Cyclerion Receives Positive FDA Feedback on CYC-126 Phase 2 Study for Treatment-Resistant Depression

Cyclerion Therapeutics received positive written regulatory feedback from the US Food and Drug Administration on CYC-126's Phase 2 proof-of-concept study in treatment-resistant depression and its path to potential regulatory approval. The investigational drug is an anesthetic-based therapy incorporating live electroencephalogram (EEG) feedback to address treatment-resistant depression.

The planned study is a randomized, double-blind, two-part clinical study evaluating CYC-126 in adults with treatment-resistant depression who are candidates for monitored anesthesia. Participants will be randomized to either active treatment or sham control arms to assess safety, antidepressant efficacy, and durability of response. The trial will use FDA-accepted clinical endpoints, including the Montgomery-Asberg Depression Rating Scale, and will assign participants randomly to treatment or placebo groups. Assessments of safety, efficacy, and durability of response will be the main focus.

The study will be regulated under the FDA Center for Drug Evaluation and Research, with the FDA Center for Devices and Radiologic Health providing input and review where applicable. The FDA feedback provided clear guidance that the Company believes will help enable an FDA Investigational New Drug submission. The FDA supported continued advancement of the planned Phase 2 study design, leveraging FDA-approved anesthetics and their well-established nonclinical and clinical safety data.

The president and chief executive officer of Cyclerion commented that the constructive feedback received from the FDA provides additional clarity regarding CYC-126's regulatory jurisdiction and development pathway. The alignment supports IND planning and affirms key elements of the proposed Phase 2 study design. The executive added that the company values the ongoing engagement with the applicable FDA divisions and believes this guidance provides an important foundation as they advance CYC-126 with the goal of addressing the significant unmet need in patients living with treatment-resistant depression.

CYC-126 is designed as a more individualized, precision-medicine approach, combining anesthetic agents with real-time EEG monitoring and algorithm-guided dosing. Cyclerion believes this strategy may enable clinicians to more precisely guide patients toward target brain states associated with antidepressant effects, offering a new option for patients seeking alternative therapies for treatment-resistant depression. The incorporation of real-time EEG monitoring and algorithm-guided anesthetic titration represents an effort to standardize and potentially optimize neurophysiological targets associated with antidepressant response. If validated, this model could complement existing neuromodulation strategies, such as electroconvulsive therapy and transcranial magnetic stimulation, by offering a pharmacologically mediated yet brain-state-guided intervention delivered in a monitored setting.

Cyclerion also announced the formation of a Clinical Advisory Board with the appointment of five internationally recognized key leaders in neuropsychiatry, anesthesiology clinical care, and clinical development. The Clinical Advisory Board will provide strategic guidance and support key decision making regarding clinical development as Cyclerion advances CYC-126 for treatment-resistant depression and builds a pipeline across neuropsychiatric diseases. The chief executive officer stated that these accomplished leaders bring a powerful combination of neuropsychiatric, anesthesiology, and clinical development expertise that will help guide the advancement of CYC-126 and inform the continued expansion of the pipeline.

Cyclerion had previously partnered with Medsteer to integrate software to assist with real-time feedback in the treatment process. The chief operating officer of Medsteer noted that integrating intelligent software agents with real-time patient feedback holds great potential to improve clinical outcomes, and that the company is thrilled to ramp up work with Cyclerion Therapeutics in the field of neuropsychiatry and leverage proprietary algorithms to help build the next generation of therapies.

In addition to receiving feedback from the FDA and forming the Clinical Advisory Board, Cyclerion has continued to advance its clinical development activities, including the selection of a contract research organization to support execution of the planned multinational study. The company remains on track to initiate the Phase 2 study in the second half of 2026, with the first patient to be enrolled in Australia and US enrollment commencing in the first half of 2027.