to have Dr. Jankosky join our team as Chief Medical Officer," said Adrian Newman-Tancredi, PhD, DSc, CEO of Neurolixis. "His deep understanding of the medical needs in the neurology area and of the drug development process will be invaluable as we continue to advance our pipeline and bring new therapies to patients."
Dr. Jankosky has spent over 20 years in senior medical and healthcare roles. As Chief Medical Officer, Dr. Jankosky will be responsible for leading the company's clinical development strategies, overseeing the design and conduct of clinical trials, and ensuring that Neurolixis remains at the forefront of innovation in the industry. He had previously been a member of the Neurolixis Scientific Advisory Board since 2021.
"I am honored to join Neurolixis and be part of such a talented and dedicated team," said Dr. Jankosky. "I am passionate about finding solutions to unmet medical needs and excited to contribute to Neurolixis' mission of improving the lives of patients through cutting-edge treatments."

New data from researchers at the University of California at Riverside show that the novel chemical entity, NLX-101, potently reverses sensory overload in a transgenic mouse model of Fragile X syndrome.  The study, published in the peer-reviewed journal  Neuroscience, examined the effects of NLX-101 on audiogenic seizures (i.e., seizures that are triggered by a loud noise) in mice that lack expression of Fragile X Messenger RibonucleoProtein (FMRP), thus mimicking human Fragile X syndrome. NLX-101, a selective 5-HT1A receptor biased agonist, potently and almost completely protected the mice from seizures, an effect that was maintained upon repeated treatment and reversed by co-administration of selective 5-HT1A receptor antagonists. 

The results, generated in collaboration with Drs. Khaleel Razak and  Xin Tao,  suggest that NLX-101 can attenuate the damaging sensory hypersensitivity seen in Fragile X syndrome patients. Fragile X syndrome, for which there are no approved treatments, is characterized by social impairment and communication difficulties, and is the most common Autism Spectrum Disorder, affecting approximately 50 000 patients in the US and a similar number in Europe. NLX-101 has previously shown robust activity in rodent models of cognition, mood deficits and Rett syndrome, and has begun Phase 1 human study . 

Adrian Newman-Tancredi, CEO of Neurolixis, commented: “Autism Spectrum Disorders, such as Fragile X syndrome, cumulatively affect an estimated 1 in 100 children, causing a substantial suffering as well as a medical and social burden. The present data support further development of NLX-101 for treatment of Fragile X syndrome and related clinical indications." 

Acute and Repeated Administration of NLX-101, a Selective Serotonin-1A Receptor Biased Agonist, Reduces Audiogenic Seizures in Developing Fmr1 Knockout Mice.
Tao X, Newman-Tancredi A, Varney MA, Razak KA.
Neuroscience. 2022 Nov 21:S0306-4522(22)00570-X. doi: 10.1016/j.neuroscience.2022.11.014, PMID: 36410632

New data, just published in Behavioral Brain Research, shows robust activity of the Neurolixis drug development candidate, NLX-204, in two mouse models of depression. The peer-reviewed study, carried out in collaboration with the team of Dr. Karolina Pytka, at Jagiellonian University (Krakow, Poland) found that a single administration of NLX-204 was sufficient to completely abolish depression-like behaviors of mice subjected to chronic mild stress or to repeated administration of corticosterone, a pro-depressive substance. NLX-204 has previously been shown to posses strong antidepressant-like activity in naïve rats and 'biased agonist' activity at serotonin 5-HT1A receptors. The present study shows that its antidepressant properties are likely mediated by activation of specific cellular signaling mechanisms including phosphorylation of extracellular regulated kinase (ERK) and of cAMP response element-binding protein (CREB).

Depression is a major healthcare challenge affecting approximately 280 million people worldwide. Two-thirds of patients do not respond satisfactorily to current antidepressants, which require several weeks of administration before therapeutic onset, thus causing additional suffering for patients and their careers. Moreover, the COVID crisis has increased the incidence of depression and other affective disorders by nearly 30%.

Adrian Newman-Tancredi, CEO of Neurolixis, commented: “There is a large unmet medical need and market opportunity for an efficacious, rapid-acting and safe antidepressant to alleviate the suffering of millions of depressed patients. The promising results on NLX-204 suggest that it could constitute an innovative candidate for this indication and expand the Neurolixis 5-HT1A receptor 'biased agonist' development pipeline. ”

 The 5-HT_1A receptor biased agonist, NLX-204, shows rapid-acting antidepressant-like properties and neurochemical changes in two mouse models of depression.

Neurolixis CEO, Adrian Newman-Tancredi, PhD, DSc, was interviewed for an online event supported by the FRAXA Research Foundation and sponsored by WuXi AppTec. Dr. Newman-Tancredi commented Neurolixis' development of a novel treatment for Fragile X syndrome (FSX), a debilitating genetic orphan disease. Neurolixis is characterizing NLX-101, a small molecule Novel Chemical Entity, as a potential treatment for FXS. Recent data presented at the Gordon conference (Tuscany, Italy) showed that NLX-101 strongly protected transgenic Fragile X mice from audiogenic-induced seizures and lethality. Taken together with previous data on NLX-101's influence in animal models of mood and cognition, the new results suggest that it could constitute a promising treatment for several autism spectrum disorders, including FXS and Rett syndrome (see previous news). 

NLX-101 is in early Phase 1 clinical characterization and Neurolixis is looking for collaborative partnerships to support its development. 

See a video highlight of Adrian's interview on YouTube, together with a series of other interviews on Fragile X syndrome.
For a full transcript of the interview, see here.