What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-04 compared with 2024-03-05 · 267 added, 217 removed, 1002 unchanged (33% of the section changed)

Cyclerion Therapeutics, Inc.

(“Cyclerion”, the “Company” or “we”) is a biopharmaceutical company on a mission to develop treatments for serious diseases.

Cyclerion became an independent public company on April 1, 2019 after Ironwood Pharmaceuticals, Inc., or Ironwood, completed a tax-free spin-off of its sGC business, which we refer to herein as the “Separation”.

Cyclerion Securities Corporation, a wholly owned subsidiary, was incorporated in Massachusetts on November 15, 2019 and was granted securities corporation status in Massachusetts for the 2019 tax year.

At inception, Cyclerion was a biopharmaceutical company focused on the treatment of serious diseases with novel soluble guanylate cyclase ("sGC") stimulators in both the central nervous system (“CNS”) and the periphery.

The nitric oxide (“NO”) sGC cyclic guanosine monophosphate (“cGMP”) signaling pathway is a fundamental mechanism that precisely controls key aspects of physiology throughout the body.

The NO-sGC-cGMP pathway regulates diverse and critical biological functions in both the CNS and the periphery and has been successfully targeted with several drugs.

On July 28, 2023, the Company sold two of its CNS-penetrant sGC stimulator assets, - zagociguat and CY3018 – (the “Transferred Assets”) to Tisento in exchange for $8.0 million in cash consideration, $2.4 million as reimbursement for certain operating expenses related to the Transferred Assets for the period between signing and closing of the transaction, and 10% of all of Tisento’s parent’s outstanding equity securities at the time of the closing.

See “Tisento Asset Purchase Agreement” below.

Prior to the sale of the Transferred Assets, Cyclerion’s portfolio included novel sGC stimulators that modulate signaling networks in both the CNS and the periphery.

The following table is a high-level summary of Cyclerion’s portfolio assets prior to the sale:

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 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.

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.

The following table is a high-level summary of our historical sGC portfolio:

Indication(s)

Zagociguat (CNS-penetrant)

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.

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.

CY3018 (CNS-penetrant)

Neuropsychiatric

Neuropsychiatric disorders

CY3018 is a CNS-penetrant sGC stimulator in preclinical development that has potential for the treatment of neuropsychiatric diseases and disorders.

Sold to Tisento as part of the Asset Purchase Agreement

Sold to Tisento as part of the Asset Purchase Agreement in July 2023

Olinciguat (peripheral)

Cardiovascular

Olinciguat is a vascular sGC stimulator that the Company

Management plans to seek to out-license olinciguat

intends to out-license for cardiovascular diseases.

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)

Focal Segmental Glomerulosclerosis (FSGS)

Praliciguat is a systemic sGC stimulator that is licensed to Akebia for the treatment of rare kidney disease.

Out-licensed to Akebia

Although all assets that were within Cyclerion’s portfolio were sGC stimulators, the Transferred Assets sold to Tisento are uniquely different from the assets retained by Cyclerion (olinciguat and praliciguat).

The Transferred Assets have high exposure to the CNS (i.e., CNS-penetrant sGC stimulators) and the Cyclerion retained assets are peripheral sGC stimulators.

The retained assets are therefore not interchangeable with the Transferred Assets and do not provide the same benefit in CNS and correspondingly the Transferred Assets do not provide the same potential benefit for systemic/vascular diseases.

Cyclerion assets which have been retained are either currently out-licensed (praliciguat) or management is seeking to out-license (olinciguat).

The Company’s prior strategy to conduct research and development on sGC stimulators for CNS has been discontinued subsequent to the sale of the Transferred Assets.

Cyclerion does not intend to internally pursue research and development or commercialization with any type of sGC assets.

Cyclerion intends to utilize royalties and milestones from olinciguat and praliciguat out-licensing to build a new portfolio and advance the development of those new assets.

Praliciguat is a systemic sGC stimulator that is licensed to Akebia for the treatment of a rare kidney disease.

