sunobinop (IMB-115) / Shionogi, Purdue - LARVOL DELTA

Efficacy and safety of a selective partial agonist for nociception/orphanin-FQ peptide (NOP) receptors in patients with insomnia disorder. (PubMed, Br J Clin Pharmacol) - "In this Phase 1 study of 30 patients, sunobinop was well tolerated by patients, with no study discontinuation due to AEs. Doses were identified that had a beneficial effect on sleep measures without eliciting next-day residual effects (<3 mg). These data suggest that sunobinop has the potential to be developed as a therapeutic option for the treatment of sleep disturbances, including DSM-5 insomnia; however, larger confirmatory studies are warranted."

Clinical • Journal • CNS Disorders • Insomnia • Mental Retardation • Psychiatry • Sleep Disorder

Study of Sunobinop on Alcohol Consumption in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Imbrium Therapeutics | Trial completion date: Jul 2025 ➔ Mar 2026 | Trial primary completion date: Jul 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Study of Sunobinop on Craving in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: Imbrium Therapeutics | Recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol)

In vitro pharmacological evaluation of the novel NOP receptor partial agonist sunobinop. (PubMed, Biochem Pharmacol) - "Notably, it demonstrated competitive antagonism in the NOP - β-Arrestin 2 recruitment and ex vivo electrically stimulated mouse Vas Deferens, assays characterized by low amplification. The findings reported here confirm and extend the characterization of sunobinop as a tool for studying NOP receptor pharmacology providing new insights into its mode of action, relevant to its clinical evaluation."

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder • ARRB1

Imbrium Therapeutics Achieves Last Patient Last Visit in Clinical Trial of Potential Treatment for Interstitial Cystitis/Bladder Pain Syndrome (Businesswire) - "Imbrium Therapeutics...has achieved last patient last visit in its Phase 1b study of the investigational drug sunobinop as a potential treatment for interstitial cystitis/bladder pain syndrome (IC/BPS). IC/BPS is a chronic painful and debilitating urologic disorder that negatively affects patients’ quality of life and can lead to radical lifestyle and behavioral modifications....Forty-seven female patients with IC/BPS were enrolled in this multicenter, randomized, double-blind, placebo-controlled, crossover study. The study was designed to assess impact of once-a-day sunobinop taken at bedtime for 6 weeks on key disease symptoms, such as bladder pain and discomfort as well as urinary urgency and frequency, in subjects with IC/BPS compared to placebo."

Enrollment closed • Interstitial Cystitis • Pain

Study of Sunobinop on Craving in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Imbrium Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

Study of V117957 in Interstitial Cystitis/Bladder Pain Syndrome (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Imbrium Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Jan 2025 | Trial primary completion date: Jun 2026 ➔ Jan 2025

Trial completion • Trial completion date • Trial primary completion date • Interstitial Cystitis • Musculoskeletal Pain • Pain

Study of Sunobinop on Craving in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Imbrium Therapeutics | Initiation date: Sep 2024 ➔ Feb 2025

Trial initiation date • Addiction (Opioid and Alcohol)

Study of V117957 in Interstitial Cystitis/Bladder Pain Syndrome (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Imbrium Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Interstitial Cystitis • Musculoskeletal Pain • Pain

Study of Sunobinop on Alcohol Consumption in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Imbrium Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

Evaluation of sunobinop for next-day residual effects in healthy participants. (PubMed, Front Pharmacol) - "No deaths occurred during the study or discontinuations due to an AE. Overall, a nighttime oral dose of sunobinop up to 2 mg was safe and generally well tolerated in healthy participants with limited next-day residual effects that were consistent with other sedative/hypnotic drugs."

