CYCN

Business Overview and Strategy We focus on building a pipeline of innovative therapeutics to address serious neuropsychiatric disorders with significant unmet medical need.
Our current strategic focus is centered on the development of a novel therapeutic approach for neuropsychiatric conditions, with the lead indication being treatment-resistant depression (“TRD”), which we believe represents a substantial clinical and commercial opportunity.
Primary Focus on New Potential Treatment for Treatment Resistant Depression (“TRD” ) Over the past year, we have refined our strategic direction toward programs that combine established pharmacologic agents with enabling technologies designed to improve precision, reproducibility, and patient outcomes.
As part of this strategy, Cyclerion has evaluated multiple opportunities and prioritized CYC-126, an individualized therapy for TRD as our foundational development program. • In September 2025, we entered into a license agreement with the Massachusetts Institute of Technology (“MIT”) for intellectual property supporting this program (the “MIT License Agreement”).
Under the terms of the MIT License Agreement, MIT will be eligible to receive up to $ 4.4 million upon the achievement of certain development, regulatory and sales milestone payments.
MIT will also receive tiered royalties in a range of percentages in the low single digits based on future net sales of licensed products as set forth in the MIT License Agreement.
Further, we are required to pay MIT varying percentages of income received as consideration for any sublicenses granted. • In January 2026, we entered into a collaboration and option-to-license agreement with Medsteer SAS (“Medsteer”) to access certain technology, data assets, and technical know-how related to drug delivery and physiological monitoring.
Under the terms of the Collaboration Agreement, the Company will pay to Medsteer a nominal upfront payment, a payment upon exercise of the Option, and Medsteer will be eligible to receive up to $ 3.7 million upon the achievement of certain development, regulatory and sales milestone payments.
Medsteer will also receive an annual royalty payment and royalties in a percentage in the low single digits based on future net sales of licensed products, subject to certain adjustments as set forth in the Collaboration Agreement. • We are advancing development planning, regulatory strategy, and commercial positioning for this program and intend to initiate a Phase 2 proof-of-concept study in Australia in the second half of 2026. • In February 2026, we received notice from the FDA confirming prior informal communications that CYC-126 will be regulated under the FDA’s Center for Drug Evaluation and Research (“CDER”), with the FDA’s Center for Devices and Radiologic Health (“CDRH”) providing input and reviews as applicable.
We believe that the FDA feedback provided clear guidance that the Company believes will help enable an FDA IND submission.
The FDA guidance supported continued advancement of the planned Phase 2 study design, leveraging FDA-approved anesthetics and their well-established nonclinical and clinical safety data. • As a result, we expect to remain on track to initiate the Phase 2 study in the second half of 2026, with the first patient anticipated to be enrolled in Australia and U.S. enrollment expected to commence in the first half of 2027. • We have also recently 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.
This advisory board will provide strategic guidance and support key decision making regarding clinical development as Cyclerion seeks to advance CYC-126 for TRD and builds a pipeline across neuropsychiatric diseases.
CYC-126 is being developed as a potential anesthetic-based therapy for neuropsychiatric indications, including TRD.
The system is designed to deliver anesthetic agents while monitoring brain activity to support individualized dosing through a patient feedback loop.
The Company believes this approach may provide a differentiated treatment option for patients with TRD.
CYC-126 consists of two generic intravenous anesthetic agents, propofol and dexmedetomidine, administered through a personalized delivery system intended to operate as a clinical decision support tool for an anesthesiologist.
The treatment is expected to be delivered in a hospital-based setting, such as a procedure room or post-anesthesia care unit (“PACU”), followed by a short recovery period in the PACU.
Major depressive disorder (“MDD”) is a prevalent psychiatric illness characterized by episodes of depressed mood, cognitive disturbances, and diminished interest or pleasure in activities lasting for at least two weeks.
A subset of patients with MDD who do not achieve an adequate response after at least two antidepressant treatments are considered to have treatment-resistant depression.
It is estimated that more than one-third of patients with medication-treated MDD meet criteria for TRD, representing approximately 2.8 to 3 million adults in the United States.
Patients with TRD experience higher hospitalization rates, increased suicide risk, greater psychiatric comorbidity, and limited effective treatment options.
Cyclerion’s development strategy for CYC-126 is intended to leverage existing clinical knowledge and safety data associated with approved anesthetic agents while integrating technology-enabled monitoring and delivery capabilities.
We believe this integrated approach may support differentiated clinical performance and scalability in hospital-based treatment settings; however, substantial development, regulatory review, and investment will be required before commercialization, if any.