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

Research and Development Programs

The following table presents the status of our retained sGC stimulator assets:

In addition to activities related to the retained assets, Cyclerion continues to evaluate other activities to enhance shareholder value, which include potentially acquiring new assets which Cyclerion believes may have promise, as well as potential collaborations, licenses, mergers, acquisitions and/or other targeted investments.

Cyclerion GmbH, a wholly owned subsidiary, was incorporated in Zug, Switzerland on May 3, 2019.

The functional currency is the Swiss franc.

The liquidation process for Cyclerion GmbH has been concluded and the subsidiary is pending deregistration from the commercial registry.

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, the Company and Akebia entered into a License Agreement (the “Akebia License Agreement”) relating to the exclusive worldwide license by the Company 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 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.

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.

Akebia paid a $3.0 million up-front payment to the Company upon signing of the Akebia License Agreement and the Company is eligible to receive additional milestone cash payments of up to $585 million in total potential future development, regulatory, and commercialization milestone payments for Praliciguat.

In addition to these cash milestone payments, Akebia will pay the Company tiered royalty payments on net sales in certain major markets at percentages ranging from the mid-single digits to the high-teens, subject to certain reductions and offsets.

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.

Under this new license amendment, we will receive $1.75 million in amendment payments, of which $1.25 million was paid in December 2024 and an additional payment of $0.5 million is due in September 2025.

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.

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.

1 unchanged sentence

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.

Tisento Asset Purchase Agreement

On May 11, 2023, the Company entered into an Asset Purchase Agreement (the “Asset Purchase Agreement”) with an investor group that included Peter Hecht (our former CEO), JW Celtics Investment Corp and JW Cycle Inc.

On May 11, 2023, we entered into an Asset Purchase Agreement (the “Asset Purchase Agreement”) with an investor group that included Peter Hecht (our former CEO), JW Celtics Investment Corp and JW Cycle Inc.

which subsequently changed their names to Tisento Therapeutics Holdings Inc.

(“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, the Company 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 the Company 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.

Under the terms of the Asset Purchase Agreement, Cyclerion has agreed not to compete with Tisento from July 28, 2023 through the July, 2028 either alone or directly or indirectly with or through any affiliate or third party, initiate 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.

Although the Company has shifted its strategy to build a new portfolio of non-sGC stimulator assets within the CNS therapeutic area, our mission remains to advance treatments for serious diseases.

If the Company identifies suitable new assets outside of the sGC stimulator space, the Company will seek to raise funds and build an organization suitable to advance these assets.

The Company’s goal is to find the best combination of capital, capabilities, and transactions that will enable the advancement of current and any future assets the Company may acquire for patients in a way that maximizes shareholder value.

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.

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.

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).

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.

The PRIZM study has a crossover design, with two 12-week treatment periods separated by a 4-week washout period.

All participants will receive zagociguat during one of the 12-week periods and placebo during the other.

Participants who complete the study may be eligible for an open-label extension study.

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.

Intellectual Property

We protect the intellectual property and proprietary technology that we believe is important to our business, including by pursuing and maintaining U.S.

and foreign patents that cover our product candidates and compositions,

their methods of use and the processes for their preparation, as well as any other relevant inventions and improvements that are commercially important to the development of our business.

and foreign patents that cover our product candidates and compositions, their methods of use and the processes for their preparation, as well as any other relevant inventions and improvements that are commercially important to the development of our business.

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.

We expect to also rely on licenses for patented intellectual property owned by third parties.

Our commercial success depends in part on our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions, improvements and know-how related to our business, defend and enforce our patents, preserve the confidentiality of our trade secrets and operate without infringing the valid and enforceable patents and proprietary rights of third parties.

We have nineteen issued U.S.

patents, nine pending U.S.

patents applications and numerous foreign patents and pending patent applications.

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.

5 unchanged sentences

Our praliciguat patent portfolio includes 13 U.S.

issued patents, five pending U.S.

issued patents, seven pending U.S.

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

10 unchanged sentences

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 NASH with praliciguat and other compounds and will expire in 2039.

The tenth to thirteen, 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.

Two pending U.S.

patent applications that, if issued, will expire in 2031 and 2034, respectively, provide generic coverage for praliciguat.

