Pipeline
Fast track designation by FDA
NYX-2925
Description
NYX-2925 is a novel, oral small molecule NMDA receptor modulator in development for the treatment of chronic pain.
Scientific Rationale
Dysregulation of glutamatergic circuits in the brain is involved in the development of centralized chronic pain.
- Glutamate is the primary excitatory neurotransmitter in the brain and a co-ligand for the NMDA receptor
- NYX-2925 modulates NMDA receptors to target aberrant central pain processing
- Optimal modulation of these receptors enhances synaptic plasticity, restoring and normalizing the communication between neural cells
Clinical Status
NYX-2925 is in late stage clinical development across two chronic pain indications – Painful Diabetic Peripheral Neuropathy and Fibromyalgia.
- Strong preclinical evidence showing robust, long-lasting effect across various models of neuropathic pain
- Completed multiple Phase 1 studies which demonstrated favorable safety and tolerability, linear and predictable pharmacokinetics, and ample CNS exposure
- NMDA receptor pathway activity demonstrated through Phase 1 EEG studies
- NYX-2925 showed significant activity on biomarkers of centralized pain processing in a Phase 2 neuroimaging study in patients with fibromyalgia
- Evidence of pain reduction demonstrated in Phase 2 study in patients with painful DPN
- NYX-2925 has been granted Fast Track designation for the treatment of neuropathic pain associated with Diabetic Peripheral Neuropathy by the U.S. Food and Drug Administration
- To learn more about the clinical studies of NYX-2925, see our Clinical Studies page
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; A registration-supportive study evaluating NYX-783 in patients with PTSD is expected to begin in 2021.
- 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.
Scientific Rationale
NMDA receptors are critical to learning and memory processes and their dysregulation has been implicated across numerous conditions involving cognitive impairment.
- Approximately half of all people with Parkinson’s suffer from cognitive impairment
- It is believed that the loss of dopaminergic neurons and the associated downstream changes including dysregulation and dysfunction of NMDA receptors, leads to impairments across multiple cognitive domains
- NYX-458 has the potential to treat these cognitive symptoms by modulating NMDA receptor function to overcome the dysregulation caused by the loss of dopaminergic neurons
Clinical Status
NYX-458 is under evaluation in a first-in-patient Phase 2 study in cognitive impairment associated with Parkinson’s disease.
- 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 studies 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 Parkinson’s disease, and measure its activity across multiple efficacy endpoints related to cognitive impairment
- To learn more about the clinical studies of NYX-458, please see our Clinical Studies page