BNC210 / Bionomics - LARVOL DELTA

AFFIRM-1: Efficacy of BNC210 in Acute, As-needed Treatment of Anxiety in Social Anxiety Disorder - 1 (clinicaltrials.gov) - P3 | N=370 | Completed | Sponsor: Bionomics Limited | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Mood Disorders • Psychiatry • Social Anxiety Disorder

The Pathway to Proof-of-Concept for BNC210, a Negative Allosteric Modulator of the Alpha-7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric Disease. (PubMed, Clin Pharmacol Drug Dev) - "Collectively, the Phase 1 data demonstrated desired properties of BNC210 supporting proof-of-concept clinical trials. BNC210 is currently being developed for acute, as-needed treatment of social anxiety disorder and chronic treatment of post-traumatic stress disorder."

Journal • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Social Anxiety Disorder

AFFIRM-1: Efficacy of BNC210 in Acute, As-needed Treatment of Anxiety in Social Anxiety Disorder - 1 (clinicaltrials.gov) - P3 | N=332 | Active, not recruiting | Sponsor: Bionomics Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Mood Disorders • Psychiatry • Social Anxiety Disorder

Neuphoria Therapeutics Inc…announced the achievement of target enrollment of 332 participants in the AFFIRM-1 Phase 3 trial evaluating lead candidate BNC-210…for social anxiety disorder (SAD). (The Manila Times) - "Achieving this milestone puts us on a clear path toward our first Phase 3 data for BNC-210, now expected early in the fourth quarter."

Enrollment status • P3 data • Social Anxiety Disorder

Neuphoria Provides a Review of 2024 and Highlights 2025 Plans (GlobeNewswire) - "Initiated the Phase 3 AFFIRM-1 trial with 225mg BNC210...The Phase 3 AFFIRM-1 trial is progressing as planned with enrollment being on-track for topline results anticipated in Q3 2025....The Phase 2b study in PTSD is scheduled to begin in Q4 2025..."

New P2b trial • P3 data • Post-traumatic Stress Disorder

A phase 2, placebo-controlled study to evaluate the efficacy and safety of BNC210, an alpha-7 nicotinic receptor negative allosteric modulator, for acute, as-needed treatment of social anxiety disorder (SAD) - The PREVAIL study. (PubMed, Psychiatry Res) - P2 | "PREVAIL supported further testing of 225 mg BNC210 as a potential safe and effective anxiolytic for acute, as-needed treatment of SAD. A Phase 3 trial is ongoing."

Journal • P2 data • CNS Disorders • Mood Disorders • Psychiatry • Social Anxiety Disorder

ATTUNE: A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=212 | Completed | Sponsor: Bionomics Limited | Phase classification: P2b ➔ P2

Phase classification • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder. (PubMed, NEJM Evid) - P2b | "BNC210 improved PTSD symptom severity at week 12 with indications of effect as early as week 4. Our trial establishes equipoise for additional larger trials that are needed to determine the clinical utility of BNC210 for the treatment of PTSD. (Funded by Bionomics Limited; ClinicalTrials.gov number, NCT04951076.)."

Clinical • Journal • CNS Disorders • Depression • Fatigue • Insomnia • Mental Retardation • Mood Disorders • Pain • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder

Bionomics Announces Successful End-of-Phase 2 Meeting with the FDA on the Development of BNC210 in Post-Traumatic Stress Disorder (GlobeNewswire) - "Bionomics Limited...today announced the favorable outcomes of an EoP2 meeting with the FDA, supporting the advancement of its lead asset BNC210 for the treatment of PTSD into Phase 3 based on the positive results of the recently completed Phase 2b ATTUNE study....'Followings the recent initiation of the Phase 3 trial of BNC210 in social anxiety disorder (AFFIRM-1), we look forward to starting a Phase 3 trial in PTSD by the end of 2024'....The Company plans to submit the full Phase 3 protocol for FDA review prior to trial initiation. The company is finalizing the full study protocol and anticipates beginning the Phase 3 program in PTSD in Q4 2024."