One additional U.S.

patent application that, if issued, will expire in 2037 provides coverage for methods of large-scale preparation of praliciguat.

patent applications that, if issued, will expire in 2031 and 2034, respectively, provide generic coverage for praliciguat composition of matter.

Two additional U.S.

patent applications that, if issued, will expire in 2037 and 2039, respectively, provide coverage for methods of large-scale preparation of praliciguat.

We also have a pending U.S.

application directed to a praliciguat formulation, that, if issued, will expire in 2036.

Another pending U.S.

application is directed to phosphorous prodrugs of praliciguat and, if issued, will expire in 2037.

Another of the U.S.

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

Furthermore, we have eight granted European patents, one expiring in 2031, another one in 2032, a third one in 2034, a fourth one in 2036, a fifth to seventh ones in 2037, and the eighth one in 2039, each of them validated in multiple countries or registered in multiple countries as an European Unitary Patent;

nine granted Japanese patents, one expiring in 2031, another in 2034, two in 2036, four others in 2037 and one in 2039;

seven granted Chinese patents, two expiring in 2031, one in 2032, three in 2034, and one expiring in 2037;

and a large number of

issued patents in foreign jurisdictions expiring between 2031 and 2039.

Some of these patents may be eligible for patent term extension depending on the jurisdiction.

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

Each of these patents is validated in multiple countries or registered in multiple countries as a European Unitary Patent.

We hold nine granted Japanese patents expiring between 2031 and 2040.

We also have numerous patent applications pending in foreign jurisdictions.

Olinciguat Patent Portfolio

Our olinciguat patent portfolio includes thirteen U.S.

Our olinciguat patent portfolio includes 14 U.S.

issued patents, five pending U.S.

6 unchanged sentences

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

The fifth U.S.

patent, US 10,517,874, which will expire in 2034 is directed to the treatment of SCD using olinciguat alone or in combinations with other therapeutic agents.

Two additional U.S.

The sixth and seventh U.S.

issued patents, US 10,889,577, and US 11,572,358, will expire in 2037 and are directed to polymorphs of olinciguat.

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

Four 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), and US 11,834,444 (expiring in 2038 or potentially later) are directed to the chiral syntheses of olinciguat or the syntheses of intermediates useful in the manufacture 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.

The last U.S.

Patent, US 11,357,777, is directed to the treatment of NASH with olinciguat and other compounds and will expire in 2039.

issued patent, US 11,357,777, is directed to the treatment of NASH with olinciguat and other compounds and will expire in 2039.

One pending U.S.

3 unchanged sentences

Two pending U.S.

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

A pending US application is directed to the treatment of heart failure with preserved ejection fraction (HFpEF) in post-menopausal women with olinciguat and other sGC stimulators.

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.

A fifth pending U.S.

patent application is directed to the treatment of heart failure with preserved ejection fraction (HFpEF) in post-menopausal women with olinciguat and other sGC stimulators.

If issued, the corresponding patent will expire in 2042.

Furthermore, we have nine granted European patents, one expiring in 2031, another in 2032, two in 2034, four in 2037, and one in 2039, each of them validated in multiple countries or registered in multiple countries as Unitary European Patents;

eight granted Japanese patents, one expiring in 2031, three others in 2034, three expiring in 2037 and one in 2039;

six granted Chinese patents, two expiring in 2031, another one in 2032, two more in 2034 and one in 2037;

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;

seven granted Chinese patents expiring between 2031 and 2039;

and a large number of issued patents in other foreign jurisdictions, expiring between 2031 and 2039.

3 unchanged sentences

In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application, assuming that all applicable maintenance or annuity fees are paid.

In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the USPTO, in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent.

In the United States, and China, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the respective patent offices, in examining and granting a patent, or, in the US, the term may be shortened if a patent is terminally disclaimed over an earlier-filed patent.

The duration of foreign patents varies in accordance with provisions of applicable local law, but typically is also 20 years from the earliest effective filing date.

