What changed in this filing

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Item 1. Business

2026-03-30 compared with 2025-03-04 · 212 added, 154 removed, 1115 unchanged (25% of the section changed)

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;

Graul is the only current employee to date.

Our goal is to hire additional C-suite executives later this year.

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.

We may expand our leadership team and operational capabilities over time as our development programs advance.

We were founded in 2018 to focus on the treatment of serious diseases with novel sGC stimulators in both the central nervous system (CNS) and the periphery.

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.

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.

We also entered into a non-binding license option agreement for olinciguat in 2024 which was terminated in 2025.

Our prior strategy to conduct research and development on sGC stimulators has been discontinued and we do not intend to internally pursue research and development or commercialization with any sGC asset.

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.

We are leveraging our legacy sGC stimulator assets with the goal of generating revenues through potential license agreements, which, if realized, would 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:

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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

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome), cognitive impairment associated with schizophrenia, and Alzheimer's Disease with Vascular Pathology (ADV)

Zagociguat is a CNS-penetrant sGC stimulator that has shown rapid improvements across a range of endpoints reflecting multiple domains of disease activity, including mitochondrial disease-associated biomarkers.

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.

On January 8, 2026, Tisento announced completion of enrollment in PRIZM, a global phase 2b study of Zagociguat for the treatment of MELAS.

Zagociguat received Fast Track designation in June 2025 from the U.S.

Food and Drug Administration for the treatment of MELAS.

CY3018 (CNS-penetrant)

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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.

Praliciguat (peripheral)

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Out-licensed to Akebia in 2021 and renegotiated terms effective December 2024.

In December 2025, Akebia announced that the first patient has been dosed in a Phase 2 clinical trial of praliciguat.

In February 2026, we received a $1,000,000 milestone payment from Akebia tied to the commencement of the

first human clinical trials.

Olinciguat (peripheral)

Cardiovascular diseases

Olinciguat is a vascular sGC stimulator

Cyclerion entered into an exclusive non-binding license option agreement in July 2024 but terminated it in 2025.

Cyclerion is currently exploring potential license opportunities.

Research and Development Programs

The following table presents the status of sGC stimulator assets that are either licensed or optioned to other entities:

The following table presents the status of sGC stimulator assets that are either licensed or plan to be licensed or optioned to other entities:

Akebia License Agreement

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Pursuant to the Akebia License Agreement, Akebia will be responsible for all future research, development, regulatory, and commercialization activities for the out-licensed praliciguat products.

In 2021, Akebia paid a $3.0 million upfront payment to us upon signing of the Akebia License Agreement.

On December 13, 2024, we announced that Cyclerion and Akebia re-negotiated a mutually beneficial amendment to Akebia's exclusive license agreement for praliciguat, a systemic sGC stimulator.

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In addition, Akebia is responsible for all intellectual property expenses associated with praliciguat at an earlier date than as originally agreed between the parties.

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.

On December 1, 2025, Akebia publicly announced that it has recently initiated Phase 2 clinical trials for the treatment of focal segmental glomerulosclerosis (“FSGS”) using Praliciguat.

Pursuant to the terms of amendment, upon initiation (defined as first patient dosed) of a Phase 2 clinical trial in the U.S.

for a product, a $1.0 million development milestone payment would be due to us and this payment was received in February 2026.

We are eligible to receive additional milestone cash payments of up to approximately $557.5 million in total related to potential future development, regulatory, and commercialization milestone payments for praliciguat.

In exchange for a reduction in certain development milestone payments, we are eligible to receive certain higher-tiered sales-based royalties ranging from mid-single-digits to twenty percent.

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.

Unless earlier terminated, the Akebia License Agreement will expire on a product-by-product and country-by-country basis upon the expiration of the last royalty term, which ends upon the longest of (i) the expiration of the patents licensed under the Akebia License Agreement, (ii) the expiration of regulatory exclusivity for such product, and (iii) 10 years from first commercial sale of such product.

Akebia may terminate the Akebia License Agreement in its entirety or only with respect to a particular licensed compound or product upon 180 days’ prior written notice to Cyclerion, subject to certain obligations to license back to Cyclerion licensed compounds and candidates and related assets.

Akebia may terminate the Akebia License Agreement in its entirety or only with respect to a particular licensed compound or product upon 180 days’ prior written notice to

Cyclerion, subject to certain obligations to license back to Cyclerion licensed compounds and candidates and related assets.

The parties also have customary termination rights, subject to a cure period, in the event of the other party’s material breach of the Akebia License Agreement or in the event of certain additional circumstances.

Olinciguat Option to License with CVCO Therapeutics, Inc.

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.

In January 2026, Akebia announced that the first patient was dosed in a Phase 2 clinical trial evaluating praliciguat for focal segmental glomerulosclerosis (FSGS), a rare kidney disease.

The randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of praliciguat, an oral soluble guanylate cyclase (sGC) stimulator, in approximately 60 adult patients.

Cyclerion is not responsible for the conduct of this study, and there can be no assurance regarding the timing, outcome, or potential commercialization of praliciguat.

Tisento Asset Purchase Agreement

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(“Tisento Parent”) and Tisento Therapeutics Inc.

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.

Upon the closing in July 2023, following receipt of approval by the Cyclerion stockholders of the transactions contemplated by the Asset Purchase Agreement, we sold to Tisento certain assets (the “Transferred Assets”) and Tisento assumed certain liabilities relating thereto.

Under the terms of the Asset Purchase Agreement, we agreed not to compete with Tisento through July 2028 either alone or directly or indirectly with or through any affiliate or third party, initiate investigational new drug ("IND")-enabling preclinical development, develop, commercially manufacture, commercialize, or otherwise exploit any compound or product that is (A) a CNS-penetrant sGC stimulator, (B) developed for the treatment of a program indication, and (C) reasonably expected to compete with any compound or product in a purchased program for the treatment of a program indication (any such compound or product, a “Cyclerion Competing Product”) anywhere in the world, or (ii) license, convey, grant, or otherwise transfer any rights to any third party to initiate IND-enabling preclinical development, develop, commercially manufacture, commercialize, or otherwise exploit a Cyclerion Competing Product anywhere in the world.