Clinical protocol • FDA event • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Social Anxiety Disorder

AFFIRM-1: Efficacy of BNC210 in Acute, As-needed Treatment of Anxiety in Social Anxiety Disorder - 1 (clinicaltrials.gov) - P3 | N=332 | Recruiting | Sponsor: Bionomics Limited

New P3 trial • CNS Disorders • Mood Disorders • Psychiatry • Social Anxiety Disorder

A Phase 3, Double-Blind, Placebo-Controlled Study for BNC210, an Alpha7 Nicotinic Receptor Negative Allosteric Modulator, for the Acute Treatment of Anxiety in Social Anxiety Disorder (AFFIRM-1) (ASCP 2024) - "Describe BNC210 mechanism of action and profile 2. Describe the design of AFFIRM-1, a Ph3 randomized placebo control study"

Clinical • P3 data • CNS Disorders • General Anxiety Disorder • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Social Anxiety Disorder

Positive Results Achieved in a Phase 2b, Double-Blind, Placebo-Controlled Study for BNC210, an Alpha7 Nicotinic Receptor Negative Allosteric Modulator, for the Treatment of PTSD (ATTUNE). (ASCP 2024) - "The most commonly reported treatment-emergent adverse events (>5% of subjects) were headache, nausea, and fatigue in the BNC210 and placebo treatment groups and asymptomatic hepatic enzyme increases in the BNC210 treatment group. In conclusion, positive results achieved in the ATTUNE Study support BNC210's potential as a safe and effective treatment for PTSD that will be further tested in future late-stage clinical trials."

Clinical • P2b data • CNS Disorders • Depression • General Anxiety Disorder • Insomnia • Mental Retardation • Pain • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder • Social Anxiety Disorder

Positive Results Achieved in a Phase 2b, Double-Blind, Placebo-Controlled Study for BNC210, an Alpha7 Nicotinic Receptor Negative Allosteric Modulator, for the Treatment of PTSD (ATTUNE). (ASCP 2024) - "Describe BNC210s' mechanism of action 2. Describe the results of the Ph2b ATTUNE clinical trial"

Clinical • P2b data • CNS Disorders • Depression • General Anxiety Disorder • Insomnia • Mental Retardation • Pain • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder • Social Anxiety Disorder

A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder. (PubMed, Drugs) - "Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders."

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

BNC210, a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor, demonstrates anxiolytic- and antidepressant-like effects in rodents. (PubMed, Neuropharmacology) - "Further testing for potential adverse effects in suitable rat and mouse tests showed that BNC210 did not produce sedation, memory and motor impairment or physical dependence, symptoms associated with current anxiolytic therapeutics. These data suggest that allosteric inhibition of α7 nAChR function may represent a differentiated approach to treating anxiety and stress-related disorders with an improved safety profile compared to current treatments."

Journal • Preclinical • Anesthesia • CNS Disorders • Depression • Mood Disorders • Psychiatry

Bionomics Completes Last Patient Last Visit in the Phase 2b ATTUNE Study for Post-Traumatic Stress Disorder (PTSD) and Confirms Expected 2023 Milestones with its Lead Asset BNC210 (GlobeNewswire) - "Bionomics Limited...announced that the last patient last visit has been completed in its Phase 2 ATTUNE study in PTSD, and disclosed timing of the End of Phase 2 (EoPh2) meeting to review advancing BNC210 into Phase 3 program in patients with SAD....Approximately 200 participants have been enrolled at 27 sites in the United States and 7 sites in the United Kingdom, and topline results are anticipated by the end of September 2023....The EoPh2 meeting to discuss advancing BNC210 into Phase 3 development as an acute treatment for SAD has been scheduled for mid-September 2023....The Company believes that the results from Phase 2 PREVAIL study support the progression of BNC210 into Phase 3 and plans to provide an update by the end of 2023 following the receipt of formal meeting minutes from the FDA. Additionally, Bionomics is scheduled to delist from the Official List of the Australian Securities Exchange on 28 August 2023."

FDA event • New P3 trial • P2 data • Trial status • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

ATTUNE: A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2b | N=212 | Completed | Sponsor: Bionomics Limited | Active, not recruiting ➔ Completed

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

A Phase 2, Double-Blind, Placebo-Controlled Study for BNC210, an Alpha7 Nicotinic Receptor Negative Allosteric Modulator (NAM) for the Acute Treatment of Social Anxiety Disorder (PREVAIL): Top-Line Efficacy and Safety Results (ASCP 2023) - "In completed clinical trials, acute treatment with BNC210 has reduced panic symptoms in a CCK-4 challenge in HVs and demonstrated inhibition of the amygdalar activity at resting, inhibition of anxiety-relevant neural circuits during the Emotional Faces task, and reduced threat avoidance behavior in patients with generalized anxiety disorder; and with at least equivalent if not better, responses than lorazepam when compared to placebo. Learning Objectives What is the mechanism of action of BNC210 in the treatment of social anxiety disorder? What are the top-line results of PREVAIL, a randomized, double-blind, placebo-controlled, 3-arm, parallel-group, multi-center Ph2 study?"