1 unchanged sentence

In addition, the term of a U.S.

patent that covers an FDA-approved drug may be eligible for patent term extension under the Drug Price Competition and Hatch-Waxman Act, to account for some of the time the drug is under development and regulatory review after the patent is granted.

patent that covers an US Food and Drug Administration (FDA)-approved drug may be eligible for patent term extension under the Drug Price Competition and Hatch-Waxman Act, to account for some of the time the drug is under development and regulatory review after the patent is granted.

For a drug for which FDA approval is the first permitted marketing of the active ingredient, the Hatch-Waxman Act allows for extension of the term of one U.S.

patent that includes at least one claim covering the composition of matter of an FDA-approved drug (drug substance or drug product), an FDA-approved method of treatment using the drug and/or a method of manufacturing the

FDA-approved drug.

The extended patent term cannot exceed the shorter of five years beyond the non-extended expiration of the patent or 14 years from the date of the FDA approval of the drug.

Some foreign jurisdictions, including Europe and Japan, have similar patent term extension provisions, which allow for extension of the term of a patent that covers a drug approved by the applicable foreign regulatory agency.

Some foreign jurisdictions, including Europe, Japan, and China, have similar patent term extension provisions, which allow for extension of the term of a patent that covers a drug approved by the applicable foreign regulatory agency.

Trade Secrets and Proprietary Information

15 unchanged sentences

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.

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.

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

1 unchanged sentence

• submission to the FDA of an IND application for human clinical testing, which must become effective before human clinical trials may commence;

• approval by an independent IRB to proceed with initiating the clinical trial at each corresponding investigational site.

• approval by an independent institutional review board ("IRB") to proceed with initiating the clinical trial at each corresponding investigational site.

• performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, GCPs and other clinical-trial related regulations to establish the safety and efficacy of the product for each proposed indication;

43 unchanged sentences

On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the manufacturing facilities, FDA will issue either an approval letter or a Complete Response Letter.

An approval letter authorizes commercial marketing of the drug and is accompanied by specific prescribing

information for specific conditions of use.

An approval letter authorizes commercial marketing of the drug and is accompanied by specific prescribing information for specific conditions of use.

A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form.

34 unchanged sentences

rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted.

We are currently not anticipating acquiring any assets for severe pediatric applications.

Post-Approval Requirements

3 unchanged sentences

The FDA may impose a number of post-approval requirements as a condition of approval of an NDA, such as Phase 4 clinical trials or a REMS.

In addition, entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced inspections by the FDA and such state agencies for compliance with current GMP requirements.

and such state agencies for compliance with current GMP requirements.

Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.

31 unchanged sentences

Pediatric Development

In the European Union, companies developing a new medicinal product must agree to a Pediatric Investigation Plan, or PIP, with the EMA and must conduct pediatric clinical trials in accordance with that PIP, unless a deferral or waiver applies, (e.g., because the relevant disease or condition occurs only in adults).

The MAA for the product must include the results of pediatric clinical trials conducted in accordance with the PIP, unless a waiver applies or a deferral has been granted, in which case the pediatric clinical trials must be completed at a later date.

Where the MAA includes the results of all pediatric studies conducted in accordance with the PIP and the results are reflected in the approved summary of product characteristics, the holder of a patent or supplementary protection certificate is entitled to receive a six-month extension of the protection under a supplementary protection certificate or, in the case of orphan medicinal products, the product is eligible for a two-year extension of the orphan

market exclusivity.

In the European Union, companies developing a new medicinal product must agree to a Pediatric Investigation Plan, or PIP, with the European Medicines Agency (EMA) and must conduct pediatric clinical trials in accordance with that PIP, unless a deferral or waiver applies, (e.g., because the relevant disease or condition occurs only in adults).

The MAA for the product must include the results of pediatric clinical trials conducted in accordance

with the PIP, unless a waiver applies or a deferral has been granted, in which case the pediatric clinical trials must be completed at a later date.

This pediatric reward is subject to specific conditions and is not automatically available when data in compliance with the PIP are developed and submitted.