On January 27, 2025, Tisento Therapeutics announced that the first patient has been dosed in its global Phase 2b PRIZM study.

On January 27, 2025, Tisento Therapeutics announced that the first patient had been dosed in its global Phase 2b PRIZM study.

The study is investigating the impact of once-daily oral zagociguat treatment on fatigue, cognitive impairment, and other key aspects of the rare mitochondrial disease MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes).

In June 2025, Tisento announced that it had received from the U.S, FDA “Fast Track Designation” for MELAS, lactic acidosis and certain Stroke-like Episodes.

PRIZM – a P hase 2b R andomized, Placebo-Controlled Trial I nvestigating Z agociguat in M ELAS – is evaluating the efficacy and safety of oral zagociguat 15 mg or 30 mg compared to placebo when administered once-daily for 12 weeks in participants with genetically and phenotypically defined MELAS.

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PRIZM is a global study that will enroll approximately 44 participants at mitochondrial disease centers of excellence in the U.S., Italy, Germany, United Kingdom, Australia, and Canada.

ClinicalTrials.gov (NCT06402123) for more information.

See ClinicalTrials.gov (NCT06402123) for more information.

In January 2026, Tisento announced completion of enrollment in the global Phase 2b PRIZM clinical trial evaluating oral zagociguat for the treatment of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

The study enrolled approximately 43 participants, and Tisento has indicated that top-line results are expected in the fourth quarter of 2026.

Cyclerion does not control the conduct of this study and cannot provide assurance regarding its outcome or timing.

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 had 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 and subsequent fees totaling $80,000 to extend the term of the Option Agreement.

The Optionee originally could exercise the Option on or before March 20, 2025, which option period was ultimately extended through August 22, 2025.

Thereafter, the parties had an additional 60 days to negotiate the terms of a definitive license agreement.

The parties were unable to agree upon the terms of a license agreement and we were provided notice on October 23, 2025 that the Optionee was terminating the Option Agreement.

We are currently exploring potential license opportunities for olinciguat.

Intellectual Property

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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 158 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.

For our TRD strategy, we have licensed a patent application from MIT.

We also hold an option to license certain technology owned by Medsteer, a leading technology provider of closed loop anesthesia delivery systems, under the Collaboration Agreement.

The patent application licensed from MIT has not yet been granted.

We intend to apply for certain U.S.

and foreign patents related to our TRD product strategy.

The technology underlying our sGC patents and pending patent applications has been developed by us and was not acquired from any in-licensing agreement.

We own all of the issued patents and pending applications.

The intellectual property portfolios for our most advanced product candidates (praliciguat and olinciguat) are summarized below.

The intellectual property portfolios for our most advanced product candidates in the sGC space (praliciguat and olinciguat) are summarized below.

Praliciguat Patent Portfolio

Our praliciguat patent portfolio includes 14 U.S.

issued patents, seven pending U.S.

issued patents, 9 pending U.S.

patent applications, and numerous patents and pending patent applications in foreign jurisdiction.

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Three other U.S.

patents, US 8,748,442, US 9,139,564, and 10,189,809, expire in 2031, and provide generic coverage of praliciguat and intermediates used in the preparation of praliciguat, as well as compounds related to praliciguat, respectively.

patents, US 8,748,442, US 9,139,564, and 10,189,809, expire in 2031, and provide

generic coverage of praliciguat and intermediates used in the preparation of praliciguat, as well as compounds related to praliciguat, respectively.

patent, US 10,183,021 will expire in 2034 and is directed to the treatment of resistant hypertension with praliciguat or combinations of praliciguat and known anti-hypertensives.

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The eighth U.S.

Patent, US 11,389,449, is directed to the treatment of metabolic

syndrome with praliciguat and will expire in 2038.

Patent, US 11,389,449, is directed to the treatment of metabolic syndrome with praliciguat and will expire in 2038.

The ninth U.S.

Patent, US 11,357,777, is directed to the treatment of a severe form of liver disease named n onalcoholic steatohepatitis (NASH) with praliciguat and other compounds and will expire in 2039.

The tenth to thirteenth, U.S.

Patents, US 11,319,308 (expiring in 2039), US 11,773,089 (expiring in 2037), US 11,274,096 (expiring in 2039) and US 11,708,361 (expiring in 2039) are directed to the syntheses of praliciguat or of intermediates useful in the manufacture of praliciguat.

Patent, US 11,357,777, is directed to the treatment of a severe form of liver disease named nonalcoholic steatohepatitis (NASH) with praliciguat and other compounds and will expire in 2039.

The tenth to fourteenth U.S.

Patents, US 11,319,308 (expiring in 2039), US 11,773,089 (expiring in 2037), US 11,274,096 (expiring in 2039), US 11,708,361 (expiring in 2039) and US 12,275,724 (expiring in 2039) are directed to the syntheses of praliciguat or of intermediates useful in the manufacture of praliciguat.

Two pending U.S.

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pending applications is directed to methods of treating diabetic nephropathy with praliciguat, and if issued, will expire in 2040 or later.

Another of the U.S.

pending applications is directed to the use of certain sGC stimulators, including praliciguat for the treatment of HFpEF in post-menopausal women and, if issued, will expire in 2042.

Furthermore, we have eight granted European patents expiring between 2031 and 2039.

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The eighth issued patent, US 11,207,323, will expire in 2034 and provides coverage for stereoisomers of olinciguat.

Five more U.S.

issued patents, US 11,319,308 (expiring in 2039), US 11,773,089 (expiring in 2037), US 11,274,096 (expiring in 2039), US 11,834,444 (expiring in 2038) and US 12,030,874 (expiring in 2039) are directed to the chiral syntheses of olinciguat or the syntheses of intermediates useful in the manufacture of olinciguat.

