The Psychiatric Pipeline in Review: Quarter 2, 2026

The first quarter of 2026 had several prominent developments 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.

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

Phase 3 Brilliance Studies Initiated on Alixorexton for the Treatment of Narcolepsy Type 1 and Type 2

At the beginning of the month, Alkermes announced the initiation of the Brilliance Studies, a phase 3 program evaluating the safety and efficacy of alixorexton compared with placebo in adults with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, NT2, and idiopathic hypersomnia (IH).

LPCN 1154 for Postpartum Depression Fails to Meet Phase 3 Primary Endpoint

Topline results from Lipocine’s phase 3 placebo-controlled trial evaluating oral brexanolone (LPCN 1154) for the treatment of postpartum depression. LPCN 1154 did not show a statistically significant reduction from baseline in Hamilton Depression Rating Scale (HAM-D) 17-item total score compared with placebo at hour 60 in the full analysis set, thus failing to meet the primary endpoint.

GlyphAgo for Treatment of Anxiety Shows Positive Phase 1 Topline Results

GlyphAgo (SPT-320), a modified form of agomelatine, showed proof-of-concept in topline phase 1 results. The drug attained therapeutic levels of agomelatine at lower doses than unmodified agomelatine, reducing potentially harmful liver exposure and the need for liver testing.

Encouraging Pharmacodynamic Data From Phase 2 Clinical Trial of AL001

Alzamend Neuro today announced encouraging pharmacodynamic findings from a brain magnetic resonance spectroscopy (MRS) analysis conducted in healthy participants (N=6) in a clinical trial of AL001 conducted at Massachusetts General Hospital. AL001 is a patented ionic cocrystal formulation of lithium combined for delivery with L-proline and salicylate, designed to deliver a full therapeutic amount of lithium to the brain with less systemic exposure than lithium carbonate. It is currently being studied as a treatment for Alzheimer disease, bipolar disorder type 1, major depressive disorder, and posttraumatic stress disorder.

First Participants Enrolled in Phase 2a Study of BXCL501 for Treatment of Acute Stress Reactions

BioXcel Therapeutics announced the enrollment of the first participants in a US Department of War-funded phase 2a clinical trial evaluating sublingual dexmedetomidine (BXCL501) for the treatment of acute stress reactions (ASR), also known as acute stress disorder. The double-blind, placebo-controlled trial is designed to enroll 100 participants experiencing ASRs following motor vehicle collisions and will investigate the potential of BXCL501 to reduce ASR symptom severity, improve neurocognitive function, and prevent the progression to chronic posttraumatic neuropsychiatric symptoms.

BPL-003 for Treatment Resistant Depression Continues to Show Sustained Symptom Reduction

Results of part 2 from the phase 2a study pf BPL-003 for treatment-resistant depression showed rapid and sustained reductions in symptoms. The data included participants taking selective serotonin reuptake inhibitors (SSRIs), and part 2 analysis has been published in CNS Drugs. The phase 2a study was a 12-week open-label, ascending-dose trial with 12 adult participants aged 18 to 75 with moderate to severe major depressive disorder and treatment-resistant depression. The severity of the disorder was classified by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 24 or higher. All participants had a history of 2 or more failed courses of antidepressants and continued on a stable dose of an SSRI (citalopram, escitalopram, sertraline, or fluoxetine) throughout the study. Half of participants received a single 10 mg dose of BPL-003, while half received a single 12 mg dose. Participants were then monitored for 12 weeks.

Lybalvi Associated With Improvement in Negative Symptoms of Schizophrenia: Findings From Long-Term Analysis

This month, Alkermes announced the publication of a 56-week post hoc analysis of the effects of olanzapine and samidorphan (Lybalvi) on negative symptoms in adults living with schizophrenia, which found that treatment with Lybalvi was associated with significant and durable improvement in mean negative symptom scores. Lybalvi is currently approved in the US for the treatment of schizophrenia in adults, for the treatment of bipolar I disorder in adults, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, and as monotherapy or as adjunct to lithium or valproate.

New US Grant Program Announced for Post-Approval COMP360 Provider Training

Compass Pathways today announced an invitation for US based organizations to apply for a grant to create training content for health care providers who want to be able to deliver investigational COMP360 psilocybin treatment, if COMP360 is approved. While many high-quality training organizations have already trained thousands of health care providers in core and psilocybin-specific psychedelic care, this particular grant program will support the development of high-quality training content, including a COMP360-specific module, with the aim of ensuring health care providers are well-prepared to care for patients receiving COMP360 following its potential commercial launch.