Propofol and dexmedetomidine have an established clinical safety database as widely used anesthetic agents.
Additionally, several early-phase clinical studies have suggested that propofol may have rapid-acting antidepressant effects in patients with TRD.
Cyclerion is developing CYC-126 to incorporate a proprietary, technology-enabled delivery approach designed to achieve and maintain specific electroencephalogram (“EEG”) states.
The Company believes that controlled sedation may modulate communication among brain regions that are dysregulated in patients with TRD.
Cyclerion expects to initiate a multinational proof-of-concept, double-blind randomized controlled trial of CYC-126.
The study is expected to be conducted in two parts, with the first portion focused on safety and pharmacodynamic effects and the second portion focused on safety and efficacy.
The Company currently estimates that the first portion of the study could commence in the second half of 2026 and that both portions of the study could be completed over the subsequent two years.
In parallel with the advancement of our neuropsychiatric strategy, Cyclerion continues to evaluate opportunities related to our legacy soluble guanylate cyclase (“sGC”) stimulator assets, including potential collaborations, monetization opportunities, or other strategic transactions intended to maximize shareholder value.
To support execution of our strategy, we intend to seek additional capital through equity or other financing transactions.
In February 2025, our registration statement on Form S-3 (the “Shelf Registration”) was declared effective by the U.S.
Securities and Exchange Commission, providing flexibility to access the capital markets, subject to market conditions and other factors.
Under current SEC regulations, because the aggregate market value of our common stock held by non-affiliates is less than $75 million, the amount of securities we may sell under the Shelf Registration during any twelve-month period is limited to one-third of the aggregate market value of our voting and non-voting common equity held by non-affiliates.
In addition to the Shelf Registration, we are also seeking to raise capital to begin Phase 2 trials and for general working capital purposes.
There can be no assurance that our efforts to raise capital will be successful, in which event we would have to delay or abandon our plans to implement our strategy for the CY-126 program.
Cyclerion operates with a lean organizational structure and utilizes a combination of internal leadership and external consultants to advance our programs while managing operating expenses.
Regina Graul, Ph.D., was appointed Chief Executive Officer and Director in August 2024 after previously serving as President.
Rhonda Chicko serves as Chief Financial Officer.

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Business Overview and Strategy Our strategy for Cyclerion is to build a new pipeline with therapeutics to treat certain neuropsychiatric diseases.
Over the past year, Cyclerion’s diligence team which is composed of committed external experts and internal personnel in their respective fields, have been conducting asset evaluations in many therapeutic areas.
Throughout this process, the team identified and assessed dozens of products and other opportunities directed at addressing patient’s needs and increasing shareholder value.
The team prioritized an individualized therapy for treatment resistant depression (“TRD”) as our foundational product candidate and we have entered into a non-binding option to license agreement for the intellectual property associated with this product.
With the large unmet medical need in TRD, the clinical development stage of this asset, and the strong commercial opportunity, we believe that this product is well suited to be the foundation moving forward for Cyclerion.
The program team is currently developing an integrated development and commercial strategy in TRD.
In addition to significantly reducing operating expenses and the potential to obtain revenues from our legacy soluble guanylate cyclase (sGC) stimulator clinical assets, we intend to raise funds to support the execution of the product plans in TRD.
As such, we have developed a financing strategy plan and recently filed a registration statement on Form S-3 (the “Shelf Registration”) with the Securities and Exchange Commission (the “SEC”) which would allow us to sell registered shares of our common stock if we choose to do so.
The Shelf Registration was declared effective by the SEC in February 2025.
We continue to build our infrastructure, and Regina Graul, Ph.D. was promoted to Chief Executive Officer (CEO) and Director to our Board in August of 2024 after she was hired as President in late 2023.
Graul has significant experience in research and development, product search and evaluation and has extensive knowledge growing and leading integrated high-functioning teams.
We also retained as our Chief Financial Officer, Rhonda Chicko, who has extensive experience working with early and later-stage drug development companies.
To limit our operating expenses, we have used consultants (including Ms.
Chicko) rather than hiring additional full-time employees; Dr.
Graul is the only current employee to date.
Our goal is to hire additional C-suite executives later this year.
Since that time, our strategy for Cyclerion has changed and our sGC assets zagociquat and CY3018 were sold in 2023 to Tisento, we out-licensed praliciguat in 2021 and we have entered into a non-binding license option agreement for olinciguat in 2024.
We are leveraging our legacy sGC stimulator assets with the goal of generating revenues which, if realized, will be used to help fund our strategic building plan and provide value to our stockholders.