Clinical • Late-breaking abstract • P2 data • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder • Suicidal Ideation

ATTUNE: A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2b | N=200 | Active, not recruiting | Sponsor: Bionomics Limited | Recruiting ➔ Active, not recruiting | Trial completion date: May 2023 ➔ Aug 2023

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

Bionomics Announces the Completion of Enrollment in Phase 2b ATTUNE Clinical Trial of BNC210 in Patients with Post-Traumatic Stress Disorder (PTSD) (GlobeNewswire) - "Bionomics Limited...announced that the Company has completed target enrollment of approximately 200 participants in its randomized, double-blind, placebo-controlled, multi-center Phase 2b ATTUNE clinical trial evaluating BNC210 in Post-Traumatic Stress Disorder (PTSD). Topline results are expected in the third quarter of 2023."

P2b data • CNS Disorders • Post-traumatic Stress Disorder

BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders. (PubMed, Expert Opin Investig Drugs) - ": There is a relative paucity of data regarding BNC210, albeit the small amount of mostly non-peer reviewed data indicate it is a well-tolerated, effective anxiolytic. Phase III trials are required for proper appraisal of its utility."

Journal • Anesthesia • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Social Anxiety Disorder

PREVAIL: A Phase 2 Study of BNC210 for the Acute Treatment of Social Anxiety Disorder (clinicaltrials.gov) - P2 | N=151 | Completed | Sponsor: Bionomics Limited | Recruiting ➔ Completed

Trial completion • CNS Disorders • Mood Disorders • Psychiatry • Social Anxiety Disorder

Development of an Improved Oral Tablet Formulation of BNC210, a Negative Allosteric Modulator of the Alpha 7 Nicotinic Acetylcholine Receptor, Suitable for Evaluation as an Acute Treatment for Social Anxiety Disorder (ACNP 2022) - P2 | "The only FDA-approved drugs for SAD are select antidepressants (fluvoxamine, sertraline, paroxetine, venlafaxine) which are not suitable for acute treatment due to their slow (2-4 weeks) onset of action. BNC210 has been reformulated into a tablet with improved PK properties, potentially making it suitable for PRN use in an outpatient setting for the treatment of SAD. Drug exposure is no longer dependent on concomitant food intake, allowing for maximal plasma concentrations to be reached after approximately 1 to 1.5 hours after dose administration. This means that BNC210 could be taken just prior to an anticipated anxiety-provoking event such as a performance or social event."

CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder

Pharmacometrics Analysis and Drug Reformulation of BNC210 to Optimize Its Evaluation in a Phase 2 Trial in PTSD Patients (ACNP 2022) - P2, P2b | "The population PK model showed that exposure from the BNC210 liquid suspension formulation was insufficient to achieve efficacy in the RESTORE PTSD study where estimated mean AUC at steady state for the 600 mg b.i.d dose group was only 10,900 ng.hr/mL at Week 12. However, the pharmacometrics model predicted the potential for BNC210 to have benefit in PTSD provided that adequate blood levels could be achieved. These analyses, as well as the development of the new tablet formulation, justified further evaluation of BNC210 in PTSD patients and provided a basis for optimal design of the ongoing Phase 2b trial to demonstrate efficacy in PTSD (ATTUNE Study, NCT04951076); top line data are expected in mid-2023."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Suicidal Ideation

Bionomics to Host KOL Webinar on BNC210 and Social Anxiety Disorder (GlobeNewswire) - "Bionomics Limited...announced that it will host a Key Opinion Leader (KOL) webinar on BNC210, a proprietary, first-in-class oral therapeutic with potential to treat Social Anxiety Disorder (SAD) on Wednesday, October 12, 2022 at 2:30pm – 3:30pm ET....Bionomics’ Executive Chairman Errol B De Souza, PhD will provide an overview of their lead drug candidate, BNC210, an oral, proprietary, selective negative allosteric modulator of the α7 nicotinic acetylcholine receptor which has received Fast Track designation from the FDA for the acute treatment of SAD and other anxiety disorders....BNC210 also exhibits the potential to serve as a treatment for Post-Traumatic Stress Disorder (PTSD) which is being evaluated in an ongoing Phase 2b ATTUNE Study and for which it has been granted Fast Track designation."

Fast track designation • Review • CNS Disorders • Post-traumatic Stress Disorder • Social Anxiety Disorder