Ongoing Trial for PBFT02 Shows Improvement of Frontotemporal Dementia With Granulin Mutations

Updated phase 1/2 clinical trial data on PBFT02, a cerebrospinal fluid injection, shows slowed neurodegeneration in patients with frontotemporal dementia with granulin mutations. A recent type C meeting with developers, Passage Bio, and the FDA recommended a randomized controlled trial of the medication as a next step, which the company has not confirmed due to ethical and logistical questions.

New AAN Poster Presentation on Alixorexton for Narcolepsy Type 1: Improvement in Disease Severity, Cognitive Functioning, and Fatigue

In a poster presentation at the American Academy of Neurology (AAN) 2026 Annual Meeting, investigators presented additional data from the Vibrance-1 phase 2 study of alixorexton in patients with narcolepsy type 1 (NT1). According to the results, participants with NT1 taking once-daily alixorexton demonstrated nominally significant, clinically meaningful improvements in patient-reported disease severity, cognitive impairment, and fatigue, with improvements sustained through 12 to 13 weeks. Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH).

EMP-01 for Social Anxiety Disorder Demonstrates Meaningful Improvements in Phase 2a Study

AtaiBeckley announced expanded phase 2a results for oral R-MDMA (EMP-01) in adults with social anxiety disorder (SAD), which show that EMP-01 demonstrated clinically meaningful and consistent improvements across clinician-rated symptoms, patient-reported experience, and real-world behavioral outcomes. The multi-center study enrolled 71 adult participants with moderate-to-severe SAD across 7 clinical sites in the UK. Participants were randomly assigned to receive 2 in-clinic administrations of EMP-01 (225 mg) or placebo, given 28 days apart, with no adjunctive psychotherapy; 70 participants received at least 1 dose of study drug and 69 completed the day 43 efficacy assessments. All clinician-rated assessments were conducted by blinded central raters. Topline results from this study were previously reported in February 2026.

FDA Fast-Tracks Psychedelic Therapies for Depression, PTSD, and Alcohol Use Disorder

The FDA announced a series of regulatory actions aimed at accelerating development of psychedelic-based treatments for serious mental illness following the recent executive order directed at the US Department of Health and Human Services. The moves include issuance of priority review vouchers, clearance of new early-phase clinical research, and forthcoming guidance on trial design for serotonin-2A agonists and related compounds. The actions signal a notable escalation in federal support for investigational therapies for psychiatric disorders where current pharmacological options are lacking.

FDA Approves sNDA of Caplyta for the Prevention of Relapse in Schizophrenia

The FDA has approved a supplemental New Drug Application based on long-term data evaluating the safety and efficacy of Johnson & Johnson’s lumateperone (Caplyta) for the prevention of relapse in schizophrenia, further reinforcing the long-term efficacy and tolerability of Caplyta. In the phase 3, double-blind, randomized withdrawal trial supporting this update, Caplyta significantly extended time to relapse vs placebo during the 26-week double-blind treatment period (P=0.0002), helping support long-term stability for adults living with schizophrenia. Participants treated with Caplyta had a 63% lower risk of relapse compared with placebo (hazard ratio = 0.37), and 84% of participants were relapse-free over 6 months. Caplyta also significantly delayed time to all-cause treatment discontinuation, including relapse.

AD04 Application Submitted to FDA Commissioner’s National Priority Voucher Pilot Program for Potential Expedited Review

Adial Pharmaceuticals has announced the submission of the AD04 product application for consideration of the FDA Commissioner’s National Priority Voucher Pilot Program (CNPV). The CNPV program was announced in June 2025 and is designed to speed up the FDA review process for drugs that address 1 of 5 key US national health priorities. The program also utilizes a collaborative review approach, where experts meet to discuss cases and help evaluate applications more efficiently.

Patent Issued for Novel Genetic Biomarker DGM4: Identified Through Liafensine Program for Treatment-Resistant Depression

The United States Patent and Trademark Office has issued patent number 12,612,261, titled “Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters,” for the use of Denovo Biopharma’s DGM4. DGM4 is a novel genetic biomarker discovered through Denovo’s artificial intelligence and big data based Denovo Genomic Marker platform for the liafensine (DB104) program for treatment-resistant depression.

FDA Approves Auvelity for Treatment of Agitation in Alzheimer Disease

The FDA has approved Axsome Therapeutics’ oral dextromethorphan-bupropion (Auvelity, formerly known as AXS-05) for the treatment of agitation associated with Alzheimer disease (AD). Auvelity is a first-in-class treatment for AD agitation which targets the N-methyl D-aspartate (NMDA) and sigma-1 receptors.