2 unchanged sentences

The Best Pharmaceuticals for Children Act (BPCA) also allows for agreement with FDA on a pediatric written request that, if fulfilled, may extend data exclusivity for the molecule for an additional 6 months.

We are currently not seeking to develop any new drug candidates for severe pediatric applications.

We believe that our plans for a potential new drug candidate for TRD under consideration may be applicable for the treatment of pediatric patients.

Despite our belief that the potential product that we intend to develop and commercialize in TRD will be differentiated, we will face competition from many different sources.

Potential competition includes major/specialty pharmaceutical, biopharmaceutical, device and biotechnology companies, academic institutions, governmental agencies and medical research organizations.

Additionally, we would expect that, if approved, our product will compete with the standard of care and any new therapies that may become available in the future.

Several biopharmaceutical companies have therapies in clinical development for TRD and we are aware that many more are investigating treatments for TRD (e.g., psychedelic-related therapies are currently in development for TRD but have not yet been approved).

TRD is a disease with high unmet need and is associated with multiple serious public health implications.

The FDA and the EMA have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment).

A number of published sources estimate that at least 30% of persons with depression meet this definition.

There are many treatment paradigms that have been employed for the management of TRD.

In general, these treatment paradigms /therapies can be bucketed into categories of:

pharmacotherapies, somatic therapies and psychotherapeutic approaches.

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

• Pharmacotherapies :

antidepressants and antipsychotics indicated for use in major depressive disorder are frequently prescribed, combined or augmented with a second agent to treat TRD.

Additionally, mood stabilizers (e.g.

lithium) are utilized as treatments, alone or in combination for TRD.

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.

• Somatic Therapies :

multiple somatic therapies are used for the management of TRD such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS).

• Psychotherapeutic Approaches :

manual-based psychotherapies are not proven to be efficacious as a standalone intervention in TRD, but their efficacy in combination with antidepressants has been noted.

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 of products that may be similar to our product candidates or address similar markets.

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.

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.

Many of our competitors, including those mentioned below, 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.

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.

Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors.

These competitors also compete with Cyclerion in establishing clinical trial sites and participant registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

These competitors could also compete with us in establishing clinical trial sites and participant registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Competition can be viewed as through at least two lenses:

1) companies that are developing products with a different mechanism of action to address the same therapeutic need and 2) companies that are developing products that act through the same mechanism of action (i.e., sGC modulators).

Competition within target therapeutic areas .

We believe PTC Therapeutics, Travere Therapeutics, Dimerix Limited, Vertex Pharmaceuticals, Chinook Therapeutics, Boehringer Ingelheim, River 3 Renal Corp, Astellas, Pfizer, Eli Lilly, Novartis, AstraZeneca, Bayer and Merck are our most direct competitors with respect to praliciguat, and olinciguat.

Competition within the sGC mechanism .

There is one major competitor that is actively developing sGC modulators.

Bayer and Merck have an active collaboration on sGC stimulators, focused primarily on cardiovascular, pulmonary, and renal indications.

They have two approved sGC stimulators, ADEMPAS® (riociguat), indicated for pulmonary arterial hypertension (“PAH) and chronic thromboembolic pulmonary hypertension (“CTEPH”), which is a rare and potentially fatal form of elevated blood pressure in the lungs (known as pulmonary hypertension) and VERQUVO® (vericiguat) for heart failure with reduced ejection fraction (HFrEF).

We are not aware of any efforts to develop sGC modulators for treatment of CNS diseases.

Competition can also impact Tisento (in which we hold an equity interest), as well as companies which we have out-licensed or seek to out-license our product candidates.

To date, the product candidates we have sold to Tisento or out-licensed to Akebia are either in early stage clinical or pre-clinical stages or not yet received any approval allowing for the commercial sale of these product candidates.

Manufacturing

8 unchanged sentences

Employee Profile

During the year ended December 31, 2023, we initiated major reductions in our workforce in connection with the sale of the Transferred Assets to Tisento and change to the Company’s strategy.

As of December 31, 2023, we had one employee and several consultants.

We may in the future seek to expand our employee base and also outsource certain functions to other firms.