Seven more U.S.

issued patents, US 11,319,308 (expiring in 2039), US 11,773,089 (expiring in 2037), US 11,274,096 (expiring in 2039), US 11,834,444 (expiring in 2038), US 12,030,874 (expiring in 2039), US 12,247,025 (expiring in 2037 ), and US 12,275, 724 (expiring in 2039) are directed to the chiral syntheses of olinciguat or the syntheses of intermediates useful in the manufacture of olinciguat.

The last U.S.

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patent application, if issued, will expire in 2037 and provides additional coverage for polymorphs of olinciguat.

Another pending U.S.

patent application, if issued, will expire in 2031, and provides generic coverage for olinciguat.

Two pending U.S.

patent applications are directed to processes and synthetic intermediates for preparing olinciguat and, will expire in 2039 and 2037, respectively.

These third and fourth patent applications have recently been allowed.

patent applications, if issued, will expire in 2031 and 2034, respectively, and provides generic coverage for olinciguat.

One pending U.S.

patent application is directed to processes and synthetic intermediates for preparing olinciguat and, will expire in 2037.

A fifth pending U.S.

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Furthermore, we have nine granted European patents expiring between 2031 and 2039 each of them validated in multiple countries or registered in multiple countries as Unitary European Patents;

eight granted Japanese patents expiring between 2031 and 2039;

eight granted Japanese patents

expiring between 2031 and 2039;

seven granted Chinese patents expiring between 2031 and 2039;

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The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and regulations requires the expenditure of substantial time and financial resources.

Failure to comply with the applicable U.S.

requirements at any time during the product development process, approval process or after approval may subject an applicant and/or sponsor to a variety of administrative or judicial sanctions, including imposition of a clinical hold, refusal by the FDA to approve applications, withdrawal of an approval, import/export delays, issuance of warning letters and other types of enforcement letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution,

disgorgement of profits, debarment, or civil or criminal investigations and penalties brought by the FDA, the Department of Justice, State Attorneys General, or other governmental entities.

comply with the applicable U.S.

The process required by the FDA before a drug may be approved and marketed in the United States generally involves the following:

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It is well known that the majority of these treatments have serious limitations despite their benefit.

Many companies have developed or are seeking to develop new treatments for TRD.

Leading companies in TRD market include Janssen (Johnson & Johnson) with Spravato, alongside major pharmaceutical firms Eli Lilly, AbbVie, Pfizer, and Novartis.

Specialized biotechs like Compass Pathways and Axsome Therapeutics are actively developing novel therapies, including psychedelic compounds and rapid-acting agents.

• Pharmacotherapies :

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Only two pharmacotherapies are approved for TRD in the U.S.:

Spravato (esketamine), marketed by Janssen, and Symbyax (olanzapine/fluoxetine hydrochloride capsules), developed by Eli Lilly and Company.

Spravato (esketamine), marketed by Janssen (a subsidiary of Johnson & Johnson) and Symbyax (olanzapine/fluoxetine hydrochloride capsules), developed by Eli Lilly and Company.

• Somatic Therapies :

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The biopharmaceutical industry is highly competitive within and across therapeutic categories and indications.

There are many public and private biopharmaceutical companies, universities, government agencies and other research organizations actively engaged in the research and development and commercialization of products that may be similar to our product candidates or address similar markets.

may be similar to our product candidates or address similar markets.

In addition, the number of companies seeking to develop and commercialize products and therapies competing with our product candidates is likely to increase.

However, we seek to build our portfolio with key differentiating attributes to provide a competitive advantage in the markets we target.

The success of all of our product candidates, if approved, will likely depend upon their efficacy,

safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

The success of all of our product candidates, if approved, will likely depend upon their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

Many of our competitors may have greater financial resources and broader expertise in research and development, manufacturing, nonclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved medicines than we do.

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• There is substantial doubt regarding our ability to continue as a going concern.

We will need to raise additional funding, which may not be available on acceptable terms, if at all, to continue as a going concern and advance our current and any potential future product candidates.

Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations.

We will need to raise additional funding in the near-term, which may not be available on acceptable terms, if at all, to continue as a going concern and advance our current and any potential future product candidates.

Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or our operations altogether.

Raising additional capital may dilute our existing shareholders, restrict our operations or cause us to relinquish valuable rights.

• We are in the process of in-licensing a product candidate for treatment resistant depression and our approach to the discovery and development of this and any future product candidates we may develop may never lead to marketable products.

• We have in-licensed a product candidate for treatment resistant depression and our approach to the discovery and development of this and any future product candidates we may develop may never lead to marketable products.

Risks Related to Development and Clinical Testing of Our Products and Product Candidates

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• We could encounter difficulties in enrolling participants in any future clinical studies, which could delay or prevent progress of our product candidates.

• We may be unable to obtain regulatory approval f and unable to generate product revenue for any product candidate.

• Any future product candidates may cause side effects that may result in label restrictions.

• We may be unable to obtain regulatory approval of clinical trials and product approval and unable to generate product revenue for any product candidate.

• Any of our current or future product candidates may cause side effects that may result in label restrictions.

• We may have to change our nonclinical or clinical study protocols due to regulatory reasons or unanticipated events, which could result in increased costs to us and could delay our development timeline.

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• There are risks in our investment in Tisento tied to Tisento developing, obtaining regulatory approval for, launching and commercializing its product candidates.

• There is uncertainty as to any liquidity or monetizable value of our equity interest in Tisento, which faces all the risks of an early-stage pharmaceutical development company.

• There is uncertainty as to any liquidity or monetizable value of our equity interest in Tisento, a privately-held company, which faces all the risks of an early-stage pharmaceutical development company.

• Akebia may not be successful in developing and commercializing any therapies through its praliciguat out-license with the Company.

• We may not be successful in entering into necessary licenses or collaboration agreements and we may enter into collaboration or license arrangements in the future that ultimately are not successful.

• We may not be successful in entering into necessary licenses or collaboration agreements and maintaining such licenses, and we may enter into collaboration or license arrangements in the future that ultimately are not successful.

• We expect that we will continue to rely on third parties to conduct nonclinical and clinical studies and to manufacture drug supplies for our product candidates.