Lumateperone Ranks Highest Among Adjunctive MDD Therapies in First Network Meta-Analysis

Johnson & Johnson announced findings from the first network meta-analysis (NMA) comparing lumateperone (Caplyta) with other FDA-approved atypical antipsychotics used as add-on treatment for adults with major depressive disorder (MDD). Presented as a late-breaking poster at the 2026 Neuroscience Education Institute Spring Congress in Kissimmee, Florida, the analysis found lumateperone ranked highest across 4 key efficacy measures and demonstrated a favorable tolerability profile, particularly with respect to weight, when compared with the other agents evaluated. The new analysis ranked lumateperone the best for adjunctive MDD symptom relief, with minimal weight gain vs other atypical antipsychotics.

FDA Clears Clinical Trial of NRX-101 in Combination with Robotic-Enabled TMS in Patients With Depression and Suicidality

The FDA cleared NRx Pharmaceuticals to initiate a clinical trial of NRX-101 (D-cycloserine/lurasidone fixed dose combination) vs placebo in patients with depression and suicidality who are being treated with either robotic-assisted transcranial magnetic stimulation (TMS) or sham TMS. The placebo-controlled phase 2/3 trial is identified as “A Randomized, Double-Blind, Three-Arm Study of NRX-101 as Adjunctive Therapy to Active or Sham Transcranial Magnetic Stimulation in Adults with Treatment Resistant Major Depressive Disorder (MIND1).” Preliminary research suggests that D-cycloserine significantly enhances the effect of TMS, with a greater than 2-fold benefit of reduction in symptoms of depression.

Phase 2 MINDFul Trial Results on XPro1595 for Early Alzheimer Disease With Inflammation

INmune Bio announced that results from its phase 2 MINDFuL trial that evaluated the safety, biomarker engagement, and clinical efficacy of XPro (XPro1595, pegipanermin) in patients with mild Alzheimer disease (AD) characterized by biomarkers of inflammation. In a prespecified analysis of the protocol-defined AD with inflammation subgroup, XPro showed directionally consistent benefit across cognitive, global, functional, behavioral, and biomarker endpoints over 24 weeks, with no amyloid-related imaging abnormalities observed. However, XPro1595 did not show statistical significance on the primary endpoint within the overall study population.

SYT-510 for Generalized Anxiety Disorder: Phase 2 Trial Dosing Initiated

Synendos Therapeutics announced it has started dosing in its phase 2 efficacy and safety clinical trial of SYT-510 in patients with the diagnosis of generalized anxiety disorder (GAD). The trial will investigate the efficacy, safety, tolerability and pharmacokinetics of a single dose of SYT-510 in participants meeting DSM-5 diagnostic criteria for GAD. SYT-510 belongs to a novel class of endocannabinoid system (ECS) modulators called selective endocannabinoid reuptake inhibitors (SERIs), which represent first-in-class, new chemical entities that modulate the ECS through a self-limiting mode of action. This study marks the first time a SERI molecule will be dosed in a patient population.

GLP-1s For Treatment of Alcohol Use Disorder: Current and Future Directions

GLP-1 agents appear to attenuate the wanting, craving, and pleasure experience associated with both food and substances of abuse, potentially interrupting core reinforcement cycles that drive compulsive use. While clinical evidence continues to accumulate, the convergence of mechanistic plausibility, epidemiologic signal, and futures of trial data frames GLP-1 receptor agonists with potential in addiction pharmacotherapy.

Phase 3 Program Investigating COMP360 Psilocybin for Treatment-Resistant Depression: Breaking Poster Data From the 2026 ASCP Annual Meeting

Compass Pathways shared late-breaking poster data at the 2026 ASCP Annual Meeting in Miami, FL, on their phase 3 program investigating COMP360 psilocybin for treatment-resistant depression. Study COMP005 compared a 25 mg dose with a placebo over 26 weeks and 2 doses (1, 10, or 25 mg) against each other. Both studies COMP005 and COMP006 showed highly statistically and clinically significant results, with significant improvements in the Montgomery-Åsberg Depression Rating Scale score. The cohort included patients with severe depression and many lifetime depressive episodes and chronic current episodes. Investigators also noted that 2 treatments were generally better than 1, and that some patients benefited dramatically from a single treatment. These studies aimed to address skepticism by recruiting a valid population without prior psychedelic use and by conducting rigorous, large-scale trials.

FDA Grants De Novo Approval to Modius Spero, Neuromodulation Device for PTSD

The FDA has granted de novo approval to Neurovalens’ Modius Spero, a neuromodulation device to treat symptoms associated with posttraumatic stress disorder (PTSD). This is the first neuromodulation device to receive FDA authorization to treat symptoms associated with PTSD. The device uses low-level electrical stimulation to target specific areas of the brain to address the symptoms of PTSD. The FDA’s de novo classification is a pathway designed for new medical devices that have been proven safe and effective for their intended use through clinical testing.