The following table is a high-level summary of our historical sGC portfolio: Program Indication(s) Description Status Zagociguat (CNS-penetrant) MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome), cognitive impairment Zagociguat is a CNS-penetrant sGC stimulator that has shown rapid improvements across a range of endpoints reflecting multiple domains of disease activity, including Sold to Tisento as part of the Asset Purchase Agreement in July 2023.
On January 27,2025, Tisento announced dosing the first participant in their associated with schizophrenia, and Alzheimer's Disease with Vascular Pathology (ADV) mitochondrial disease-associated biomarkers.
Phase 2b study evaluating Zagociguat in MELAS.
Sold to Tisento as part of the Asset Purchase Agreement in July 2023 Olinciguat (peripheral) Cardiovascular diseases Olinciguat is a vascular sGC stimulator Cyclerion entered into an exclusive non-binding license option agreement with a separate entity, wholly-owned by CVCO Therapeutics, Inc. in July 2024 Praliciguat (peripheral) Focal Segmental Glomerulosclerosis (FSGS) Praliciguat is a systemic sGC stimulator that is licensed to Akebia for the treatment of a rare kidney disease.
Research and Development Programs The following table presents the status of sGC stimulator assets that are either licensed or optioned to other entities: Akebia License Agreement On June 3, 2021, we entered into a License Agreement with Akebia (the “Akebia License Agreement”) relating to the exclusive worldwide license to Akebia of our rights to the development, manufacture, medical affairs and commercialization of pharmaceutical products containing the pharmaceutical compound known as praliciguat and other related products and forms thereof enumerated in the Akebia License Agreement.
We are eligible to receive additional milestone cash payments of up to approximately $558.5 million in total related to potential future development, regulatory, and commercialization milestone payments for praliciguat.
In 2021, Akebia paid a $3.0 million upfront payment to us upon signing of the Akebia License Agreement, and subsequently paid us an additional $1.25 million in December 2024 and is obligated to pay us an additional $0.5 million in September 2025.
Olinciguat Option to License with CVCO Therapeutics, Inc.
(CVCO) Olinciguat is a Phase 2, orally administered, once-daily, vascular sGC stimulator.
On July 22, 2024, we entered into an Option to License Agreement (the “Option Agreement”) with a third party (the “Optionee”), pursuant to which the Optionee has an option (the “Option”) to enter into an exclusive license to olinciguat for human therapeutics, subject to certain carveouts.
Under the terms of the Option Agreement, the Optionee paid us an Option fee of $150,000 in August 2024.
The Optionee may exercise the Option on or before March 20, 2025, which may be extended for an additional two-month period for an additional fee of $ 25,000 .
If the Optionee exercises the Option during the Option Period, the Parties shall promptly commence negotiations of the definitive license agreement.
The terms of the license agreement will be negotiated in good faith within a period not to exceed 90 days after the date of exercise of the Option.
If the parties cannot reach agreement, all rights revert to us.
In addition, the Optionee has agreed to reimburse us for certain patent expenses incurred during the Option period.
Upon the closing on July 28, 2023 following receipt of approval by the Cyclerion stockholders of the transactions contemplated by the Asset Purchase Agreement, we sold to Tisento the Transferred Assets and Tisento assumed certain liabilities relating thereto, including, but not limited to (i) liabilities, costs and expenses arising after the date of the Asset Purchase Agreement relating to the employment of certain Cyclerion employees and the conduct of certain preclinical and clinical trial activities prior to the closing of the transactions contemplated by the Asset Purchase Agreement, and (ii) liabilities relating to such assets to the extent relating to the period after the closing of the transaction.
In consideration for such sale and assumption, at the closing we received proceeds of $8.0 million as cash consideration, $2.4 million as reimbursement for certain operating expenses related to such assets for the period between signing and closing of the Asset Purchase Agreement, and shares of common stock of Tisento Parent comprising 10% of the then issued and outstanding equity securities of Tisento Parent immediately following such closing, subject to certain protections against dilution.
On January 27, 2025, Tisento Therapeutics announced that the first patient has been dosed in its global Phase 2b PRIZM study.
ClinicalTrials.gov (NCT06402123) for more information.
We have 20 issued U.S. patents, 11 pending U.S. patents applications and numerous foreign patents and pending patent applications related to our sGC programs.
Patent families are filed either as utility U.S. patents or under an international patent law treaty (PCT) that provides a unified procedure for filing a single initial patent application to seek patent protection for an invention simultaneously in each of the 157 contracting states, followed by the process of entering national phase, which requires a separate application in each of the member states in which national patent protection is sought.

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