Small Molecule · BNC210

BNC210 (soclenicant)

Phase 2Neuphoria Therapeutics, Inc. (NEUP)
  • Fast Track

Oral, brain-penetrant, selective NEGATIVE allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (alpha7 nAChR / CHRNA7), a 1,8-naphthyridin-4(1H)-one (INN soclenicant; originally coded IW-2143). Developed by Bionomics (now Neuphoria Therapeutics) as a non-sedating, non-addictive anxiolytic for trauma- and stressor-related disorders. The Phase 2b ATTUNE study met its CAPS-5 primary endpoint in PTSD and FDA Fast Track was granted, but the dedicated Phase 3 PTSD trial was never initiated; after the company's separate Phase 3 in social anxiety disorder failed (Oct 2025), the PTSD program was paused amid a corporate restructuring and strategic review.

Also known as: BNC210, BNC-210, IW-2143, soclenicant, 1020634-41-6, 6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(morpholine-4-carbonyl)-1,8-naphthyridin-4(1H)-one

Data current as of

Modality
Small molecule
Chemical class
1,8-naphthyridin-4-one, morpholine
Chemistry
Achiral
Mechanism
alpha7 nAChR NAM
Highest phase
Phase 2
Lead indication
Post-traumatic stress disorder
Developer
Neuphoria Therapeutics, Inc. (NEUP)
Designations
Fast Track
Trials
2 tracked · 53 sites

Mechanism of action

Selective negative allosteric modulator (NAM) of the alpha-7 nicotinic acetylcholine receptor (alpha7 nAChR; CHRNA7), partially inhibiting alpha7 channel activation while sparing alpha4beta2 nAChR signalling. By dampening alpha7-mediated cholinergic tone in fear/stress circuitry it produces anxiolytic and PTSD-symptom-reducing effects without sedation or dependence. No quantitative binding/inhibitory constant for the NAM action is published in IUPHAR/GtoPdb or ChEMBL.

TargetActionAffinity
alpha7 nAChRprimaryCHRNA7NAM—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
BNC210 oral tablet (as-needed, SAD)spray-dried dispersion solid dose tablet
225 mg or 675 mg single as-needed dose (PREVAIL Phase 2, acute)
OralSingle doseTmax 2 h
BNC210 oral tablet (PTSD)spray-dried dispersion solid dose tablet
900 mg twice daily over 12 weeks (Phase 2b, NCT04951076)
OralTwice dailyTmax 2 h

Development timeline

Phase 2Sept 2023 – Oct 2025
  1. mixedPhase 3 PTSD trial (planned 2H 2025) never started; PTSD program paused after the SAD Phase 3 failure.Post-traumatic stress disorder↗
  2. metATTUNE full results published in NEJM Evidence; hepatic enzyme elevations flagged.Post-traumatic stress disorder↗
  3. Successful FDA End-of-Phase-2 meeting (held 26 Jun 2024): FDA supported a path to NDA for PTSD with a single Phase 3 trial (900 mg and 600 mg BID, 12-week double-blind + 52-week open-label extension, CAPS-5 primary). BNC210 holds FDA Fast Track designation for PTSD.Post-traumatic stress disorder↗
  4. metPhase 2b ATTUNE met its primary CAPS-5 endpoint in PTSD (p=0.048).Post-traumatic stress disorder↗
DiscontinuedOct 2025
  1. missedPhase 3 AFFIRM-1 missed its primary SUDS endpoint in social anxiety disorder; Neuphoria discontinues the SAD program.Social anxiety disorder↗
Phase 3Aug 2024 – Sept 2025
  1. AFFIRM-1 reaches primary completion (11 Sep 2025); 370 participants enrolled (actual). Trial record marked Completed on ClinicalTrials.gov.Social anxiety disorder
  2. Phase 3 AFFIRM-1 (NCT06510504) in social anxiety disorder begins (study start 6 Aug 2024). Randomized, double-blind, placebo-controlled, single acute as-needed dose of 225 mg BNC210 vs placebo evaluated in a public speaking challenge model; primary endpoint = change from baseline in average performance-phase SUDS. Lead sponsor Bionomics Limited (Neuphoria Therapeutics).Social anxiety disorder