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• We share confidential information with third-party vendors, including trade secrets and know-how, which increases the possibility that our confidential information will be misappropriated or disclosed.

• We may be unable to adequately protect our proprietary technologies or obtain and maintain issued patents that are sufficient to protect our product candidates.

• We may be unable to adequately protect our proprietary and licensed technologies or obtain and maintain issued patents that are sufficient to protect our product candidates.

• We may infringe the intellectual property rights of others, which may prevent or delay our product development efforts.

• Third parties may infringe our intellectual property rights.

• We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.

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• Our competitors may achieve regulatory approval before us or develop therapies that are safer, more advanced or more effective than ours.

• The impact of healthcare reform and other governmental and private payor initiatives, as well as the potential for reductions in federal government funding for development and clinical trials may harm our business.

• Our prospects for success depend on our ability to attract, retain and motivate qualified personnel.

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• We could fail to maintain proper and effective internal controls and our ability to produce accurate and timely financial statements could be impaired.

• If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse impacts resulting from such compromise, including, but not

limited to, regulatory investigations or actions;

fines and penalties;

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Foreign Corrupt Practices Act, or the FCPA, and other worldwide anti-bribery laws.

• The pandemic and future pandemics may disrupt our business, including our development activities.

Risks Related to the holders of Our Common Stock

• We have limited trading history and a relatively limited public float for our shares and our common stock market price may fluctuate widely.

• We have a relatively limited public float for our shares and our common stock market price may fluctuate widely.

• The market price of our common stock may fluctuate widely and you could lose all or part of your investment in our common stock as a result.

• Any future failure to comply with Nasdaq’s continued listing requirements could result in the delisting of our common stock.

• Any future failure to comply with Nasdaq’s current and proposed continued listing requirements could result in the delisting of our common stock.

• We have adopted anti-takeover provisions in our articles of organization and bylaws and are subject to provisions of Massachusetts law that may frustrate any attempt to remove or replace our current board of directors or to effect a change of control or other business combination involving our company.

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We are a biopharmaceutical company that was incorporated in 2018.

Our business was conducted within Ironwood prior to that time, and we had no history as an independent company prior to the completion of the separation which occurred in 2019.

Our business was conducted within Ironwood Pharmaceuticals, Inc.

prior to that time, and we had no history as an independent company prior to the completion of the separation which occurred in 2019.

We are seeking to develop new products for treatment resistant depression.

We have also developed a pipeline of sGC stimulators, but we have no products approved for commercial sale, and we have never generated revenue from product sales nor have Tisento or Akebia ever generated product sales from products incorporating our compounds.

Our operating activities to date have been limited primarily to organizing and staffing our company, business planning, raising capital, developing our technology, identifying potential product candidates, pursuing partnership opportunities, and conducting early-stage clinical trials for our product candidates.

Our operating activities to date have been limited primarily to organizing and staffing our company, business planning, raising capital, developing our technology, identifying potential product candidates, pursuing partnership opportunities and obtaining licenses we deem necessary for our treatment resistant depression candidate, and conducting early-stage clinical trials for our product candidates.

To date, we have not obtained marketing approval for any of our product candidates;

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Our net losses for the years ended December 31, 2025 and 2024 were $3.5 million and $3.1 million, respectively.

We expect to incur significant losses for at least the next several years, as we continue our research activities and conduct development of, and seek regulatory approvals for, our product candidates.

We expect to incur significant losses for at least the next several years, and for these losses to significantly increase, as we continue our research activities and conduct development of, and seek regulatory approvals for, our product candidates.

Our ability to generate revenue from our current and any potential future product candidates and achieve profitability depends on our ability, alone or with strategic partners, to complete the development of, and obtain the necessary regulatory and essential pricing and reimbursement approvals to commercialize, our product candidates.

We do not know when, if ever, we will generate revenues from sales of our product candidates.

Our expenses could increase beyond expectations if we are required by the FDA, the EMA, or other regulatory agencies, domestic or foreign, to perform clinical and other studies in addition to those that we currently anticipate.

Our expenses would increase beyond expectations if we are required by the FDA, the EMA, or other regulatory agencies, domestic or foreign, to perform clinical and other studies in addition to those that we currently anticipate.

Even if one or more of the product candidates that we develop is approved for commercial sale, we may never generate revenue in amounts sufficient to achieve and maintain profitability.

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We will need to raise additional funding in the near term, which may not be available on acceptable terms, if at all to continue as a going concern and advance our product candidates.

Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations.

Raising additional capital may dilute our existing shareholders, restrict our operations or cause us to relinquish valuable rights.

Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or operations altogether.

Raising additional capital would dilute our existing shareholders, restrict our operations or cause us to relinquish valuable rights.

There is substantial doubt regarding our ability to continue as a going concern.

As of December 31, 2025, we had unrestricted cash and cash equivalents of approximately $3.2 million.

Our management believes that such cash and cash equivalents will not be sufficient to fund our operating expenses and capital requirements beyond the second quarter, whether or not we curtail efforts with respect to certain of our current and future product candidates.

Our management believes that such cash and cash equivalents will not be sufficient to fund our operating expenses and capital requirements through mid-2026, whether or not we curtail efforts with respect to certain of our current and future product candidates.

We will require significant additional funding to advance any of our product candidates beyond the short term and to sustain our operations.

In the event that we are unable to raise the capital necessary, we may need to curtail our operations or cease operations altogether.

Because there is substantial doubt about our ability to continue as a going concern for a reasonable period of time, an investment in our common stock is highly speculative and holders of our common stock could suffer a total loss of their investment.

We may also seek to raise such capital through public or private financing of our securities, royalty financing or debt financing.

Raising funds in the current economic environment may be challenging, and such financing may not be available in sufficient amounts or on acceptable terms, if at all.

Raising funds in the current economic environment is, and may in the future, continue to be challenging, and such financing may not be available in sufficient amounts or on acceptable terms, if at all.

The terms of any financing may harm existing shareholders.

