June 2026 in Review: Updates on the Psychiatric Treatment Pipeline

Take a look at this month’s developments in the psychiatric treatment pipeline. We compiled a recap of the latest news here, just in case you missed any of the updates.

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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