The Psychiatric Pipeline in Review: Quarter 2, 2025

The second quarter of 2025 saw some huge successes and fails in the psychiatric treatment pipeline. Here, learn more about what percentage of that news was positive vs negative, what disease states were most prominently featured, and what treatments you should keep an eye on.

What percentage of 2025 Q2 psychiatric pipeline news was positive vs negative? The news this quarter was overwhelmingly positive, with approximately 85.7% good news.

What disease states are most prominently featured in recent research? The top 4 disease states this quarter were schizophrenia (41.7%), major depressive disorder (25%), and treatment-resistant depression (16.7%), and suicidal depression (16.7%).

Check out all the specifics of our coverage from the from the first quarter below.

New NDA Submitted: Bysanti to Treat Acute Bipolar I and Schizophrenia

Vanda Pharmaceuticals submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) requesting marketing approval of milsaperidone (Bysanti, also known as VHX-896 and P-88) for the treatment of patients with acute bipolar I disorder and schizophrenia. The NDA is supported by several clinical studies assessing the efficacy and safety of Bysanti, which is an active metabolite of iloperidone, targets HTR2 and DRD2 receptors, and functions as an atypical antipsychotic. If approved, Bysanti could be available for sale in the US in 2026. Additionally, Vanda initiated a phase 3 clinical study for Bysanti as a once-daily adjunctive treatment for major depressive disorder in the fourth quarter of 2024. Results are expected in 2026.

Positive Interim Results on Trontinemab Validate Brainshuttle Technology for Alzheimer Disease Treatment

Trontinemab, a novel anti-amyloid monoclonal antibody that utilizes Brainshuttle technology, showed significant amyloid plaque reduction in patients with Alzheimer disease, prompting a phase 3 study. The Brainshuttle platform enables trontinemab to cross the blood-brain barrier, delivering higher antibody concentrations with reduced amyloid-related imaging abnormalities risk. Results from the phase 1B/2A Brainshuttle AD study showed that trontinemab achieved rapid and robust amyloid plaque reduction at low systemic doses.

MindMed Begins Phase 3 Emerge Study of MM120 in Patients With Major Depressive Disorder

MindMed recently announced that the first patient has been dosed in its phase 3 Emerge study evaluating MM120 ODT for treatment of major depressive disorder (MDD). MM120 ODT is a proprietary, pharmaceutically optimized form of lysergic acid diethylamide (LSD). The main goal of the Emerge study is to explore the change from baseline in MADRS score at week 6 between MM120 ODT 100 µg and placebo. The second MDD trial will depend on the progress from Emerge and further regulatory discussions. Topline data from Part A of the study is expected to be released in the second half of 2026.

Cybin Announces Partnership With Osmind to Advance Clinical-Stage Psychiatry Programs

Cybin, a late-stage breakthrough neuropsychiatry company, announced a strategic partnership with Osmind, a leading service provider advancing psychiatry through technology, services, and real-world evidence. Together, they will aim to bring innovative mental health treatments to patients in need. Cybin is currently developing 2 main potential treatments: CYB003, a deuterated psilocybin molecule, in phase 3 development for the adjunctive treatment of major depressive disorder (MDD) and CYB004, a proprietary deuterated N, N-dimethyltryptamine program in a phase 2 study for generalized anxiety disorder. The company also has a research pipeline of investigational, 5-HT-receptor focused compounds.

Cobenfy as Add-On Treatment for Schizophrenia Fails to Meet Primary Endpoint in Phase 3 ARISE Trial

According to topline results from the phase 3 ARISE study, xanomeline and trospium chloride (Cobenfy) as an adjunctive treatment to atypical antipsychotics did not show a statistically significant difference compared with placebo in adults with inadequately controlled symptoms of schizophrenia. However, treatment with Cobenfy and an atypical antipsychotic showed a numerical improvement compared with treatment with placebo and an atypical antipsychotic. Despite not meeting the primary endpoint, Cobenfy's safety profile and potential benefits suggest further investigation is warranted.

Transneural Therapeutics: A New Company to Develop Novel Neuroplastogens

A new preclinical-stage biotechnology company, Transneural Therapeutics, announced its launch on April 22, 2025. Transneural aims to transform the treatment of neuropsychiatric and neurodegenerative diseases with novel neuroplastogens, in particular recognizing the potential of 5-HT2A agonism to treat these conditions. The company's lead asset is TN-001, a dual 5-HT2A partial agonist/5-HT2B antagonist that aims to deliver antidepressant effects without hallucinations, potentially eliminating clinical supervision.

First-of-its-Kind Study: Using a Novel Platform to Assess Patients With Borderline Personality Disorder

Boehringer Ingelheim, the University of Oxford, and Cumulus Neuroscience teamed up for a first-of-its-kind study that will use the novel NeuLogiq neuroassessment platform to quantify brain activity, mood, and behavior at home in individuals who have been diagnosed with borderline personality disorder (BPD). Investigators hope to explore the acceptability of this novel technology and gain insights that could potentially guide future research and development of other new treatments. Participants include 30 young adults diagnosed with BPD and 20 young adults with no mental health diagnosis, who are observed using EEG and behavioral assessments to gather objective data. The platform's real-time data collection contrasts with traditional retrospective symptom recall, offering a more accurate picture of brain network activity.

