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

The purpose of the study is to evaluate the effect of a single, acute dose of BNC210 compared to placebo on reducing the severity of anxiety provoked by a behavioral assessment task and measured using the Subjective Units of Distress Scale (SUDS) in adult patients with social anxiety disorder.

Start Date06 Aug 2024

Sponsor / Collaborator

Bionomics Ltd.

NCT05193409

/ CompletedPhase 2

A Phase 2, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of BNC210 Compared to Placebo for the Acute Treatment of Social Anxiety Disorder

The purpose of this study is to assess the effects of an acute dose of BNC210 compared to placebo on reducing anxiety provoked by a speaking challenge and measured using the Subjective Units of Distress Scale (SUDS) in patients with Social Anxiety Disorder (SAD).

Start Date02 Feb 2022

Sponsor / Collaborator

Bionomics Ltd.

NCT04951076

/ CompletedPhase 2

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)

The purpose of this study is to assess the effects of BNC210 compared to placebo on Post-Traumatic Stress Disorder (PTSD) symptom severity as measured by the Clinician Administered PTSD scale for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) Total Symptom Severity Scores.

Start Date27 Jul 2021

Sponsor / Collaborator

Bionomics Ltd.

100 Clinical Results associated with Sitmutolimod

100 Translational Medicine associated with Sitmutolimod

100 Patents (Medical) associated with Sitmutolimod

Literatures (Medical) associated with Sitmutolimod

01 Apr 2025·PSYCHIATRY RESEARCH

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

Article

Author: Paul, Dharam ; Doolin, Elizabeth ; Rolan, Paul ; Jaros, Mark ; Odontiadis, Michael ; Taylor, Charles ; Stein, Murray B ; Papapetropoulos, Spyros

Social anxiety disorder (SAD) is a chronic, debilitating, and prevalent neuropsychiatric condition for which an acute, as-needed therapy is an unmet medical need. This Phase 2 study evaluated a potential novel, fast-acting, anxiolytic, BNC210, in SAD patients (NCT05193409). PREVAIL was a placebo-controlled, acute dose study of 225 mg and 675 mg BNC210 in 151 adult participants with SAD. Anxiety was evaluated by self-report efficacy scales during the anticipation and performance phases of a simulated public speaking challenge. Safety data were collected. Least squares mean ± standard error (SE) differences compared to placebo for the Subjective Units of Distress Scale (SUDS) scores for the change from baseline to the average of the performance phase were -6.6 ± 4.75 for 225 mg BNC210 and -4.8 ± 4.73 for 675 mg BNC210 (not significant). A post hoc analysis of SUDS scores evaluating combined BNC210 doses and speaking challenge phases (anticipation and performance) revealed a nominally statistically significant reduction compared to placebo (p = 0.044; effect size 0.36). Both dose levels of BNC210 demonstrated a favorable safety profile. 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.

01 Jan 2025·NEJM evidence

BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder

Article

Author: Doolin, Elizabeth ; Paul, Dharam ; Rolan, Paul ; O’Connor, Susan ; Stein, Murray B. ; Papapetropoulos, Spyridon ; Jaros, Mark ; Odontiadis, Michael

BACKGROUND:

Post-traumatic stress disorder (PTSD) is a serious, debilitating, and prevalent psychiatric condition occurring in people who are traumatized and experience intense, disturbing thoughts and feelings that persist. BNC210 is a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator developed to treat PTSD.

METHODS:

ATTUNE was a randomized, double-blind, phase 2b, placebo-controlled trial. Patients between 18 and 75 years of age with a current PTSD diagnosis and a Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (CAPS-5) total symptom severity score of 30 or more were eligible (range: 0 to 80; in all scales used in this trial a higher score indicates a more severe condition). We randomly assigned patients 1:1 to a BNC210 dose of 900 mg twice daily or placebo for 12 weeks. The primary end point was a change from baseline to week 12 in CAPS-5 total score for BNC210 versus placebo.

RESULTS:

In the modified intent-to-treat population (n=182), an improvement in the CAPS-5 total score was observed with BNC210 compared with placebo (least squares [LS] mean difference: -4.03; Cohen's d effect size: 0.40; P=0.048) at week 12. A LS mean difference in CAPS-5 score of -4.11 was observed as early as week 4. The LS mean difference to week 12 for depressive symptoms measured on the Montgomery-Åsberg Depression Rating Scale (range: 0 to 60; minimal clinically important difference [MCID] ≥2]) was -3.19 and for sleep measured on the Insomnia Severity Index (range: 0 to 28; MCID 6) was -2.19. Treatment-emergent adverse events (AEs) occurred in 70 (66.7%) patients in the BNC210 group and 56 (53.8%) in the placebo group, most commonly headache, nausea, fatigue, and hepatic enzyme elevations. In the BNC210 treatment group, 21 patients withdrew from treatment for AEs, while 10 did so in the placebo group. There were no serious AEs or deaths reported for the BNC210 group.

CONCLUSIONS:

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.).

01 Mar 2024·Neuropharmacology

BNC210, a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor, demonstrates anxiolytic- and antidepressant-like effects in rodents

Article

Author: Baell, Jonathan B ; Street, Ian P ; Sleebs, Brad E ; Paul, Dharam ; Andriambeloson, Emile ; Huyard, Bertrand ; Quazi, Nurul ; Coles, Carolyn ; Wagner, Stephanie ; Poiraud, Etienne ; de Souza, Errol B ; Flynn, Bernard L ; O'Connor, Susan M

This work describes the characterization of BNC210 (6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(4-morpholinylcarbonyl)-1,8-naphthyridin-4(1H)-one), a selective, small molecule, negative allosteric modulator (NAM) of α7 nicotinic acetylcholine receptors (α7 nAChR). With the aim to discover a non-sedating, anxiolytic compound, BNC210 was identified during phenotypic screening of a focused medicinal chemistry library using the mouse Light Dark (LD) box to evaluate anxiolytic-like activity and the mouse Open Field (OF) (dark) test to detect sedative and/or motor effects. BNC210 exhibited anxiolytic-like activity with no measurable sedative or motor effects. Electrophysiology showed that BNC210 did not induce α7 nAChR currents by itself but inhibited EC₈₀ agonist-evoked currents in recombinant GH4C1 cell lines stably expressing the rat or human α7 nAChR. BNC210 was not active when tested on cell lines expressing other members of the cys-loop ligand-gated ion channel family. Screening over 400 other targets did not reveal any activity for BNC210 confirming its selectivity for α7 nAChR. Oral administration of BNC210 to male mice and rats in several tests of behavior related to anxiety- and stress- related disorders, demonstrated significant reduction of these behaviors over a broad therapeutic range up to 500 times the minimum effective dose. 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.

News (Medical) associated with Sitmutolimod

28 Oct 2025

·endpoints.news

Regeneron discloses CRL; AbbVie stops work on Dragonfly asset

Plus, news about Cybin, Incyte, Roche, Merck, Eisai, Neuphoria Therapeutics, Aldeyra Therapeutics and X4 Pharmaceuticals: 🏭 FDA issues CRL to Regeneron: The drugmaker has officially been handed a complete response letter for its pre-filled syringe for Eylea HD. The company had warned in August that it expected regulatory delays after issues were found at a Catalent site in Bloomington, IN, that’s now owned by Novo Nordisk. The plant has since been issued an “official action indicated” classification. Another customer of the Indiana site, Scholar Rock, also received a CRL related to the plant. — Anna Brown 🧪 AbbVie scraps asset licensed from Dragonfly Therapeutics: The Chicago-area pharma giant terminated a Phase 1 test of the first asset that it licensed from Dragonfly . AbbVie started testing ABBV-303/DF4101 in 2024 in solid tumors. Dragonfly CEO Bill Haney told Endpoints News that the company’s other programs with AbbVie are ongoing. Dragonfly has multiple internal candidates in clinical testing as well as Phase 1 programs with Bristol Myers Squibb and Merck. It also has a preclinical pact with Gilead. — Kyle LaHucik 💵 Cybin’s $175M direct offering: The company is selling about 22.3 million shares at $6.51 apiece from several blue-chip investors, including Venrock Healthcare Capital Partners, OrbiMed and Point72. It’s developing a psychedelic called CYB003 as a treatment for major depressive disorder. — Jaimy Lee 🛠️ Incyte halts work on two drugs: Under new CEO Bill Meury, the drugmaker has paused development of its anti-CD122 candidate, called INCA034460, and its BET inhibitor, called INCB57643. The biotech also ended povorcitinib’s development in chronic spontaneous urticaria and hinted that more pipeline adjustments are in the works. “We are taking a deliberate approach to pipeline prioritization. We are actively reviewing our R&D efforts and focusing on high-value programs that are scientifically differentiated, address unmet medical needs, and have the potential to significantly drive Incyte’s next phase of growth,” Meury said in a release. Incyte also raised its revenue guidance for the year. It’s now in the range of $4.23 billion to $4.32 billion. — Kyle LaHucik 🔬 Roche’s Gazyva succeeds in kidney disorder: The drug met its primary endpoint in a Phase 3 study for idiopathic nephrotic syndrome, a rare autoimmune disease that affects the kidneys. Roche will head to the FDA to discuss next steps for the drug, but the timing is not yet clear. Gazyva was approved earlier this month for the treatment of active lupus nephritis. — Max Gelman 💊 Merck, Eisai tout kidney cancer data: The combination of Merck’s Welireg and Eisai’s Lenvima achieved a statistically significant improvement in progression-free survival over Exelixis’ Cabometyx in advanced renal cell carcinoma. Overall survival did not reach statistical significance, though Merck and Eisai noted this was an interim analysis. There was also a “trend toward improvement” on OS. — Max Gelman 📈 Neuphoria Therapeutics adopts poison pill after Phase 3 fail: The biotech’s board selected the shareholder rights plan to “protect the interest of the company and its stockholders.” The move lowers the chances that a person or group will accumulate enough shares to control Neuphoria. The biotech’s social anxiety drug failed a Phase 3 trial last week, and the company decided to drop the asset, named BNC210. The biotech’s stock price $NEUP was up almost 6% in premarket trading on Tuesday. — Kyle LaHucik 💼 Aldeyra Therapeutics updates its pipeline: The biotech discontinued work on ADX-629 in patients with Sjögren-Larsson Syndrome. It also said it expects to file INDs for a pair of RASP modulators sometime next year. — Jaimy Lee 💰 X4 Pharmaceuticals ended up raising $155.3 million in its public offering, up from the $135 million it set out to raise. — Jaimy Lee

Phase 3Clinical ResultPhase 1Drug Approval

21 Oct 2025

·www.fiercebiotech.com

Neuphoria nixes social anxiety program and starts strategic review after phase 3 flop

Neuphoria Therapeutics’ stock has plummeted 67%, dropping from Monday’s close of $15.40 per share to $5 as of 10 a.m. ET today.\n Neuphoria Therapeutics’ lead candidate has failed to improve social anxiety symptoms in a late-stage trial, prompting the biotech to discontinue the program and launch a strategic review of its business.The program in question is Neuphoria’s BNC210, also known as soclenicant, an α7 nicotinic receptor negative alteration modulator. A single 225-mg dose of BNC210 was tested against placebo in a double-blind phase 3 trial for acute treatment of social anxiety disorder.The program failed to hit the study’s primary endpoint, which measured change from baseline on an industry “distress scale” during a public speaking challenge, according to an Oct. 20 release shared after market close.The trial, dubbed Affirm-1, also failed to demonstrate statistically significant changes on secondary endpoints, which included self-assessments and clinician-measured assessments.The safety and tolerability of the drug remained favorable, according to Neuphoria. The company has touted the candidate as providing rapid stress relief without common side effects that can be associated with currently approved treatments, like sedation or cognitive impairment.Neuphoria’s stock has plummeted 67% after the announcement, dropping from Monday’s close of $15.40 per share to $5 as of 10 a.m. ET today.Now, the Massachusetts-based biotech is discontinuing further development of BNC210 in social anxiety disorder. “We plan to immediately take action to conserve our cash position by holding further investment in our programs and evaluating all options for Neuphoria’s path forward through a strategic review, with the goal of maximizing value for shareholders,” Neuphoria CEO Spyros Papapetropoulos, M.D., Ph.D., said in the release.The biotech plans to assess next steps for BNC210 in post-traumatic stress disorder (PTSD), citing “previous positive data with chronic daily dosing.” At the end of September, Neuphoria said it was ramping up activities for a phase 2b/3 trial in PTSD that was expected to launch in the first half of 2026. Neuphoria said it would provide an update from the strategic review by the end of this year. As of June 30, the biotech had $14.2 million in cash and cash equivalents, money expected to fuel the company through the second fiscal quarter of 2027.Neuphoria also has an active partnership with Big Pharma Merck & Co. The pair is advancing two positive allosteric modulator candidates, one of which is currently being tested out in a Merck-led phase 2 study for Alzheimer’s disease. Merck is fronting the costs of the program, with Neuphoria in line to receive up to $450 million potential biobucks.The biotech also has a deal with Carina Biotech to develop a legacy oncology program.

Phase 2Phase 3Clinical Trial Failure

21 Oct 2025

·endpoints.news

Neuphoria scraps social anxiety drug; Minerva doubles down on schizophrenia therapy

Plus, news about Syncona, Ventus Therapeutics, Roche, Disc Medicine, Atai Life Sciences, Lexeo Therapeutics, Novartis, Vivace Therapeutics, Kura Oncology, Corbus and J&J: 💼 Neuphoria Therapeutics’ social anxiety drug fails Phase 3: The biotech is discontinuing BNC210 after the drug did not meet the primary endpoint in a public speaking challenge in the AFFIRM-1 trial. Neuphoria is now conducting a strategic review of its business and assessing what to do with BNC210 in post-traumatic stress disorder. It’s still partnered with Merck on a Phase 2 trial in Alzheimer’s disease. The company’s shares $NEUP were down about 68% the morning after it disclosed the results. — Jaimy Lee 🧠 Minerva Neurosciences’ up to $200M PIPE: The company gets $80 million upfront as it advances its experimental schizophrenia treatment through a confirmatory Phase 3 trial. It then plans to resubmit roluperidone to the FDA. Vivo Capital led the financing. The FDA has twice declined to approve the drug. Its stock price $NERV soared 275% on Tuesday morning after disclosing the private placement. — Jaimy Lee 📋 Syncona details plans to recoup £250M for shareholders: Earlier this year, the British life sciences investment firm announced it won’t hit its 2032 goals of £5 billion in assets, launching three companies each year, and having a portfolio of at least 20 startups. It may sell mature portfolio companies, update the board or establish a new private fund. The firm still plans to invest in early-stage companies. “We are committed to ensuring shareholders benefit from the potential returns available as markets stabilize,” Syncona Investment Management CEO Chris Hollowood said in a statement. — Jaimy Lee 🧪 Ventus Therapeutics, Roche ink licensing deal: Roche’s Genentech could pay more than $460 million plus royalties to use Ventus’ AI and machine learning platform to develop small molecules. The companies didn’t disclose the targets, though they described them as “challenging” and in “major disease areas.” — Jaimy Lee 💰 Disc Medicine raised a total of $250 million in its stock sale, above the $220 million it set out to raise. Atai Life Sciences also had an upsized offering, selling $149.5 million in shares. It had intended to sell about $130 million . The same goes for Lexeo Therapeutics , which raised $153.8 million , up from its plans to sell $135 million in shares. — Jaimy Lee ↔️ #ESMO25: One step back, one step forward for a rare cancer: Novartis told Endpoints News it is ending enrollment in a Phase 1 trial of IAG933 in advanced mesothelioma and other solid tumors, citing “tolerability and anti-tumor activity.” Meanwhile, Vivace Therapeutics reported promising Phase 1/2 results for its candidate, VT3989, in refractory mesothelioma. The drug achieved a 32% overall response rate and disease control rate of 86%. — Ayisha Sharma 🔬 #ESMO25: Kura Oncology details new vision for an old drug class: The company reported that its farnesyl transferase inhibitor darlifarnib combined with Exelixis’ Cabometyx, resulted in response rates of 33% to 50% across doses in kidney cancer patients. That included patients who previously progressed on Cabometyx. Kura’s vision is to use darlifarnib in combination with other targeted drugs as a way to overcome resistance that eventually develops to the treatments. — Lei Lei Wu 💊 #ESMO25: Corbus, Johnson & Johnson’s showdown in head and neck cancer: Corbus drew eyes with Phase 1/2 data for its nectin-4 targeting antibody-drug conjugate, which is called CRB-701. The drug achieved response rates ranging from about 33% to 48% in head and neck squamous cell carcinoma, depending on the dose. J&J is also eyeing HNSCC with Rybrevant. The bispecific antibody produced an overall response rate of 45% in a cohort of Phase 1b/2 patients with HPV-unrelated recurrent or metastatic disease, according to the presentation. — Ayisha Sharma

