osanetant (ACER-801) / Sanofi, Zevra Therap - LARVOL DELTA

The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats. (PubMed, Int J Neuropsychopharmacol) - "Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs."

Journal • Preclinical

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P1/2 | N=49 | Completed | Sponsor: Acer Therapeutics Inc. | Phase classification: P2a ➔ P1/2

Phase classification

Systematic review of neurokinin-3 receptor antagonists for the management of vasomotor symptoms of menopause. (PubMed, Menopause) - "Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS."

Journal • Review • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Pain

POSH-MAP: Pilot of Osanetant to Reduce Severity of Hot Flashes in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: University of Kansas Medical Center | N=10 ➔ 0 | Trial completion date: Nov 2025 ➔ Oct 2023 | Recruiting ➔ Withdrawn | Trial primary completion date: Nov 2024 ➔ Sep 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Neutropenia • Oncology • Prostate Cancer

PORT-MAP: Pilot of Osanetant to Reduce Testosterone in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: University of Kansas Medical Center | N=10 ➔ 1 | Trial completion date: Nov 2025 ➔ Nov 2023 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Sep 2023; Development of the drug program has been discontinued

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Neutropenia • Oncology • Prostate Cancer

Activation of neurokinin-III receptors modulates human atrial TASK-1 currents. (PubMed, J Mol Cell Cardiol) - "Heterologously expressed human TASK-1 channels are inhibited by neurokinin-III receptor activation in a DAG dependent fashion. Patch-clamp measurements, performed on human atrial cardiomyocytes suggest that the atrial-specific effects of neurokinin-III receptor activation on cardiac excitability are predominantly mediated via TASK-1 currents."

Journal • Atrial Fibrillation • Cardiovascular

Role of Projections from central amygdala to the posterolateral bed nucleus of stria terminalis on sex differences in fear memory (ECNP 2023) - "After surgery, both proestrus female mice and male mice underwent the cued-fear acquisition paradigm and 30 minutes after CeA-BNSTpl (central amygdala to the posterolateral bed nucleus of stria terminalis) projections were chemogenetically silenced by a dose of Clozapine-N-Oxide (CNO) or vehicle...The aforementioned proestrus female and male mice received an osanetant injection 30 minutes after Fear acquisition...What is more, pharmacogenetic temporal inhibition of the Tac2-CeA to BNSTpl projections resulted in increased estradiol levels in females and reduced testosterone in males. In brief, our data uncover novel mechanisms of sex hormones and differences in neuronal projects of fear memory."

CNS Disorders • Post-traumatic Stress Disorder

Effect of neurokinin 3 receptor antagonism on fear extinction after stress (ECNP 2023) - "Systemic administration of Osanetant after IMO showed a decreased freezing compared to vehicle (Sex*Treatment f(1,1)= 4.619, p < 0.05) in females during the first day of fear extinction, 24 hours after fear acquisition. We conclude that Tac2- pathway inactivation with Osanetant has improved fear extinction in females after acute stress immobilisation and could be potentially used to rescue fear extinction impairment after a traumatic event."

CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=49 | Completed | Sponsor: Acer Therapeutics Inc. | Active, not recruiting ➔ Completed

Trial completion

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Active, not recruiting | Sponsor: Acer Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Recruiting | Sponsor: Acer Therapeutics Inc. | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial primary completion date

PORT-MAP: Pilot of Osanetant to Reduce Testosterone in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Kansas Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Prostate Cancer • CAST

Acer Therapeutics Announces Initiation of Two Investigator-Sponsored Trials of ACER-801 (Osanetant) in Men with Adenocarcinoma of the Prostate (GlobeNewswire) - "Acer Therapeutics Inc...announced the initiation of two Phase 2, single-arm investigator-sponsored trials evaluating ACER-801 (osanetant) in men with adenocarcinoma of the prostate....The POSH-MAP trial will evaluate the ability of ACER-801 to reduce hot flash frequency and severity and improve quality of life measures in men with prostate cancer following 28 days of therapy....The second trial, PORT-MAP, will evaluate the ability of ACER-801 to suppress testosterone production in men with prostate cancer within 28 days prior to a planned prostatectomy."

Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

POSH-MAP: Pilot of Osanetant to Reduce Severity of Hot Flashes in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Kansas Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Prostate Cancer • Solid Tumor

POSH-MAP: Pilot of Osanetant to Reduce Severity of Hot Flashes in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: University of Kansas Medical Center

New P1 trial • Oncology • Prostate Cancer • Solid Tumor

PORT-MAP: Pilot of Osanetant to Reduce Testosterone in Men With Adenocarcinoma of the Prostate (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: University of Kansas Medical Center

New P1 trial • Oncology • Prostate Cancer • CAST

Acer Therapeutics Announces Expansion of ACER-801 (osanetant) Development Indications to Include Post-Traumatic Stress Disorder (GlobeNewswire) - "Acer Therapeutics...announced the expansion of ACER-801 (osanetant) into a new indication, for the reduction of the frequency and severity of acute stress disorder and post-traumatic stress disorder (PTSD)....Acer previously entered into an agreement with Emory for an exclusive world-wide license to US Patent No. 10,314,835, US Application 15/320,952, and European Patent No. EP3160469 covering certain methods of treating or preventing PTSD with osanetant."

Clinical • Patent • CNS Disorders • Post-traumatic Stress Disorder

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Recruiting | Sponsor: Acer Therapeutics Inc. | Enrolling by invitation ➔ Recruiting | Trial completion date: Sep 2022 ➔ Jan 2023 | Trial primary completion date: Aug 2022 ➔ Dec 2022

Enrollment status • Trial completion date • Trial primary completion date

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Enrolling by invitation | Sponsor: Acer Therapeutics Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Recruiting | Sponsor: Acer Therapeutics Inc. | Trial completion date: Dec 2022 ➔ Sep 2022

Trial completion date

Nk3R blockade has sex-divergent effects on memory in mice. (PubMed, Biol Sex Differ) - "These data propose novel ideas on functional interactions between Nk3R, sex hormones, estrogen receptors, and androgen receptors in memory consolidation."

Journal • Preclinical • AR • ER

Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause (clinicaltrials.gov) - P2a | N=56 | Recruiting | Sponsor: Acer Therapeutics Inc.

New P2a trial

The role of Angiotensin II in Fear Memory and therapeutic opportunities for PTSD (Neuroscience 2021) - "We will also show that Neurokinin 3 receptor (Nk3R) neuropeptide antagonist osanetant enhances memory consolidation in female mice whereas it impairs memory consolidation in males. Finally, we will present data from human subjects showing that highly selective vasopressin 1A receptor antagonist SRX246 reduces anxiety but not fear-potentiated startle in male and female participants. This mini-symposium will address sex-specific effects of limbic neuropeptides in both rodents and humans and the importance of sex-specific pharmacotherapies for PTSD."

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

Sex-opposite effects of the neurokinin 3 receptor neuropeptide in memory consolidation (Neuroscience 2021) - "We will also show that Neurokinin 3 receptor (Nk3R) neuropeptide antagonist osanetant enhances memory consolidation in female mice whereas it impairs memory consolidation in males. Finally, we will present data from human subjects showing that highly selective vasopressin 1A receptor antagonist SRX246 reduces anxiety but not fear-potentiated startle in male and female participants. This mini-symposium will address sex-specific effects of limbic neuropeptides in both rodents and humans and the importance of sex-specific pharmacotherapies for PTSD."

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

Clinical translation of oxytocin neuroscience to the treatment of anxiety and posttraumatic stress disorders (Neuroscience 2021) - "We will also show that Neurokinin 3 receptor (Nk3R) neuropeptide antagonist osanetant enhances memory consolidation in female mice whereas it impairs memory consolidation in males. Finally, we will present data from human subjects showing that highly selective vasopressin 1A receptor antagonist SRX246 reduces anxiety but not fear-potentiated startle in male and female participants. This mini-symposium will address sex-specific effects of limbic neuropeptides in both rodents and humans and the importance of sex-specific pharmacotherapies for PTSD."

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