FDA Filing Fee Waiver for New Drug Application of NRX-100 for Suicidal Depression

NRx Pharmaceuticals announced the grant of a filing fee waiver by the FDA to exempt NRx from a $4.3 million fee to file its New Drug Application for preservative-free ketamine (NRX-100). NRX-100 is a preservative-free formulation of intravenous ketamine for acute suicidal crises in depression. Currently available forms of ketamine contain the preservative benzethonium chloride, but its safety for repeated use has never been demonstrated. By applying for FDA approval to treat suicidal depression with NRX-100, NRX hopes to make this therapy available to all Americans seeking treatment and not just those who can pay out of pocket.

FDA Has Granted Request for End of Phase 2 Meeting to Discuss Alcohol Use Disorder Treatment, AD04

Adial Pharmaceuticals announced that the FDA granted Adial’s request for an end of phase 2 meeting to discuss a proposed clinical development plan and FDA guidance on the phase 3 adaptive with enrichment design of the upcoming clinical trial for AD04. The meeting will take place on July 25, 2025. AD04 is Adial’s lead investigational treatment, a genetically targeted selective serotonin-3 receptor (5-HT3) antagonist and therapeutic agent for the treatment of alcohol use disorder (AUD) in patients who engage in heavy drinking (defined as < 8 drinks/drinking day).

Phase 3 Development Plan for Evenamide as Add-On Therapy for Treatment-Resistant Schizophrenia

Newron Pharmaceuticals announced the approval of the pivotal ENIGMA-TRS phase 3 development program evaluating evenamide as an add-on therapy to current antipsychotics, including clozapine, in patients with treatment-resistant schizophrenia (TRS). This phase 3 development program consists of 2 pivotal studies: ENIGMA-TRS 1 and ENIGMA-TRS 2. ENIGMA-TRS 1 is an international, 52-week, randomized, double-blind, placebo-controlled phae 3 study evaluating the efficacy, tolerability, and safety of the 15 mg BID and 30 mg BID therapeutic doses of evenamide compared with placebo. ENIGMA-TRS 2 is a 12-week, randomized, double-blind, placebo-controlled phase 3 study, designed to evaluate the efficacy, tolerability, and safety of the 15 mg BID dose of evenamide in at least 400 participants.

New Ingrezza Data Demonstrates Functional and Quality of Life Improvements in Patients With Tardive Dyskinesia

Neurocrine Biosciences announced new analyses from a phase 4 randomized withdrawal study (NCT03891862) showing participants with tardive dyskinesia who received continued treatment with valbenazine (Ingrezza) capsules demonstrated functional and health-related quality of life improvements. The analyses were conducted using data from 127 participants in a phase 4, double-blind, placebo-controlled, randomized withdrawal study. Participants received up to 80 mg of Ingrezza for 8 weeks, then they were randomized to either continue receiving Ingrezza (n=59) or to receive placebo (n=59) for an additional 8 weeks. Those randomized to receive Ingrezza for an additional 8 weeks (week 16) saw continued improvements in all health-related quality of life dimensions, including significant improvements in mobility (placebo-adjusted difference from week 8: -0.34) and anxiety/depression (-0.38) compared with those receiving placebo.

Novel PDE10A Inhibitor for Acute Schizophrenia Exacerbation Presented at APA Annual Meeting

CPL’36, a PDE10A inhibitor, showed significant improvements in PANSS scores in a double-blind, randomized, placebo controlled, parallel group phase 2 study for acute schizophrenia exacerbation. At 4 weeks, investigators found improvement across all the studied PANSS scores. Specifically, patients receiving the 20 mg dose realized a 3.7 unit improvement from baseline (LS mean difference from placebo, P<0.001, Cohen’s d: 0.73) on the positive PANSS subscale score, while those participants in the 40 mg dose realized a 6.3 unit reduction (LS Mean difference from placebo, P <0.001, Cohen’s d: 1.38). Larger reductions were found on the total PANSS score at week 4 of treatment. Investigators recorded a 9.7 unit reduction from baseline for those patients who receives the 20 mg dose of CPL’36 when compared with placebo (LS mean difference from placebo, P <0.001, Cohen’s d: 0.77). Those who received the 40 mg dose demonstrated a 16.4 unit reduction (LS mean difference from placebo, P <0.001, Cohen’s d: 1.47).

Positive Phase 2 Results on NBI-1117568 for Schizophrenia Presented at 2025 ASCP Annual Meeting

Neurocrine Biosciences shared data from the phase 2 study of NBI-1117568 in adults with schizophrenia, which showed a significant improvement in symptoms and overall severity and highlighted new data on the safety and tolerability of the treatment. NBI-1117568 is the first and only investigational oral muscarinic M4 selective orthosteric agonist in clinical development as a potential treatment for schizophrenia. The study showed statistically significant improvements in PANSS total score with 20 mg of NBI-1117568 once daily by week 3 and at all subsequent visits through week 6. A statistically significant improvement was also observed by week 2 in the Clinical Global Impression of Severity scale, with continued improvement seen at all following visits through week 6.

