NYX-783 / Aptinyx - LARVOL DELTA

The NMDAR positive allosteric modulator NYX-783 selectively blocks opioid withdrawal conditioned place aversion in mice. (PubMed, bioRxiv) - "Currently approved medications for OUD include the opioid agonists methadone and buprenorphine, and the opioid antagonist naltrexone. We observed a significant improvement in aversion scores in female mice treated with NYX-783, and a trending significant improvement in males. This suggests a potential therapeutic use for NYX-783 in reducing the negative state of withdrawal that can drive relapse in OUD."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry • Substance Abuse

Pharmacokinetic and Electrocardiographic Drug-Drug Interactions between NYX-783 and Oxycodone among Recreational Users of Opioids: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study (CPDD 2025) - "In addition to previously documented safety of NYX, preliminary results ruled out DDI on ECG features and showed DDI in which 30 mg dose of oxycodone is associated with higher levels of NYX 150."

Clinical • P1 data • PK/PD data • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed

Trial completion • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Yale University | Trial primary completion date: Aug 2024 ➔ Dec 2024

Combination therapy • Trial primary completion date • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Yale University | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Yale University | Trial completion date: Mar 2024 ➔ Oct 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Trial completion date • Trial primary completion date • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Yale University | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Substance Abuse

Safety and Efficacy of 50 mg NYX-783 QD vs. Placebo in PTSD (clinicaltrials.gov) - P2/3 | N=121 | Terminated | Sponsor: Aptinyx | N=300 ➔ 121 | Trial completion date: Dec 2023 ➔ Mar 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Mar 2023; company decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Safety and Efficacy of 50 mg NYX-783 QD vs. Placebo in PTSD (clinicaltrials.gov) - P2/3 | N=300 | Active, not recruiting | Sponsor: Aptinyx | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: Yale University | Initiation date: Jan 2023 ➔ Apr 2023

Combination therapy • Trial initiation date • Substance Abuse

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: Yale University | Trial completion date: Sep 2023 ➔ Mar 2024 | Initiation date: Oct 2022 ➔ Jan 2023 | Trial primary completion date: Sep 2023 ➔ Dec 2023

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Substance Abuse

Preclinical evaluation of the NMDAR positive allosteric modulator NYX-783 for opioid use disorder (Neuroscience 2022) - "Currently approved medications for OUD include the opioid agonists methadone and buprenorphine, and the opioid antagonist naltrexone. We observed a significant reduction in place aversion in the NYX-783 treated mice. These data suggest a potential therapeutic use for NYX-783 in reducing the negative state of withdrawal that can drive relapse in OUD."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry • Substance Abuse

Positive allosteric modulator of the NMDA receptor, NYX-783, reverses repeated stress-induced reduction of exploration and reduces fear to unpredictable threats in rats (Neuroscience 2022) - P2 | "After stress there was a dose-dependent increase in time spent in the open arm (P0.05, unpaired t-test, t=0.52, df=22). Overall, our results show that NYX-783 at 30 mg/kg reverses repeated stress-induced reduction of exploration, acutely reduces fear to unpredictable threats, and demonstrates pharmacotherapeutic potential for PTSD."

Preclinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

"$APTX Clinical Evaluation of Aptinyx';s NYX-783 for Treatment of Opioid Use Disorder to Be Funded by $5.6 Million NIH Grant https://t.co/LXPaT8oX70" (@stock_titan)

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse

Clinical Evaluation of Aptinyx’s NYX-783 for Treatment of Opioid Use Disorder to Be Funded by $5.6 Million NIH Grant (Businesswire) - "Aptinyx Inc....announced the finalization of a $5.6 million grant under the National Institutes of Health (NIH) Helping to End Addiction Long-term (HEAL) Initiative, supporting the development of NYX-783 for the treatment of opioid use disorder (OUD). NYX-783 is an NMDA receptor positive allosteric modulator also in Phase 2b development by Aptinyx for the treatment of post-traumatic stress disorder (PTSD)....'The data generated from our preclinical studies in models of OUD have laid a strong foundation for the potential of NYX-783 in promoting relapse prevention among patients with opioid use disorder. With the support of the NIDA grant, we look forward to translating these findings to clinical benefit in humans through this Phase 1 development program.'"

Financing • Preclinical • Trial status • CNS Disorders • Post-traumatic Stress Disorder

Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: Yale University

Combination therapy • New P1 trial • Substance Abuse

NYX-783, a Novel Positive Allosteric Modulator of the N-Methyl D-Aspartate receptor, Increases NMDAR-Mediated Signaling in the Infralimbic Prefrontal Cortex to Facilitate Extinction Learning in PTSD-Relevant Rodent Models (SOBP 2022) - "These findings provide a putative mechanism of action for NYX-783 for the alleviation of PTSD-relevant symptoms. NYX-783 is currently in clinical development for the treatment of PTSD and showed clinically meaningful improvements in multiple parameters for assessing PTSD symptoms, including the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)after only 4 weeks."

Preclinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF

The Role of NMDA Receptor Function in Relation to Prefrontal Cortex Activity in Posttraumatic Stress Disorder (SOBP 2022) - "A summary of several studies on network-based alterations in PTSD and the role of the network effects of the NMDA antagonist ketamine in treating trauma -related psychopathology will be provided. Finally, preclinical data on the effect of the NMDA positive allosteric modulator (NYX-783) in PTSD-relevant animal models will be shared. In conclusion, NMDA receptor modulation emerges as a putative target for the treatment of PTSD, with complex yet promising initial findings."

CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

NYX-783, a Novel Positive Allosteric Modulator of the N-Methyl D-Aspartate Receptor, Facilitates Extinction Learning in PTSD-Relevant Mouse Models (APA 2022) - "In a completed Phase II clinical study, subjects receiving NYX-783 showed clinically meaningful improvements in multiple parameters used to assess PTSD symptoms, including the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), after only 4 weeks of treatment. This study was supported by Aptinyx Inc."

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • BDNF

Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. (PubMed, Mol Psychiatry) - "These results elucidate the cellular targets of NYX-783 and the molecular mechanisms underlying the inhibition of spontaneous recovery. These preclinical findings support the hypothesis that NYX-783 may have therapeutic potential for PTSD treatment and may be particularly useful for inhibiting spontaneous recovery."

Journal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF

Safety and Efficacy of 50 mg NYX-783 QD vs. Placebo in PTSD (clinicaltrials.gov) - P2/3; N=300; Recruiting; Sponsor: Aptinyx

Clinical • New P2/3 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

[VIRTUAL] A Randomized, Placebo-Controlled, Double-Blind Study of NYX-783 in Patients With Post-traumatic Stress Disorder (SOBP 2021) - "NYX-783 demonstrated promising results for the treatment of PTSD."

Clinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

[VIRTUAL] A Randomized, Placebo-Controlled, Double-Blind Study of NYX-783 in Patients With Post-traumatic Stress Disorder (SOBP 2021) - "NYX-783 demonstrated promising results for the treatment of PTSD."

Clinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

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

Safety and Efficacy of NYX-783 in Subjects With Post-Traumatic Stress Disorder (clinicaltrials.gov) - P2; N=160; Completed; Sponsor: Aptinyx; Active, not recruiting ➔ Completed; Trial completion date: Dec 2020 ➔ Aug 2020

Trial completion • Trial completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry