Neuphoria’s Phase 3 AFFIRM-1 study of BNC210 for the acute treatment of social anxiety disorder failed to demonstrate efficacy. The trial did not meet its primary endpoint—change from baseline to the average of the performance phase of a public speaking challenge on the Subjective Units of Distress Scale—and none of the secondary endpoints, including SUDS during anticipation, CGI-S, STAI-State, or PGI-I, reached statistical significance. Safety and tolerability were consistent with prior studies.
The company is discontinuing development of BNC210 for social anxiety disorder and initiating a strategic review of operations and portfolio. Neuphoria will pause further investment across programs while it evaluates options, with a stated intent to consider next steps for BNC210 in post-traumatic stress disorder, where it has previously reported positive signals under chronic daily dosing. The company also pointed to its ongoing collaboration with Merck, which fully funds MK-1167, a positive allosteric modulator being tested in a Phase 2 Alzheimer’s disease study. Neuphoria reported $14.2 million in cash and cash equivalents as of June 30, 2025, and guided that its current resources, alongside cost controls, are expected to fund operations through the second fiscal quarter of 2027.
Strategically, this is a reset forced by the inherent fragility of acute anxiety challenge paradigms in late-stage development. AFFIRM-1 was a multicenter, double-blind, parallel-group, placebo-controlled trial testing a single 225 mg dose of BNC210 versus placebo, administered one hour before a standardized public speaking task. These designs are operationally sensitive—timing, site training, and patient conditioning can drive variability—and rely on subjective scales that are vulnerable to placebo response. In a market where rapid symptom relief is already met with generic options, a clean safety profile was unlikely to compensate for an absence of clear efficacy. The pivot away from acute SAD suggests Neuphoria is prioritizing paths with potentially steadier signal detection and regulatory narratives, namely chronic dosing in PTSD, while leaning on the Merck partnership to preserve optionality.
For stakeholders, the impact is immediate. Sites and CROs with capabilities in laboratory-based anxiety challenge models may see fewer late-phase SAD contracts as sponsors reassess the risk-reward of subjective endpoints for registration. A move toward chronic PTSD development would shift operational emphasis to longer outpatient trials, centralized raters, and durability measures, which affects staffing models and monitoring cadence. Sponsors should note the broader pattern: regulators and payers are pressing for clinically meaningful outcomes beyond lab stress tests, and late-stage programs that have not de-risked placebo response and endpoint consistency across diverse sites face elevated failure risk. Vendors developing objective physiologic or digital biomarkers of anxiety may find renewed interest as companies seek to mitigate subjectivity in measurement.
The near-term watchlist centers on three questions. First, the scope and outcome of Neuphoria’s strategic review by year-end—whether it results in asset out-licensing, headcount and burn reductions, or a broader corporate transaction. Second, clarity on the PTSD plan, including funding, study design, and whether prior chronic dosing data are robust enough to warrant a pivotal path. Third, the trajectory of the Merck-led MK-1167 program, which sits outside Neuphoria’s control but could deliver non-dilutive milestones if Phase 2 reads positive. Unresolved issues include whether AFFIRM-1’s miss reflects dose selection, dosing window, patient selection, or the limitations of the SUDS-based public speaking paradigm itself. The answer will shape whether BNC210 retains strategic value beyond SAD—and whether Neuphoria can credibly reposition around indications with a more forgiving operational and regulatory profile.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
