Bionomics Limited announced the release of the full dataset analysis from its Phase 2b ATTUNE trial in patients with post-traumatic stress disorder. In September 2023, Bionomics reported the topline results for the Phase 2b ATTUNE trial of BNC210 in patients with PTSD demonstrating that the trial met its primary endpoint and several secondary endpoints, and that BNC210 was generally well tolerated. ATTUNE Phase 2b Trial Efficacy Results: ATTUNE achieved its primary and several secondary endpoints highlighting the potential of BNC210 to address multiple key symptoms experienced by patients with PTSD.

Effects were observed as early as Week 4 supporting potential for rapid onset of clinical efficacy compatible with BNC210?s mechanism of action. The primary endpoint of mean change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity score was met showing that BNC210 led to a statistically significant improvement vs placebo (p<0.05) at Week 12 with an effect size of 0.40. The improvement in CAPS-5 score was observed as early as Week 4 (p<0.05, effect size 0.40) and continued through Week 8 (p<0.05, effect size 0.44) till the end of the treatment period, supporting a rapid onset and clinically meaningful and sustained effect of BNC210.

Within the CAPS-5 symptom clusters, statistically significant results at Weeks 4, 8 and 12 were achieved for intrusion symptoms, which is a crucial aspect of successful management of PTSD symptoms (Criterion B, p<0.05). Additionally, statistically significant results were achieved for negative alterations in cognitions and mood at Week 4 and Week 8 (Criterion D, p<0.05). Treatment with BNC210 led to statistically significant improvement (p<0.05) in the following secondary endpoints: depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at Week 12, and sleep as measured by the Insomnia Severity Index (ISI) at Weeks 4, 8 and 12.

BNC210 treatment showed improvement trends (p<0.1) across visits in the other secondary endpoints including the clinical and patient global impressions severity scales (CGI-S, PGI-S), the Hamilton Anxiety Rating scale (HAM-A), and the Sheehan Disability Scale (SDS). ATTUNE Phase 2b Trial Safety Results: Overall, BNC210 continued to demonstrate a favorable safety profile for a psychoactive experimental therapeutic. 66.7% of patients in the BNC210 arm and 53.8% of patients in the placebo arm reported at least one treatment-emergent adverse event (AEs).

Most AEs were mild or moderate. No serious AEs were reported with BNC210. The most common (>5% of subjects in each group) reported AEs were headache, nausea, fatigue, and hepatic enzyme (ALT, AST) increases.

There were no reports in excess of placebo in sexual side effects (e.g., decreased libido, erectile dysfunction) that are commonly associated with SSRI treatment. The most frequent reasons for discontinuations were AEs (14.6%), withdraw of consent (9.9%) and lost to follow-up (10.4%). Overall, there were more discontinuations from AEs in the BNC210 group (19.8%) vs placebo (9.4%).

Five patients in the BNC210 group (4.8%) and two patients in the placebo group (1.9%) discontinued treatment due to an increase in hepatic enzymes. These increases were not associated with liver injury or decompensation nor were there any elevations in bilirubin levels. There were no other system organ category (SOC) AE clusters or laboratory findings of note.

Upon trial completion, there were no withdrawal symptoms reported, including no rebound anxiety that is common with treatment cessation of SSRIs and benzodiazepines. Following the ATTUNE Phase 2b trial readout and based on a safety database of ~600 patients, BNC210 continues to demonstrate a non-sedating, non-habit forming, non-cognition impairing psychoactive profile. ATTUNE Phase 2b Trial Pharmacokinetics Analyses: BNC210?s novel and proprietary solid tablet formulation (900 mg twice daily) delivered a predictable pharmacokinetic (PK) profile exceeding the projected therapeutic exposures for PTSD by ~2x based on a pharmacometrics model that was developed using data from completed studies prior to the initiation of the ATTUNE Phase 2b trial.

The population PK and safety analyses revealed that the hepatic enzyme increases may be attributed to the high exposures achieved with 900 mg twice daily dose. In addition to the 900 mg twice daily dose, a lower BNC210 dose that may alleviate hepatic enzyme elevations will be tested in a subsequent late-stage clinical trial. Based on these efficacy and safety observations, the Company plans to discuss the Phase 2b ATTUNE results with the FDA in the second quarter this year and proceed to a late-stage trial in the fourth quarter of 2024.

The full results of the Phase 2b ATTUNE trial together with prior datasets from other Phase 1b and Phase 2 clinical studies in social anxiety disorder, generalized anxiety disorder and panic attacks support BNC210?s favorable efficacy, safety, and tolerability profile, especially over SSRIs, benzodiazepines and other available treatments for these disorders.