NYX-458 / Aptinyx - LARVOL DELTA

New advances in small molecule drugs targeting NMDA receptors. (PubMed, Acta Pharmacol Sin) - "Among various therapeutic indications, depression has emerged as an especially active area of investigation, with mechanistically diverse compounds ranging from broad-spectrum channel blockers (ketamine, dextromethorphan, esmethadone) to glycine site modulators (rapastinel, 4-chlorokynurenine, D-cycloserine) and allosteric modulators (apimostinel, zelquistinel), progressing through clinical pipelines. Beyond depression, NMDA receptor-targeted drug discovery is also advancing in other challenging CNS disorders, including neurodegenerative diseases (salzanemdor, NYX-458), pain (NYX-2925), epilepsy (radiprodil), and stroke (nelonemdaz, NP10679). Collectively, these developments reflect the maturation of NMDA receptor pharmacology and reaffirm the broad therapeutic potential of NMDA receptor modulation, while highlighting promising directions for future drug discovery."

Journal • Review • Cardiovascular • CNS Disorders • Depression • Epilepsy • Mental Retardation • Pain • Psychiatry

Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches. (PubMed, Medicina (Kaunas)) - "Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Movement Disorders • Parkinson's Disease • FGF21

Lewy Body Dementia: An Overview of Promising Therapeutics. (PubMed, Curr Neurol Neurosci Rep) - "We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Aptinyx Reports Results from Phase 2 Study of NYX-458 in Cognitive Impairment Associated with Parkinson's Disease and Dementia with Lewy Bodies and Provides Pipeline and Corporate Update (Businesswire) - P2 | N=99 | NCT04148391 | Sponsor: Aptinyx | "Aptinyx Inc...announced results from a Phase 2 clinical study evaluating the effects of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. Across the overall study population, NYX-458 did not demonstrate clinically meaningful improvements over placebo on the study’s efficacy endpoints. The results do not support further development of NYX-458 by the company....The results overall do not support further advancement of the development program by Aptinyx. The company intends to undertake cost-cutting measures to preserve capital and support the exploration of strategic alternatives..."

Discontinued • P2 data • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Parkinson's Disease

NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's Disease or Lewy Body Dementia (Cognition, Memory, Attention, Thinking) (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Aptinyx | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Aptinyx Completes Enrollment in Phase 2 Study of NYX-458 in Cognitive Impairment Associated with Parkinson’s Disease and Dementia with Lewy Bodies (Businesswire) - "Aptinyx...today announced the completion of enrollment of 99 patients in the company’s ongoing Phase 2 study of NYX-458 in cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. Patients recently enrolled in the study are completing the 12-week treatment period and 30-day safety follow-up period. The company expects to report results from the study in 1Q 2023."

Enrollment closed • P2 data • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Parkinson's Disease

An overview of the active clinical trials for Parkinson's disease psychosis. (PubMed, Neurodegener Dis Manag) - "Tweetable abstract An overview of the active clinical trials for Parkinson's disease psychosis. In this article, we review the drugs currently undergoing clinical testing for Parkinson's disease psychosis and offer some perspectives on the treatment of the condition."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Aptinyx Reports Fourth Quarter and Full Year 2021 Results and Highlights (Businesswire) - "Aptinyx Inc...today reported financial results for the fourth quarter and full year 2021 and provided updates across the company’s pipeline of novel NMDA receptor modulators....2022 Upcoming Milestones: Data readout from Phase 2b study of NYX-2925 in patients with painful DPN – April 2022...Data readout from Phase 2b study of NYX-2925 in patients with fibromyalgia – early to mid 3Q 2022...Data readout from exploratory Phase 2 study of NYX-458 in cognitive impairment – late 2022 or 1Q 2023..."

P2 data • P2b data • CNS Disorders • Cognitive Disorders • Diabetic Neuropathy • Fibromyalgia • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain

Aptinyx Highlights Key Goals and Anticipated Development Milestones for 2022 (Businesswire) - "Aptinyx Inc. today provided a corporate update and highlighted development milestones anticipated in 2022....NYX-2925 for chronic pain – Phase 2b readouts expected in 2Q and mid-year 2022....The company’s Phase 2b study of NYX-2925 in 300 patients with fibromyalgia is on track to report results in mid 2022....NYX-458 for cognitive impairment – Phase 2 readout expected in 2H 2022....Enrollment is progressing in an exploratory Phase 2 study of NYX-458 in 100 patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. The company anticipates reporting data from the study in the second half of 2022."