New Data: Cariprazine Adjunctive to Antidepressant Therapy for Anhedonia Symptoms

According to new research, long-term open-label treatment with adjunctive cariprazine was associated with improvements in anhedonia for up to 26 weeks and suggest that long-term treatment with adjunctive cariprazine is safe and well tolerated, with potentially durable effects on anhedonia in patients with MDD. A 26-week, phase 3, open-label study demonstrated significant reductions in anhedonia subscale scores from baseline as early as week 4, sustained through week 26. Cariprazine was found to be safe and well tolerated, with the most common dose being 3 mg/day, followed by 1.5 mg/day and 4.5 mg/day.

FDA Officially Eliminates Clozapine REMS

On June 13, 2025, the FDA officially eliminated the clozapine REMS, and all REMS operations ceased. Although clozapine still carries a risk of severe neutropenia, the FDA has determined that the clozapine REMS is no longer necessary, and by eliminating the REMS, they expect to improve access to clozapine. In the wake of this decision, the Schizophrenia & Psychosis Action Alliance, in collaboration with the American Association of Psychiatric Pharmacists, has announced the upcoming development of a set of clinical, evidence-based courses designed to provide education and guidance for clozapine prescribing.

New Positive 12-Month Extension Data: Ecopipam for Tourette Syndrome in Pediatric Patients

Ecopipam for Tourette syndrome (TS) was found to be safe and effective in a 12-month, open-label extension of a phase 2b study. Ecopipam is a novel dopamine-1 receptor antagonist and first-in-class investigational compound that is being studied as a potential treatment for central nervous system disorders, including TS in pediatric patients. In a new study, ecopipam 1.8 mg/kg/day reduced tic severity and improved quality of life in children and adolescents with TS, with no evidence of tachyphylaxis. This is the largest study to date that examines the long-term safety and effectiveness of ecopipam in a pediatric population with TS.

NRx Pharmaceuticals Applies for FDA National Priority Voucher for Intravenous Ketamine (NRX-100)

A new formulation of ketamine is progressing through a novel FDA review pathway. The company has applied for a Commissioner’s National Priority Voucher for NRX-100, its patent-pending, preservative-free intravenous ketamine. NRx concurrently is preparing an NDA for the treatment of suicidal depression and PTSD. The company continues to anticipate an FDA decision on NRX-100 by the end of 2025.

COMP360 Psilocybin for Treatment-Resistant Depression: Positive Phase 3 Efficacy Data

Compass Pathways announced the successful achievement of the primary endpoint in the ongoing phase 3 COMP005 trial, the first of 2 phase 3 trials evaluating their synthetic, proprietary formulation of psilocybin for treatment-resistant depression (TRD), COMP360. COMP360 showed a statistically significant reduction in TRD symptom severity compared with placebo, with a clinically meaningful MADRS score difference. This trial is the first phase 3 study of synthetic psilocybin, marking a milestone in psychedelic research for mental health.

ALTO-203 Fails to Primary Efficacy Endpoint in Phase 2 Major Depressive Disorder Trial

Alto Neuroscience’s phase 2 investigational oral H3 receptor blocker, ALTO-203, failed to significantly improve mood in participants with MDD, missing its primary efficacy endpoint. Approximately 5 hours after a single dose of ALTO-203, participants reported significant improvements in alertness and mood; however, ALTO-203 failed to statistically separate itself from placebo. While the trial missed the endpoint, investigators reported significant changes in an EEG marker, the theta/beta ratio. This has been flagged as a way to identify individuals who might respond to treatment: patients with more abnormal theta/beta ratios at baseline had the biggest improvements in attention.

FDA Requires New Label Warning of Weight Loss Risk in Pediatric Patients Taking Extended-Release Stimulants for ADHD

The FDA announced it is revising the label of all extended-release stimulants indicated to treat attention-deficit/hyperactivity disorder (ADHD), including certain formulations of amphetamine and methylphenidate, to warn about the risk of weight loss and other adverse effects in patients younger than 6 years of age Although extended-release stimulants are not approved for children younger than 6 years, clinicians occasionally prescribe them off label to treat ADHD. According to analysis of data from clinical trials of extended-release formulations of amphetamine and methylphenidate for ADHD treatment, patients younger than 6 years have higher plasma exposures and higher rates of adverse effects than older children taking the same medication at the same dosage. Notably, investigators observed clinically significant weight loss in both short- and long-term studies with extended-release stimulants.

Positive Results From the Phase 2b Study of BPL-003 in Patients With Treatment-Resistant Depression

atai Life Sciences and Beckley Psytech today jointly announced positive topline results from the 8-week, quadruple-masked, dose-finding, core stage of the phase 2b clinical trial evaluating the efficacy and safety of a single dose of BPL-003 (intranasal mebufotenin (5-MeO-DMT) benzoate) in patients with TRD. The phase 2b clinical study is the largest controlled clinical study to investigate mebufotenin and the only blinded phase 2b study of mebufotenin to include the United States. BPL-003 demonstrated rapid, robust, and durable antidepressant effects with a single dose.

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