Phase 2 Study of CYC-126 for Treatment Resistant Depression Receives FDA Feedback, Will Proceed

Cyclerion Therapeutics, developers of CYC-126, received positive feedback from the US Food and Drug Administration (FDA) on the drug’s phase 2 study and path forward to potential regulatory approval.¹ The investigational drug is an anesthetic-based therapy incorporating live electroencephalogram (EEG) feedback to address treatment resistant depression.

The intended study is a randomized, double-blind, 2-part clinical study evaluating the drug in adults with treatment resistant depression who are also candidates for monitored anesthesia. 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. Cyclerion noted they believe guidance from the FDA will enable an Investigational New Drug submission in the future. A clinical advisory boardwas also formed, and will provide guidance regarding clinical development of CYC-126. Cyclerion had previously partnered with another organization, Medsteer, to integrate software to assist with real-time feedback in the treatment process. Chief operating officer of Medsteer, Nicolas Choussat, MSc, noted that “integrating intelligent software agents with real-time patient feedback holds great potential to improve clinical outcomes. We are thrilled to ramp up our work with Cyclerion Therapeutics in the field of neuropsychiatry and leverage our proprietary algorithms to help build the next generation of therapies.”²

“We are pleased with the constructive feedback received from the FDA, which provides additional clarity regarding CYC-126’s regulatory jurisdiction and development pathway,” commented Regina Graul, PhD, president and chief executive officer of Cyclerion. “This alignment supports our IND planning and affirms key elements of our proposed Phase 2 study design. We value the ongoing engagement with the applicable FDA divisions and believe this guidance provides an important foundation as we advance CYC-126 with the goal of addressing the significant unmet need in patients living with TRD,” she added.

CYC-126 is designed as a more individualized, precision-medicine approach, combining anesthetic agents with real-time EEG monitoring and algorithm-guided dosing. Developers of the drug noted that 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.

The phase 2 study is on track for initiation in the second half of 2026, with plans to enroll the first patients in Australia in 2026 and commence US enrollment in early 2027, the company noted.

References

1. Cyclerion Therapeutics announces progress toward CYC-126 phase 2 proof-of-concept study with FDA feedback and formation of clinical advisory board. Press release. February 17, 2026. Accessed February 17, 2026. https://www.globenewswire.com/news-release/2026/02/17/3239080/0/en/Cyclerion-Therapeutics-Announces-Progress-Toward-CYC-126-Phase-2-Proof-of-Concept-Study-with-FDA-Feedback-and-Formation-of-Clinical-Advisory-Board.html

2. Cyclerion Therapeutics announces strategic agreement with Medsteer and progress toward initiating phase 2 proof-of-concept study for CYC-126 in treatment-resistant depression. Press release. January 5, 2026. Accessed February 17, 2026. https://ir.cyclerion.com/news-releases/news-release-details/cyclerion-therapeutics-announces-strategic-agreement-medsteer