FDA Issues CRL for CTx-1301 for Treatment of ADHD

The FDA has issued a Complete Response Letter in response to the New Drug Application (NDA) for CTx-1301, a novel formulation of dexmethylphenidate for treatment of attention-deficit hyperactivity disorder (ADHD). The FDA’s letter requested specific information about chemistry, manufacturing, and controls, without raising concerns about safety or efficacy of the medication.

Cingulate submitted a New Drug Application (NDA) for CTx-1301 to the FDA in July 2025 and received approval in October 2025, which set the FDA action date for the end of May 2026, culminating in issuance of the CRL in early June.⁴ CTx-1301 was reviewed via the FDA 505(b)(2) regulatory pathway, a path that allows reference to existing data on previously approved active ingredients while demonstrating novel clinical benefit through a differentiated delivery mechanism.

New Positive Phase 2 Topline Data on Elunetirom for the Treatment of Bipolar Depression

Autobahn Therapeutics announced positive topline data from its phase 2 AMPLIFY-BD trial evaluating elunetirom as an adjunctive treatment in patients with bipolar I or bipolar II depression. Elunetirom achieved statistical significance across the primary and all key secondary depression endpoints, demonstrating clinically meaningful antidepressant effects with a favorable safety profile.

Elunetirom is a novel, oral, once daily, brain-penetrant CNS thyroid hormone receptor agonist. These data provide the first clinical evidence for CNS-targeted thyroid hormone receptor agonism, which isa differentiated mechanism designed to directly enhance brain energy metabolism and neuroplasticity.

Developing Next-Generation Psychedelic Treatments: Insights on Bretisilocin From AJ Cannon, MD

In 2025, AbbVie acquired Gilgamesh Pharmaceuticals’ lead asset, bretisilocin (GM-2505), a potential best-in-class compound for the treatment of major depressive disorder (MDD).¹ Positive topline results from a phase 2a study showed that bretisilocin led to a clinically impactful and statistically significant reduction in severity of depressive symptoms when compared with a low dose active comparator, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. AJ Cannon, the senior medical director in Neuroscience Clinical Development at AbbVie, shared more about this novel treatment and the evolving psychedelic landscape.

Positive Topline Results From Phase 3 Emerge Study of DT120 ODT in Major Depressive Disorder

Definium Therapeutics today announced positive topline results from phase 3 study Emerge evaluating a single dose of DT120 (lysergide) ODT 100 µg in adults with major depressive disorder (MDD). Notably, the study met primary and all key secondary efficacy endpoints. Emerge was a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of a single 100 µg dose of DT120 ODT vs placebo in adult participants with MDD. Robust antidepressant signal was observed at week 6 with an -8.1-point placebo-adjusted MADRS difference (P<0.0001), meeting the primary endpoint in a randomized, double-blind design.

FDA Issues CRL for Cytisinicline for Smoking Cessation in Adults

The FDA has issued a Complete Response Letter (CRL) for cytisinicline for smoking cessation in adults. The CRL identified manufacturing concerns, with no deficiency in clinical safety or efficacy of the drug. The CRL response cited outstanding manufacturing-related issues from an inspection of a third-party manufacturing facility, as well as final product labeling that was not completed by the FDA action date. Achieve Life Sciences, developers of the drug, noted that the manufacturing practice issues are not specific to cytisinicline and are related to general manufacturing at the facility. The company intends to resubmit the NDA with updated manufacturing information.

Phase 2 Analysis of ML-004 for Autism Spectrum Disorder Fails to Meet Endpoint

Prespecified analysis of a phase 2 trial for ML-004 in autism spectrum disorder showed no significant change in social communication deficits, but a meaningful improvement in irritability. The phase 2 IRIS trial did not meet its primary endpoint for change in social communication scores, but the drug was generally well-tolerated.

The phase 2 double-blind, placebo-controlled study was designed for exploratory signal finding, testing multiple clinical endpoints including social communication and irritability. A primary endpoint for social communication was measured from baseline to week 12 by the caregiver-reported Autism Behavioral Inventory (ABI) Social Communication Domain score. Both adolescent and adult participants (aged 12 to 45) were included, with 161 total participants and 26 in the specified analysis. Participants received either placebo or 12, 24, 48, or 72 mg doses of ML-004 once daily.

New Positive Data From Largest Real-World Study of Deep TMS in Patients With Comorbid PTSD and MDD

BrainsWay announced the presentation of positive new real-world data demonstrating significant improvements in patients with comorbid posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) treated with deep transcranial magnetic stimulation (Deep TMS). PTSD symptom improvement was substantial, with 83.5% meeting response criteria and an average 52% reduction in PCL-5 scores following treatment. Depression outcomes were clinically meaningful, including 66.6% response, 27.3% remission, and an average 50% reduction in PHQ-9 scores.

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