Pipeline
Fast track designation by FDA
NYX-783
Description
NYX-783 is a novel, oral small molecule NMDA receptor modulator in development for the treatment of post-traumatic stress disorder, or PTSD.
Scientific Rationale
Dysregulation of NMDA receptor-mediated processes may underlie the development and / or persistence of PTSD.
- When recalling traumatic events, PTSD patients show reduced activation and altered connectivity of brain regions important for learning and memory
- Modulating NMDA receptors with NYX-783 to increase glutamatergic activity in these regions may act to enhance extinction learning and alleviate PTSD symptoms
Clinical Status
NYX-783 demonstrated clear signals of symptom reduction with a favorable tolerability profile in a Phase 2 exploratory study in patients with PTSD consisting of only 4 weeks of treatment with NYX-783
- NYX-783 has shown robust preclinical activity in fear extinction and other models relevant to psychiatric conditions, supporting its development as a potential therapeutic option for treating PTSD
- In a Phase 1 study, NYX-783 demonstrated a favorable safety and tolerability profile, linear and predictable pharmacokinetics, and ample CNS exposure
- NYX-783 was evaluated in a Phase 2 exploratory study in patients with PTSD
- NYX-783 50 mg exhibited a clinically meaningful change from baseline on CAPS-5 Total score
- NYX-783 50 mg demonstrated significantly greater improvement on percent change from baseline in the CAPS-5 domain cluster scores for Arousal & Reactivity and Negative Cognitions & Mood compared to placebo
- The U.S. Food and Drug Administration has granted Fast Track designation to the development of NYX-783 for the treatment of PTSD
- To learn more about the clinical studies of NYX-783, see our Clinical Studies page
NYX-458
Description
NYX-458 is a novel, oral, small molecule NMDA receptor modulator in development for the treatment of cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies.
Scientific Rationale
Lewy body dementia, consisting of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) comprises 15–20% of cases of dementia.
- Both Parkinson’s disease cognitive impairment and dementia with Lewy bodies share a common disease pathology
- Increased deposits of the protein alpha synuclein in the brain lead to a reduction in NMDA receptor expression and in turn, bring about problems with cognitive functioning
- NYX-458 has the potential to treat cognitive symptoms by modulating NMDA receptors to overcome the dysfunction caused by elevated levels of alpha synuclein in the brain
Clinical Status
NYX-458 is under evaluation in a first-in-patient Phase 2 study in cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies.
- NYX-458 demonstrated robust preclinical activity in numerous rodent models of cognitive function
- Striking reversal of cognitive deficits was observed following administration of NYX-458 in a highly-translatable non-human primate model of Parkinson’s disease
- Phase 1 study demonstrated favorable safety, PK, and CNS exposure in humans
- The Phase 2 study will evaluate the safety and tolerability of NYX-458 in people with mild cognitive impairment and mild dementia associated with Parkinson’s disease and dementia with Lewy bodies, and measure activity across multiple neurocognitive assessments
- To learn more about the clinical studies of NYX-458, please see our Clinical Studies page