The issuance of additional securities, whether equity or debt, or the possibility of such issuance, may cause the market price of our shares to decline.

The sale of additional equity or convertible securities may dilute the ownership of existing shareholders.

The sale of additional equity or convertible securities would dilute the ownership of existing shareholders.

If we sell shares or other equity securities in one or more other transactions, or issue stock, stock options or other securities pursuant to our current equity plans, investors may be materially diluted by such subsequent issuances.

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Failure to do so could have a material adverse effect on our business.

To the extent we raise additional capital by issuing equity securities, our stockholders may experience substantial dilution.

To the extent we raise additional capital by issuing equity securities, our stockholders would likely experience substantial dilution.

We may sell common stock, preferred stock, convertible securities or other equity or convertible securities in one or more transactions that may include voting rights (including the right to vote as a series on particular matters), preferences as to dividends and liquidation, antidilution, and conversion and redemption rights, subject to applicable law, and at prices and in a manner we determine from time to time.

Such issuances and the exercise of any convertible securities will dilute the percentage ownership of our stockholders and may affect the value of our capital stock and could adversely affect the rights of the holders of such stock, thereby reducing the value of such stock.

Moreover, any exercise of convertible securities may adversely affect the terms upon which we will be able to obtain additional equity capital, since the holders of such convertible securities can be expected to exercise them at a time when we would, in all likelihood, not be able to obtain any needed capital on terms more favorable to us than those provided in such convertible securities.

Incurring debt would result in increased fixed payment obligations, and we may agree to restrictive covenants, such as limitations on our ability to incur additional debt or limitations on our ability to acquire, sell or license intellectual property rights that could impede our ability to conduct our business.

Moreover, any exercise of convertible securities may adversely affect the terms upon which we will be able to obtain additional equity capital, since the holders of such convertible

securities can be expected to exercise them at a time when we would, in all likelihood, not be able to obtain any needed capital on terms more favorable to us than those provided in such convertible securities.

Incurring debt, if available, would result in increased fixed payment obligations, and we may agree to restrictive covenants, such as limitations on our ability to incur additional debt or limitations on our ability to acquire, sell or license intellectual property rights that could impede our ability to conduct our business.

In the event we are unable to raise financing, we may need to reduce or cease operations.

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Research and development of biopharmaceutical products is inherently risky.

We may encounter substantial delays in our activities, including our clinical studies, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities in the development of products to treat patients with serious diseases.

Our business depends heavily on the successful development, clinical testing, regulatory approvals and commercialization of olinciguat (optioned to CVCO) and praliciguat (out-licensed to Akebia), and any future potential product candidates we may acquire or license as well as both the Transferred Assets product candidates we have sold to Tisento.

We may encounter substantial delays in our activities, including our planned clinical studies, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities in the development of products to treat patients with serious diseases.

Our business depends heavily on the successful development, clinical testing, regulatory approvals and commercialization of our lead product candidate for treatment resistant depression, praliciguat (out-licensed to Akebia), any potential future out-licensing of olinciguat, and any future potential product candidates we may acquire or license as well as both the Transferred Assets product candidates we have sold to Tisento.

Any of our current or potential product candidates will require regulatory approval.

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Product candidates in later stages of clinical studies often fail to demonstrate adequate safety and efficacy despite promising nonclinical testing and early clinical studies.

Companies in the biopharmaceutical industry often suffer significant setbacks in later-stage clinical studies;

most product candidates that begin clinical studies are never approved for commercialization by regulatory authorities.

Companies in the biopharmaceutical industry often suffer significant setbacks in both early and later-stage clinical studies as most product candidates that begin clinical studies are never approved for commercialization by regulatory authorities.

Favorable results in earlier stage trials may not be replicated in later stage trials.

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The number of participants required to power the statistical analysis of the study’s endpoints may be very large leading to an extended enrollment period.

Issues such as the proximity of participants to a study site, the complexity of the study design, the ability to recruit investigators with appropriate skill and experience, competing clinical studies for similar therapies or targeting similar participants, perceptions of the benefit-risk profile of the product candidate relative to other available therapies or product candidates, and ability to obtain and maintain institutional review board, or IRB, or ethics committee, or EC, approvals

and participant consents all could have a substantial impact on the timing of clinical trial enrollment.

If sufficient participants cannot be enrolled in clinical studies in a timely way, obtaining study results would be delayed, which may harm our business, prospects, financial condition and results of operations.

The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable.

If we, Akebia and any other future licensees, as applicable, are ultimately unable to obtain regulatory approval for the product candidates, we will be unable to generate product revenue and our business will be substantially harmed.

If we, Tisento, Akebia and any other future licensees, as applicable, are ultimately unable to obtain regulatory approval for the product candidates, we will be unable to generate product revenue and our business will be substantially harmed.

A product candidate cannot be commercialized until the appropriate regulatory authorities have reviewed and approved the product candidate.

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• negative results from ongoing studies or other industry studies involving product candidates modulating the same or similar mechanism of action;

• delays in reaching or failing to reach agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical study sites, the terms of which can be subject to considerable negotiation and may vary significantly among different CROs and study sites;

• delays in reaching or failing to reach agreement on acceptable terms with prospective contract research organizations, or contract research organizations (“CRO”), and clinical study sites, the terms of which can be subject to considerable negotiation and may vary significantly among different CROs and study sites;

• inadequate quantity or quality of a product candidate or other materials necessary to conduct clinical studies, for example delays in the manufacturing of sufficient supply of finished drug product;

• difficulties obtaining EC or IRB approval(s) to conduct a clinical study at a prospective site or sites;

• challenges in recruiting and enrolling participants in clinical studies, the proximity of participants to study sites, eligibility criteria for the clinical study, the nature of the clinical study protocol, the availability of approved effective treatments for the relevant disease and competition from other clinical study programs for similar indications;

availability of approved effective treatments for the relevant disease and competition from other clinical study programs for similar indications;

• severe or unexpected drug-related side effects experienced by participants in a clinical study;

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Changes in regulatory requirements, FDA guidance or unanticipated events during nonclinical studies and clinical studies may force amendment to nonclinical studies and clinical study protocols or the FDA may impose additional nonclinical studies and clinical study requirements.