Phase 3Phase 1Phase 2Clinical Result

100 Deals associated with Sitmutolimod

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Indication	Highest Phase	Country/Location	Organization	Date
Anxiety Disorders	Phase 3	United States	Bionomics Ltd.	06 Aug 2024
Phobia, Social	Phase 3	United States	Bionomics Ltd.	06 Aug 2024
Agitation	Phase 2	Australia	Bionomics Ltd.	17 May 2018
Stress Disorders, Post-Traumatic	Phase 2	United States	Bionomics Ltd.	30 Jun 2016
Stress Disorders, Post-Traumatic	Phase 2	Australia	Bionomics Ltd.	30 Jun 2016
Depressive Disorder	Phase 1	-	Ironwood Pharmaceuticals, Inc.	-
Seasonal Affective Disorder	Preclinical	Australia	Bionomics Ltd.	22 Jan 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06510504 (Affirm-1, FierceBiotech) Manual	Phase 3	Phobia, Social	-	BNC210	sjlftuawmu(xlgoqzvmtt) = failed to hit loajhjzcgv (govklibnch ) Not Met View more	Negative	21 Oct 2025
				Placebo
NCT05193409 (PREVAIL, CTgov)	Phase 2	Phobia, Social	151	225 mg BNC210 (225 mg BNC210)	gtmkazthiu(omsxupjcbr) = kloujaobpe lorcirzfks (gfgyqilkbi, wfcyzmpcvh - jluerltvif) View more	-	18 Mar 2025
				675 mg BNC210 (675 mg BNC210)	gtmkazthiu(omsxupjcbr) = rueoaappni lorcirzfks (gfgyqilkbi, kigwxtuhrb - ibvcfwwipn) View more
NCT04951076 (ATTUNE, CTgov)	Phase 2	Stress Disorders, Post-Traumatic	212	Placebo	blbyiyfkeu(sngreltggz) = rhjukvkgdl wgnkerxjfb (uiytwyxbjy, 1.469) View more	-	06 Feb 2025
NCT04951076 (ATTUNE, NEJM Evid) Manual	Phase 2	Stress Disorders, Post-Traumatic	182	BNC210 900 mg twice daily	fiocjjyyol(zmqstqygwk): Difference (LS Mean) = 4.03, P-Value = 0.048 View more	Positive	08 Dec 2024
				placebo
NCT05193409 (PREVAIL, GlobeNewswire) Manual	Phase 2	Phobia, Social	-	BNC210	qllgjyxokm(rforueshku) = BNC210 225 mg and 675 mg demonstrated reduced anxiety in patients with moderate to severe SAD in a public speaking challenge compared to placebo. woffeqmrjq (dengfqqiga )	Positive	06 Dec 2023
				Placebo
NCT02933606 (RESTORE, CTgov)	Phase 2	Stress Disorders, Post-Traumatic	193	BNC210 (BNC210 600 mg b.i.d.)	wxafletbqx(ggtaaftakp) = bcmuryefns headbyxubn (rehssogxgt, nvodnvyxsi - vipwzzztud) View more	-	27 Feb 2023
				BNC210 (BNC210 300 mg b.i.d.)	wxafletbqx(ggtaaftakp) = kdkogdbgah headbyxubn (rehssogxgt, xumklddbxu - vdqrfpavuu) View more

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