BNC210 (soclenicant) for Post-traumatic stress disorder

Phase 2SuspendedPost-traumatic stress disorder indication →

Oral alpha7-nAChR NAM for PTSD. The Phase 2b ATTUNE study (NCT04951076; 900 mg BID vs placebo, 12 weeks, n=212 randomized / mITT 182) MET its primary CAPS-5 endpoint at Week 12 (LS mean difference -4.03, Cohen's d 0.40, p=0.048), with significant benefit on depression (MADRS, p=0.040) and sleep (ISI); results published in NEJM Evidence (Jan 2025, DOI 10.1056/EVIDoa2400380). BNC210 holds FDA Fast Track designation for PTSD, and a 26 Jun 2024 End-of-Phase-2 meeting endorsed a single confirmatory Phase 3 (900 mg and 600 mg BID, 12-week double-blind + 52-week open-label extension, CAPS-5 primary) as a path to NDA. However, that Phase 3 PTSD trial was never initiated: after the company's SEPARATE Phase 3 AFFIRM-1 trial in social anxiety disorder MISSED its primary and secondary endpoints (20 Oct 2025), Bionomics/Neuphoria discontinued the SAD program and PAUSED the BNC210 PTSD program, terminated nearly all employees, and entered a strategic review. PTSD development remains paused (not discontinued) as of mid-2026.

Readouts

  • 2H 2025CancelledRegulatorymixed

    Phase 3 PTSD trial (planned 2H 2025) never started; PTSD program paused after the SAD Phase 3 failure. ↗

  • 2024-12-09ReportedFull resultsmetNCT04951076

    ATTUNE full results published in NEJM Evidence; hepatic enzyme elevations flagged. ↗

  • 2023-09-29ReportedTopline datametNCT04951076

    Phase 2b ATTUNE met its primary CAPS-5 endpoint in PTSD (p=0.048). ↗

BNC210 (soclenicant) for Social anxiety disorder

DiscontinuedDiscontinuedSocial anxiety disorder indication →

Oral alpha7-nAChR negative allosteric modulator developed for the acute, as-needed treatment of anxiety in social anxiety disorder (SAD). The Phase 3 AFFIRM-1 trial (NCT06510504; n=370; single acute dose of 225 mg BNC210 vs placebo, 1:1) used a public speaking challenge model: subjects were dosed ~1 hour before being introduced to the challenge, given ~2 minutes to prepare (anticipation phase), then delivered a 5-minute speech before a small audience (performance phase). On 20 October 2025 Neuphoria announced AFFIRM-1 MISSED its primary endpoint - change from baseline to the average of the performance-phase Subjective Units of Distress Scale (SUDS) score during the public speaking challenge - and that analyses of secondary endpoints did not demonstrate statistically significant differences. BNC210 safety/tolerability remained favorable. Based on these results, Neuphoria DISCONTINUED further development of the SAD program and launched a full strategic review of its operations and portfolio; the company indicated it would separately evaluate next steps for BNC210 in PTSD (where chronic daily dosing had been positive). The SAD program is discontinued.

Readouts

  • 2025-10-20ReportedTopline datamissedNCT06510504

    Phase 3 AFFIRM-1 missed its primary SUDS endpoint in social anxiety disorder; Neuphoria discontinues the SAD program. ↗

Clinical trials

NCT06510504AFFIRM-1Phase 3Completedn=370

A Phase 3, Randomized, Double-blind, 2-arm, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of BNC210 for the Acute, As-needed Treatment of Anxiety in Adults With Social Anxiety Disorder (AFFIRM-1)