Amendments or changes to clinical study protocols would require resubmission to the FDA and IRBs for review and approval, which may increase the cost or delay the timing or successful completion of clinical studies.

Amendments or changes to clinical study protocols would require resubmission to the FDA and IRBs for review and approval, which may increase the cost or delay the

timing or successful completion of clinical studies.

Similarly, amendments to nonclinical studies may increase the cost or delay the timing or successful completion of those nonclinical studies.

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Obtaining and maintaining regulatory approval of product candidates in one jurisdiction does not guarantee that obtaining or maintaining regulatory approval in any other jurisdiction will be possible, but a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.

For example, even if the FDA or other comparable foreign regulatory authority grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing and promotion of the product candidate in those

Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional nonclinical or clinical studies, as studies conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions.

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There are other types of data/market exclusivity rights granted after approval that may not confer exclusivity anticipated if the competitive landscape changes and our business, prospects, financial condition and results of operations could be materially harmed.

Future pandemics may disrupt our business, including our development activities.

Many nations, including the United States, continue to implement mitigation measures that have in the past and may in the future limit our ability to access patients and physicians at certain local clinical centers that are participating in any future development activities.

We may face limitations and difficulties enrolling patients in our planned and future clinical trials if the patient populations that are eligible for our clinical trials are affected by the coronavirus and/or the COVID-19 vaccines or other pandemics.

Any such restrictions at trial sites could delay any future clinical studies.

In addition, if the patients enrolled in any future clinical trials become infected with COVID-19 or other viruses, we may have more adverse events and deaths in our clinical trials as a result.

Vulnerable patients may be at a higher risk of contracting COVID-19 and other viruses may experience more severe symptoms from the disease, adversely affecting our chances for regulatory approval or requiring further clinical studies.

The adverse effects that may occur from administration of vaccines to patients participating in our future clinical trials could adversely affect clinical trial outcomes or data analysis.

Furthermore, the extent to which the COVID-19 pandemic, or future outbreaks of infectious disease, hinders access to facilities, procurement of resources, raw materials or components necessary for research studies or preclinical or clinical development is not fully predictable.

Delays and disruptions from the COVID-19 pandemic, or future outbreaks of infectious disease, may increase our capital needs while potentially interfering with our access to capital.

Risks Related to Reliance on Licensees, Tisento and Other Third Parties

We may not succeed in our pursuit of capital, capabilities, and transactions for the development and commercialization of our future clinical stage assets, which would affect our financial condition.

We are seeking capital, capabilities, and transactions to advance the development of product candidates we may acquire rights to in the future.

There can be no assurance that this process will result in any effective negotiations toward, reaching terms of, executing agreements relating to, or completing any transaction or that any such transaction

will be successful.

Failure to complete any of the foregoing efforts would materially adversely affect our business, prospects, financial condition and results of operations.

We are seeking capital, capabilities, and transactions to advance the development of our product candidate for treatment resistant depression and other product candidates we may acquire rights to in the future.

Failure to complete any of the

foregoing efforts would materially adversely affect our business, prospects, financial condition and results of operations.

Akebia may not be successful in developing any therapies through the praliciguat out-license and we may not realize any future revenue from the out-license.

On June 3, 2021, we entered into a license agreement with Akebia 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 praliciguat and other related products and forms thereof enumerated in such agreement.

On June 3, 2021, we entered into 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 praliciguat and other related products and forms thereof enumerated in such agreement.

Under the agreement, Akebia is responsible for all research, development, regulatory, and commercialization activities for certain products.

On December 13, 2024, we and Akebia entered into Amendment #1 to License Agreement (the “2024 Amendment”) to the original 2021 license agreement.

Under the terms of the 2024 Amendment, Akebia paid the Company (i) $1.25 million in December 2024 and has agreed to pay an additional $0.5 million on or before September 30, 2025.

On December 13, 2024, we and Akebia entered into Amendment #1 to License Agreement (the “2024 Amendment”) to the original Akebia License Agreement.

Under the terms of the 2024 Amendment, Akebia paid the Company (i) $1.25 million in December 2024 and an additional $0.5 million in September 2025.

In addition, Akebia has agreed to assume control of the preparation, filing, prosecution and maintenance of certain Cyclerion patents, and the expenses associated therewith, at an earlier date than as originally agreed between the parties.

The parties have agreed to the reduction of certain development milestones and the increase of certain royalty rates on net sales and sublicense income.

Pursuant to the terms of the 2021 License Agreement, as amended, Akebia will pay Cyclerion tiered royalties ranging from mid-single digit to twenty percent of net sales.

Pursuant to the terms of the Akebia License Agreement, as amended, Akebia will pay Cyclerion tiered royalties ranging from mid-single digit to twenty percent of net sales.

Cyclerion’s obligations to deliver certain drug products have also ceased.

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While we believe that Tisento’s technology, development experience and scientific knowledge provide it with competitive advantages, it may face potential competition from many different sources, including large pharmaceutical and biotechnology companies, academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for the research, development, manufacturing and commercialization of similar products.

Any investigational products that we successfully develop and commercialize will compete with new immunotherapies that may become available in the future.

Any investigational products that Tisento may successfully develop and commercialize will compete with new immunotherapies that may become available in the future.

As a result, our investment in Tisento is risky and our equity interest in Tisento could be significantly diluted in the future if Tisento seeks to raise additional capital or is unable to raise additional capital on favorable terms, if at all.

If Tisento suffers adverse effects, it may not be able to continue as a going business concern, and we may lose our entire investment.

Tisento is a privately-held company and there is no public market for its securities.

As a result, it may be difficult to sell any of our securities position in Tisento in the near term, if at all.

We lack operational control over Tisento.

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• a partner’s sales and marketing activities or other operations may not be in compliance with applicable laws resulting in civil or criminal proceedings.