Enrollment status • P2 data • P2b data • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Pain • Parkinson's Disease

THE NMDA RECEPTOR POSITIVE ALLOSTERIC MODULATOR NYX-458 RESCUES AGE-RELATED SYNAPTIC DYSFUNCTION VIA CAMKIIΒ-MEDIATED SIGNALING IN THE PREFRONTAL CORTEX AND HIPPOCAMPUS (ADPD 2022) - "NYX-458 enhances synaptic plasticity mechanisms associated with hippocampal-dependent learning and memory and induces changes within the PFC as part of an interconnected network. These data support the development of NYX-458 for the treatment of cognitive decline."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Aptinyx Hosts Virtual Portfolio Review Event to Showcase NYX-2925 in Chronic Pain and Provide Update on Clinical Development Programs (Businesswire) - "Aptinyx Inc...will host a virtual portfolio review event today beginning at 10:00 a.m. ET. Presented in a live webcast format, the company will discuss its approach to the development of novel NMDA receptor modulators and review its pipeline of four clinical development programs, with particular focus on NYX-2925 in chronic pain....Aptinyx expects to report data from the Phase 2b painful DPN study in April or early May and anticipates reporting data from the Phase 2b fibromyalgia study in mid-2022....NYX-458 is currently under evaluation in an exploratory Phase 2 study in patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. The company expects to report data from this study in 4Q 2022 or 1Q 2023."

Clinical • P2 data • P2b data • CNS Disorders • Cognitive Disorders • Diabetic Neuropathy • Fibromyalgia • Musculoskeletal Pain • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain

Aptinyx Reports Third Quarter 2021 Financial Results and Recent Highlights (Businesswire) - “Clinical study enrollment updates: In October, the company announced the completion of enrollment in the company’s ongoing Phase 2b study of NYX-2925 for the treatment of painful diabetic peripheral neuropathy (DPN)…and the company expects to report results from the study in early to mid 2Q 2022….Enrollment progressing in Phase 2b study of NYX-2925 in patients with fibromyalgia – The study is expected to read out in mid 2022. Enrollment progressing in exploratory Phase 2 study of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies –The study is expected to read out in 2H 2022….Research and development expenses were $16.3 million for the three months ended September 30, 2021...The increase in R&D expenses was primarily driven by costs associated with enrollment activities in the company’s two ongoing Phase 2b studies of NYX-2925 in chronic pain.”

Commercial • P2 data • CNS Disorders • Cognitive Disorders • Diabetic Neuropathy • Fibromyalgia • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain

Aptinyx Reports First Quarter 2021 Financial Results and Highlights (Businesswire) - "...Aptinyx announced the recommencement of its exploratory Phase 2 study of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease and dementia with Lewy bodies. Enrollment in this study had previously been suspended due to the escalation of the COVID-19 pandemic...The company expects to enroll approximately 100 patients in the study and anticipates reporting data from the study in the second half of 2022."

Enrollment status • P2 data • CNS Disorders • Cognitive Disorders • Lewy Body Disease • Parkinson's Disease

Treatment of Parkinson's Disease with Cognitive Impairment: Current Approaches and Future Directions. (PubMed, Behav Sci (Basel)) - "The only recommended treatment for PDD currently is rivastigmine, a cholinesterase inhibitor. Donepezil and galantamine-other cholinesterase inhibitors-are possibly useful...Drug repurposing (atomoxetine, levodopa, insulin, atomoxetine for PD-MCI; ambroxol and ceftriaxone for PDD) and novel medications (SYN120, GRF6021, NYX-458 for PD-MCI; ANAVEX2-73, LY3154207, ENT-01, DAAOI-P for PDD) currently have insufficient evidence. There is growing research supporting exercise in the treatment of PD-MCI, but most non-pharmacological approaches have insufficient evidence for use in PD-MCI (cognitive rehabilitation, deep brain stimulation, transcranial direct current stimulation, transcranial ultrasound, vestibular nerve stimulation) and PDD (cognitive intervention, deep brain stimulation, transcranial alternating current stimulation, transcranial ultrasound, temporal blood brain barrier disruption). Research is needed for both disease-modifying and symptomatic treatments in PD..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Movement Disorders • Parkinson's Disease

Aptinyx Recommences Phase 2 Study of NYX-458 in Patients with Cognitive Impairment Associated with Parkinson’s Disease Dementia and Dementia with Lewy Bodies (Businesswire) - "Three Phase 2 data readouts expected over the next 12 to 18 months across the company’s clinical development pipeline...Aptinyx Inc....announced that it has recommenced patient screening in a Phase 2 study of NYX-458 in patients with mild cognitive impairment and mild dementia associated with Parkinson’s disease and dementia with Lewy bodies. The company anticipates reporting data from this study in the second half of 2022."

P2 data • Trial status • CNS Disorders • Dementia • Lewy Body Disease • Parkinson's Disease

NYX-458 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's Disease or Lewy Body Dementia (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Aptinyx; Active, not recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Aptinyx Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update (Businesswire) - "Recommencement of patient screening in Phase 2a study of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease or dementia with Lewy bodies – First week of April 2021...Data readout from Phase 2b study of NYX-2925 in patients with painful DPN– 1H 2022. Data readout from Phase 2a study of NYX-458 in cognitive impairment – 2H 2022."