Started Aug 2024· Primary completion Sept 2025· 📍 21 sites across 1 country (United States)

missedprimaryChange from baseline in average performance-phase SUDS (Subjective Units of Distress Scale) during the public speaking challenge

AFFIRM-1 did not meet its primary endpoint: a single acute as-needed 225 mg dose of BNC210 did not significantly reduce the average performance-phase SUDS score during the public speaking challenge versus placebo. Topline announcement; quantitative effect size and p-value not disclosed in the company PR.

pendingsafetySafety / tolerability

The safety and tolerability profile of BNC210 continued to be favorable and was consistent with previously reported studies. No detailed adverse-event tabulation disclosed in the topline PR; outcome marked pending as full safety data have not been published.

missedsecondarySecondary efficacy endpoints (social anxiety / distress measures)

Analyses of secondary endpoints did not demonstrate statistically significant differences between BNC210 and placebo.

NCT04951076ATTUNEPhase 2Completedn=212

A Phase 2b, Randomized, Double Blind, Two Arm Study to Investigate the Effects of BNC210 Tablet Formulation Compared to Placebo in Adults With Post-Traumatic Stress Disorder (PTSD)

Started Jul 2021· Primary completion Jul 2023· 📍 32 sites across 2 countries (United States, United Kingdom)

metprimaryCAPS-5 total symptom severity, change from baseline to Week 12 — LS mean difference -4.03 (Cohen's d 0.40) (0.048)

BNC210 900 mg BID improved CAPS-5 vs placebo at Week 12 (mITT n=182), with separation as early as Week 4. Primary endpoint met.

metsecondaryMADRS depressive symptoms, change from baseline to Week 12 — LS mean difference -3.19 (0.040)

Statistically significant improvement in depressive symptoms (MADRS); meaningful improvement in sleep (ISI) also reported.

mixedsafetySafety / tolerability (treatment-emergent adverse events)

TEAEs in 66.7% (BNC210) vs 53.8% (placebo); most common headache, nausea, fatigue and hepatic enzyme elevations. 21 BNC210 vs 10 placebo discontinued for AEs; no serious AEs or deaths in the BNC210 group.

Related compounds

Other alpha7 nAChR compounds

  • VQW-765Phase 3Social anxiety disorder
  • MK-1167Phase 2Alzheimer's disease

Identifiers

Sources

  1. A phase 2, placebo-controlled study to evaluate the efficacy and safety of BNC210 for acute, as-needed treatment of social anxiety disorder (SAD) - The PREVAIL study — PubMed (Psychiatry Research)
  2. AFFIRM-1: Phase 3 study of BNC210 for acute as-needed treatment of anxiety in social anxiety disorder (NCT06510504) — ClinicalTrials.gov
  3. ATTUNE: Phase 2b study of BNC210 vs placebo in PTSD (NCT04951076) — ClinicalTrials.gov
  4. Bionomics announces positive topline results from the Phase 2b ATTUNE trial of BNC210 in PTSD — Bionomics Limited (PR Newswire)
  5. Bionomics announces successful End-of-Phase-2 meeting with the FDA on BNC210 in PTSD — Bionomics / Neuphoria Therapeutics (IR)
  6. Bionomics BNC210 Expansion into Social Anxiety Disorder — Bionomics / PR Newswire
  7. BNC210, an alpha7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder (ATTUNE) — NEJM Evidence 2025;4(1):EVIDoa2400380
  8. Neuphoria provides update on AFFIRM-1 Phase 3 (SAD missed); SAD discontinued, PTSD paused, strategic review — Neuphoria Therapeutics (IR)
  9. Neuphoria Therapeutics Provides Update on AFFIRM-1 Phase 3 Trial Evaluating BNC210 for the Acute Treatment of Social Anxiety Disorder — Neuphoria Therapeutics, Inc. (GlobeNewswire)
  10. Soclenicant / BNC210 (ligand 14250) - alpha7 nicotinic ACh receptor negative allosteric modulator — IUPHAR/BPS Guide to Pharmacology