We expect in the future to rely on third parties to conduct any nonclinical or clinical studies for any potential future product candidates.

We expect in the future to rely on third parties to conduct any nonclinical or clinical studies for any existing or potential future product candidates.

If these third parties do not successfully carry out their contractual duties or meet expected deadlines, necessary regulatory approvals for or commercialization of any potential future product candidates may not be obtainable and our business could be substantially harmed.

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Risks Related to Our Intellectual Property Rights

If we or our licensees or Tisento are unable to adequately protect proprietary technologies, or obtain and maintain issued patents that are sufficient to protect their respective product candidates, others could compete against us, our licensees and Tisento more directly, which would have a material adverse impact on our business, prospects, financial condition and results of operations.

Our success will depend in part on our and our licensees and Tisento’s ability to obtain and maintain patent and other proprietary protection in the United States and other countries for commercially important technology, inventions and know-how related to our business, defend and enforce patents, should they issue, preserve the confidentiality of trade secrets and operate without infringing the valid and enforceable patents and proprietary rights of third parties.

If we or our licensors, licensees or Tisento are unable to adequately protect proprietary technologies, or obtain and maintain issued patents that are sufficient to protect their respective product candidates, others could compete against us, our licensees and Tisento more directly, which would have a material adverse impact on our business, prospects, financial condition and results of operations.

Our success will depend in part on our licensors, licensees and Tisento’s ability to obtain and maintain patent and other proprietary protection in the United States and other countries for commercially important technology, inventions and know-how related to our business, defend and enforce patents, should they issue, preserve the confidentiality of trade secrets and operate without infringing the valid and enforceable patents and proprietary rights of third parties.

We strive to protect and enhance the proprietary technologies that we believe are important to our business, including seeking patents intended to cover our product candidates and compositions, their methods of use and any other Inventions that are important to the development of our business.

We have 22 issued U.S.

patents, eleven pending U.S.

patents, 12 pending U.S.

patents applications and numerous foreign patents and pending patent applications.

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We also rely on patents issued to licensors providing patent licenses for our treatment resistant depression candidate.

See “Business — Intellectual Property.” We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

The patent positions of biotechnology and pharmaceutical companies, including ours, involve complex legal and factual questions, which in recent years have been the subject of much litigation, and, therefore, the issuance, scope, validity, enforceability and commercial value of any patent claims that we may obtain cannot be predicted with certainty.

Patent applications may not be granted as issued patents in any particular jurisdiction and, even if they do,

these patents may not include claims with a sufficient scope to protect our product candidates or otherwise provide any competitive advantage.

Patent applications may not be granted as issued patents in any particular jurisdiction and, even if they do, these patents may not include claims with a sufficient scope to protect our product candidates or otherwise provide any competitive advantage.

Even if patent applications are issued, competitors and other third parties may infringe, misappropriate or otherwise violate patents and other intellectual property rights.

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Our success will depend in part on our ability to operate without infringing, misappropriating or otherwise violating the intellectual property and proprietary rights of third parties.

Other parties may allege that our product candidates or the use of our technologies infringes or otherwise violates patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization.

Other parties may allege that our product candidates or the use of our technologies or technologies licensed by us infringe or otherwise violate patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization.

There may be third-party patents or patent applications with claims to compositions, materials, formulations, methods of manufacture or methods for treatment related to our product candidates.

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Any of these risks coming to fruition could have a material adverse effect on our business, prospects, financial condition and results of operations.

We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.

Our employee, consultants, non-academic outside scientific collaborators and other advisors enter into confidentiality and intellectual property assignment agreements with us or have entered into confidentiality and intellectual property assignment agreements with Ironwood.

We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property we own or license from third parties.

We seek to have inventions assigned to us by the parties rendering services whenever possible.

However, we may not be able to enter into these agreements with all parties (for

example with academic collaborators) or these agreements may not be honored and may not effectively assign intellectual property rights to us.

Our in-bound licenses seek

to insure that all of the intellectual property licensed to us is owned by the licensor.

However, we may not be able to enter into these agreements with all parties (for example with academic collaborators) or these agreements may not be honored and may not effectively assign intellectual property rights to us.

Litigation may be necessary to defend against these and other claims challenging inventorship or ownership.

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Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies and patent protection could be reduced or eliminated for non-compliance with these requirements.

The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions over the lifetime of owned patents and applications For in-bound licensed intellectual property rights, failure to maintain compliance with such requirements would adversely impact our rights as regards those patents and applications.

In some cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules.

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Obtaining and enforcing patents in the biotechnology industry involves both technological and legal complexity, and is therefore costly, time-consuming and inherently uncertain.

In addition, the United States has recently enacted and is currently implementing wide-ranging patent reform legislation:

In addition, the United States has enacted and implemented wide-ranging patent reform legislation:

the Leahy-Smith America Invents Act, or the America Invents Act.

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These provisions affect the way patent applications will be prosecuted and may also affect patent litigation.

It is not yet clear what, if any, impact the America Invents Act will have on the operation of our business.

It is not yet clear what, if any, impact the America Invents Act will have on the operation of certain elements of our product candidates.

However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of any patents that may issue from our patent applications, all of which could have a material adverse effect on our business, prospects, financial condition and results of operations.

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We also engage and, in the future, intend to engage advisors and consultants who are concurrently employed at universities or who perform services for other entities.

We may be subject to claims that we or our employees, advisors or consultants have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former

employer or other third party.

We may be subject to claims that we or our employees, advisors or consultants or third parties from whom we license certain technologies have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer or other third party.

We may be subject to claims that an employee, advisor or consultant performed work for us that conflicts with that person's obligations to a third party, such as an employer, and thus, that the third party has an ownership interest in the intellectual property arising out of work performed for us.

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Unfavorable global economic and political conditions could harm our business, prospects, financial condition and results of operations.

Our results of operations could be harmed by general conditions in the global economy and in the global financial markets as well as adverse economic conditions caused by political unrest.