Enrollment status • P2a data • CNS Disorders • Cognitive Disorders • Parkinson's Disease

Aptinyx Reports Third Quarter 2020 Financial Results and Recent Highlights (Businesswire) - "Strengthened the company’s financial position through the completion of a $48.3 million common stock offering....The company’s current cash balance, inclusive of the net proceeds from the offering, is expected to provide financial support into 2023 and enable completion of multiple ongoing Phase 2 clinical studies. Expected Upcoming Milestones: Recommencement of Phase 2b clinical study of NYX-2925 in patients with painful diabetic peripheral neuropathy – 4Q 2020; Recommencement of Phase 2 exploratory clinical study of NYX-458 in patients with cognitive impairment associated with Parkinson’s disease – 1Q 2021;...Reporting of data from Phase 2b clinical study of NYX-2925 in patients with fibromyalgia – 1H 2022; Reporting of data from Phase 2b clinical study of NYX-2925 in patients with painful DPN – 1H 2022."

Financing • P2b data • Trial initiation date • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain

Aptinyx Announces Pricing of Public Offering of Common Stock (Businesswire) - "Aptinyx Inc....today announced the pricing of its public offering of 14,000,000 shares of its common stock at a public offering price of $3.00 per share....Aptinyx intends to use the net proceeds received from the offering to advance the development of its novel NMDA receptor modulators, including NYX-2925, NYX-783, and NYX-458, in development for chronic pain, PTSD, and cognitive impairment, respectively, and for working capital and other general corporate purposes."

Financing • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain • Post-traumatic Stress Disorder

Aptinyx reports first quarter 2020 financial results and highlights (GlobeNewswire) - "Achieved over 90% of target patient enrollment to date in Phase 2 exploratory study of NYX-783 in post-traumatic stress disorder (PTSD)....In March, Aptinyx announced the temporary suspension of new patient enrollment in its Phase 2 studies in painful diabetic peripheral neuropathy (DPN), fibromyalgia, and Parkinson’s disease cognitive impairment....Upcoming Milestones: Reporting data from Phase 2 exploratory, first-in-patient study of NYX-783 in patients with PTSD – late 2020. Aptinyx anticipates providing updated guidance on the timing of data reporting for the following clinical studies at a future date: Phase 2 study of NYX-2925 in painful DPN. Phase 2 study of NYX-2925 in fibromyalgia. Phase 2 exploratory study of NYX-458 in Parkinson’s disease cognitive impairment."

Clinical • Enrollment status • P2 data • CNS Disorders • Mood Disorders • Musculoskeletal Pain • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain • Post-traumatic Stress Disorder • Psychiatry

Aptinyx reports fourth quarter and full year 2019 financial results and provides corporate update (GlobeNewswire, Aptinyx Inc.) - "NYX-458 exploratory Phase 2 study in Parkinson’s disease cognitive impairment: On March 27, 2020, Aptinyx temporarily suspended enrollment of new patients in this study....Aptinyx anticipates updating guidance around the expected timing of reporting data from this study at a future date following the recommencement of enrollment....This exploratory study evaluates the safety of NYX-458 in patients with Parkinson’s MCI, as well as its effects on cognitive performance using multiple measures across various cognitive domains."

Enrollment status • Trial status

A Study to Evaluate NYX-458 in Subjects With PD-MCI (clinicaltrials.gov) - P2; N=135; Active, not recruiting; Sponsor: Aptinyx; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Aptinyx announces publication of data in movement disorders demonstrating reversal of cognitive deficits with NYX-458 in primate model of Parkinson’s disease (GlobeNewswire) - "Aptinyx Inc....today announced a publication in Movement Disorders detailing data on its novel NMDAr modulator, NYX-458. The data demonstrate that administration of NYX-458 resulted in a reversal of cognitive deficits in a non-human primate model of Parkinson’s disease; NYX-458 is currently under evaluation in a Phase 2 study in patients with mild cognitive impairment associated with Parkinson’s disease."

Preclinical • Trial status

NYX-458 improves cognitive performance in a primate Parkinson's disease model. (PubMed, Mov Disord) - "NYX-458 provides benefit in specific domains known to be impaired in PD in a dopamine depletion model of PD-like cognitive impairment. These data support the continued evaluation of NYX-458 as a potential therapeutic for cognitive decline in PD."

Journal

Aptinyx Announces Closing of Public Offering of Common Stock and Full Exercise of Underwriters’ Option (GlobeNewswire, Aptinyx Inc.) - "Aptinyx intends to use the net proceeds received from the offering to advance the preclinical and clinical development of its novel NMDA receptor modulators, including NYX-2925, NYX-783, and NYX-458, in development for chronic pain, PTSD, and cognitive impairment, respectively, and for working capital and other general corporate purposes."

Financing