Clinical • Journal • CNS Disorders • Insomnia • Sleep Disorder

Study of Sunobinop on Craving in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Imbrium Therapeutics

New P2 trial • Addiction (Opioid and Alcohol)

Study of Sunobinop on Alcohol Consumption in Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Imbrium Therapeutics

New P2 trial • Addiction (Opioid and Alcohol)

Study of V117957 in Overactive Bladder Syndrome (clinicaltrials.gov) - P1 | N=51 | Completed | Sponsor: Imbrium Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ May 2024 | Trial primary completion date: Dec 2024 ➔ May 2024

Trial completion • Trial completion date • Trial primary completion date • Overactive Bladder

Study of V117957 in Overactive Bladder Syndrome (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Imbrium Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Overactive Bladder

Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "Most treatment-emergent adverse events (TEAEs) were mild in severity; 1 severe TEAE occurred and all TEAEs resolved by the end of the studies. Sunobinop was generally well-tolerated and safe across the range of doses evaluated and presents a clinical profile suitable for continued development."

Clinical • Journal • PK/PD data

Study of V117957 in Interstitial Cystitis/Bladder Pain Syndrome (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Imbrium Therapeutics

New P1 trial • Interstitial Cystitis • Musculoskeletal Pain • Pain

The nociceptin/orphanin-FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia. (PubMed, J Clin Invest) - No abstract available

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder

Study of V117957 in Overactive Bladder Syndrome (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Imbrium Therapeutics

New P1 trial • Overactive Bladder

Sunobinop: A novel selective partial agonist at nociception/orphanin-FQ peptide (NOP) with sleep promoting and wake suppressing actions (WSS 2023) - No abstract available

S20: The N/OFQ – NOP receptor system and its putative roles in nociception, analgesia, mood disorders and sleep (WSS 2023) - "Garth Whiteside will then present the discovery and development of Sunobinop as the first selective NOP agonist in development for sleep disorders. Both the preclinical profile and results from clinical studies in individuals with primary insomnia, as well as patients experiencing insomnia during recovery from alcohol use disorder, will be discussed.Learning objectivesUpon completion of this CME activity, participants will be able to: · Describe the nociception/orphanin FQ (N/OFQ) – NOP receptor system, its underlying neurobiology, and its intracellular signaling mechanisms· Identify some of the physiological functions and disorders in which the N/OFQ – NOP system has been implicated· List some potential therapeutic uses of NOP ligands· Recognize the evidence that supports a potential role for this system in sleep/wake"

Addiction (Opioid and Alcohol) • CNS Disorders • Cognitive Disorders • Insomnia • Mood Disorders • Pain • Psychiatry • Sleep Disorder

Results From a Phase 2, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Parallel-Group Study of Sunobinop in Subjects who are Experiencing Insomnia During Recovery From Alcohol Use Disorder (CPDD 2023) - "Sunobinop 1mg and 2mg administered at bedtime resulted in a significant and clinically meaningful reduction in WASO as measured by polysomnography at both timepoints. Given the association between sleep disturbances and AUD and the potential role for NOP agonists 1 in reducing the acquisition, expression, and reinstatement of the reinforcing effects of alcohol in animals, further investigation of the effect of sunobinop on sleep and alcohol craving in the setting of AUD is warranted."

Clinical • P2 data • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Insomnia • Sleep Disorder

EFFECTS OF SUNOBINOP (V117957) IN A MODEL OF ACUTE CYSTITIS INDUCED BY CYCLOPHOSPHAMIDE (AUA 2023) - "Source of Funding : Imbrium Therapeutics L.P. a subsidiary of Purdue Pharmaceuticals L.P. INTRODUCTION AND OBJECTIVE: Interstitial Cystitis (IC) is a chronic urological disorder characterized by pain urinary urgency, frequency and nocturia. The positive control, ibuprofen, significantly decreased pain responses, as compared to vehicle in an acute model of CYP induced IC. Likewise, sunobinop was significantly anti-nociceptive. As such this data suggests sunobinop has potential utility in treatment of pain associated with IC."

Interstitial Cystitis • Pain • Urology

Safety, Tolerability and Efficacy Study of V117957 in Subjects With Insomnia Associated With Alcohol Cessation (clinicaltrials.gov) - P2; N=114; Completed; Sponsor: Imbrium Therapeutics; Active, not recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Insomnia • Sleep Disorder

Safety, Tolerability and Efficacy Study of V117957 in Subjects With Insomnia Associated With Alcohol Cessation (clinicaltrials.gov) - P2; N=150; Active, not recruiting; Sponsor: Imbrium Therapeutics; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Insomnia • Sleep Disorder