Favorable overall safety, tolerability, and pharmacokinetic profile—no serious adverse events reported across wide dose range
Achieved ample CNS exposure consistent with exposure observed at preclinically efficacious doses
Expect to initiate Phase 2a study in patients with cognitive impairment associated with Parkinson’s disease in 2H 2019
“We are very encouraged by the favorable safety and tolerability profiles we continue to observe with compounds generated from our platform,” said
In the randomized, placebo-controlled study, which included 62 healthy volunteers, single and multiple ascending oral doses of NYX-458 were evaluated across a 20-fold dose range—10 mg to 200 mg. Across the study, including in a cohort of elderly volunteers, NYX-458 demonstrated a favorable safety and tolerability profile with no serious adverse events reported and no adverse events leading to discontinuation. Only two adverse events—one headache and one case of nausea—in the study were considered possibly related to NYX-458 and both were characterized as mild.
Further, NYX-458 demonstrated a dose-proportional pharmacokinetic profile and no meaningful accumulation was observed with seven daily doses. The highly predictable nature of this pharmacokinetic profile enables accurate dose selection to achieve appropriate therapeutic exposure in clinical development. As evaluated through cerebral spinal fluid drug concentration, NYX-458 demonstrated CNS exposure in line with that observed at preclinically efficacious doses. CSF exposure levels were approximately 15% of the plasma concentration, similar to observations in preclinical studies.
NYX-458 is a novel oral NMDA receptor modulator currently in clinical development for the treatment of cognitive impairment associated with Parkinson’s disease. NYX-458 has been shown to reverse cognitive deficits in non-human primates in a model that is highly translatable to Parkinson’s disease in humans. Additionally, NYX-458 has been shown to improve cognitive performance across various rodent models of disease. In a Phase 1 clinical study, NYX-458 exhibited a favorable safety and tolerability profile across a wide dose range and achieved CNS exposure in line with exposure observed with efficacious preclinical dose levels.
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the company’s business plans and objectives, including future plans or expectations for the company’s product candidates, therapeutic effects of the company’s product candidates, expectations regarding the design, implementation, timing, and success of its current and planned clinical studies, and expectations regarding its uses and sufficiency of capital. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the company’s product candidate development activities and planned clinical studies; the company’s ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in
Source: Aptinyx Inc.