Our results of operations could be harmed by general conditions in the global economy and in the global financial markets as well as adverse economic conditions caused by political unrest or loss of government funding for product candidates.

A severe or prolonged economic downturn and severe political disruption could result in a variety of risks to our business, including weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.

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Any of the foregoing could harm our business, prospects, financial condition and results of operations.

If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse impacts resulting from such compromise, including, but not limited to, regulatory investigations or actions;

If our information technology systems or data, or those of CRO and other third parties upon which we rely, are or were compromised, we could experience adverse impacts resulting from such compromise, including, but not limited to, regulatory investigations or actions;

fines and penalties;

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However, there can be no assurance that the Company will be able to maintain compliance with the Bid Price Requirement, would receive sufficient shareholder support for a reverse stock split, or will otherwise be in compliance with other Nasdaq Listing Rules.

In January 2026, NASDAQ refiled with the SEC an application to allow NASDAQ to delist certain companies from the NASDAQ Capital Market and NASDAQ Global Market where companies with a market value of listed securities below $5 million for 30 consecutive business days face immediate suspension and delisting, without the usual compliance period or automatic stay (the “Proposed Market Value Rule”).

The SEC has requested comments on the proposed application.

The comment period for public comments ended on February 19, 2026, after which time the SEC may elect to accept the NASDAQ proposal.

If approved by the SEC, the rule will become effective within 45 days of publication in the Federal Register, or within up to 90 days if extended by the SEC pursuant to Section 19(b)(2) of the Exchange Act.

Currently, the Company would not meet the requirements of the Proposed Market Value Rule and if the Proposed Market Value Rule is approved, the Company may not meet the requirements under the Proposed Market Value Rule to maintain its current listing on the NASDAQ Capital Market.

The loss of the Company’s listing on the NASDAQ Capital Market would result in the Company’s common stock trading on the OTC Market, which could adversely affect the market price of the Company’s common stock.

The market price of our common stock may fluctuate widely and you could lose all or part of your investment in our common stock as a result.

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• announcement or expectation of additional financing efforts;

• publication of research reports by securities analysts about us or our competitors or our industry and speculation regarding our company or our stock price in the financial or scientific press or in online investor communities;changes in market conditions in the pharmaceutical and biotechnology sector;

• Nasdaq's rules, which impose certain continued listing requirements, including a minimum $1 bid price, such that a failure to meet these requirements would lead Nasdaq to take further steps to delist our common stock;

• changes in market conditions in the pharmaceutical and biotechnology sector;

• Nasdaq's rules, which impose certain continued listing requirements, including a minimum $1 bid price, and the Proposed Market Value Rule, such that a failure to meet these requirements would lead Nasdaq to take further steps to delist our common stock;

• changes in general market and economic conditions.

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These steps have included, among others, selling marketable securities that we might otherwise hold for the long term and deploying our cash in non-investment assets.

We have recently sold marketable securities, including at times at a loss, and we may be forced to sell our investment assets at unattractive prices or to sell assets that we otherwise believe benefit our business in the future to remain below the requisite threshold.

We may be forced to sell our investment assets at unattractive prices or to sell assets that we otherwise believe benefit our business in the future to remain below the requisite threshold.

We may also seek to acquire additional non-investment assets to maintain compliance with the Investment Company Act, and we may need to incur debt, issue additional equity or enter into other financing arrangements that are not otherwise attractive to our business.

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It is uncertain if and to what extent various states will conform to federal tax laws.

In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change U.S.

corporation’s ability to use its pre-change NOL carryforwards and other pre-change U.S.

tax attributes (such as research tax credits) to offset its post-change income or taxes may be limited.

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In addition, at the state level, there may be periods during which the use of NOL carryforwards is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.

As a result, we may be unable to use all or a

material portion of our NOL carryforwards and other tax attributes, which would harm our future operating results by effectively increasing our future tax obligations.

As a result, we may be unable to use all or a material portion of our NOL carryforwards and other tax attributes, which would harm our future operating results by effectively increasing our future tax obligations.

We maintain our cash at financial institutions, often in balances that exceed federally insured limits.

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Our board of directors also may issue shares of any class or series of preferred stock in the future without shareholder approval and upon such terms as our board of directors may determine.

The rights of the holders of our common stock will be subject to, and may be harmed by, the rights of the holders of any class or series of preferred stock that may be issued in the future.

The rights of the holders of our

common stock will be subject to, and may be harmed by, the rights of the holders of any class or series of preferred stock that may be issued in the future.

Massachusetts state law also prohibits us from engaging in specified business combinations unless the combination is approved or consummated in a prescribed manner.

1 unchanged sentence

Our articles of organization designate the state and federal courts located within the Commonwealth of Massachusetts as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our shareholders, which could discourage lawsuits against us and our directors and officers.

creditors or other constituents, any action asserting a claim arising pursuant to any provision of the Massachusetts Business Corporation Act, or the MBCA, or any action asserting a claim governed by the internal affairs doctrine, in all cases subject to the court's having personal jurisdiction over the indispensable parties named as defendants.

Our restated articles of organization designate the state and federal courts located within the Commonwealth of Massachusetts as the sole and exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a claim of breach of a fiduciary duty owed by any of our directors or officers to us or our shareholders, creditors or other constituents, any action asserting a claim arising pursuant to any provision of the Massachusetts Business Corporation Act, or the MBCA, or any action asserting a claim governed by the internal affairs doctrine, in all cases subject to the court's having personal jurisdiction over the indispensable parties named as defendants.

In additional, our articles of organization provide that unless our board of directors consents in writing to the selection of an alternative forum, the U.S.

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Depending on the environment, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example:

incident response plans and procedures, disaster recovery/business continuity plans, risk assessments, implementation of security standards and certifications, encryption of data, network security controls, data segregation, access controls, physical security, asset management, tracking and disposal, systems monitoring, vendor risk management program, employee training and penetration testing.

tracking and disposal, systems monitoring, vendor risk management program, employee training and penetration testing.

Our assessment and management of material risks from cybersecurity threats are integrated into our overall risk management processes.

31 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business