As of December 31, 2024, we had one employee and several consultants, including our Chief Financial Officer.

We may in the future seek to expand our employee base, hire additional consultants and also outsource certain functions to other firms.

Corporate Information

18 unchanged sentences

Risk Factors Summary

Risks Related to our Financial Position and Capital Needs

• We are a biopharmaceutical company with a limited operating history and no products approved for commercial sale.

5 unchanged sentences

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

• Our approach to the discovery and development of our product candidates may never lead to marketable products.

• 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.

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

• We may encounter substantial delays in our activities, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities in the development of our compounds.

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

• We may be unable to obtain regulatory approval for our product candidates and unable to generate product revenue.

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

• 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 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.

• We may not succeed in our pursuit of capital, capabilities, and transactions for the development and commercialization of our assets.

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

• The 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.

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

• We may enter into collaboration or license arrangements in the future that ultimately are not successful.

• We rely, and 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.

Risks Related to Reliance on Licensees, Tisento and Third Parties

• 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.

• 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 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.

If these third parties do not execute successfully, our business could be substantially harmed.

Risks Related to Intellectual Property

• 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.

5 unchanged sentences

• We may be subject to damages resulting from claims that we or our employees, consultants or advisors have wrongfully used or disclosed alleged trade secrets of their current or former employers.

Risks Related to the Future Commercialization of our Potential Future Product Candidates

• If the market opportunities for our product candidates are smaller than we estimate, our revenue and ability to achieve profitability may be harmed.

1 unchanged sentence

• 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 may harm our business.

• 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.

• We may need to expand our organization and we may experience difficulties in managing growth of our employee base.

• We will need to expand our organization and we may experience difficulties in managing growth of our employee base.

• We face potential product liability exposure, and, if claims are brought against us, we may incur substantial liability.

• 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;

limited to, regulatory investigations or actions;

fines and penalties;

6 unchanged sentences

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.

• 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.

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

• 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.

• The COVID-19 pandemic and future pandemics may disrupt our business, including our development activities.

Risks Related to Our Financial Position and Capital Needs

2 unchanged sentences

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.

We are developing a pipeline of sGC stimulators, but we have no products approved for commercial sale, and we have never generated revenue from product sales.

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.

9 unchanged sentences

Our net losses for the years ended December 31, 2024 and 2023 were $3.1 million and $5.3 million, respectively.

We expect to incur significant losses for at least 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, 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 European Medicines Agency (EMA), or other regulatory agencies, domestic or foreign, to perform clinical and other studies in addition to those that we currently anticipate.

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.

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.

There is substantial doubt about 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 product candidates.

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.

2 unchanged sentences

As of December 31, 2024, 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 for one year after the date the financial statements are issued, 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 beyond the second quarter, 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.

We intend to seek funds through collaborations, strategic alliances, or licensing arrangements with third parties.

Such agreements may adversely impact retained rights to our assets, technologies, future revenue streams and programs, especially those that receive regulatory approval.

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

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.

2 unchanged sentences

The sale of additional equity or convertible securities may 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.

We will need significant additional capital in the near term to continue our current plans.

No assurance can be given that we will be able to obtain such funds upon favorable terms and conditions, if at all.

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.

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.

Risks Related to our Business and Industry

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

We also intend to seek funds through collaborations, strategic alliances, or licensing arrangements with third parties.

Such agreements may adversely impact retained rights to our assets, technologies, future revenue streams and programs, especially those that receive regulatory approval.

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

Our approach to the discovery and development of product candidates for the treatment of serious diseases may never lead to marketable products.

5 unchanged sentences

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 and praliciguat (out-licensed to Akebia), our retained systemic sGC stimulators 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.

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.

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

1 unchanged sentence

Each product candidate must demonstrate an adequate benefit-risk profile for its intended use in its intended patient population.

In some instances, significant variability in safety or efficacy appear in different clinical studies of the same product candidate due to numerous factors,

including changes in study protocols, differences in the number and characteristics of the enrolled study participants, variations in the dosing regimen and other clinical study parameters or the dropout rate among study participants.

In some instances, significant variability in safety or efficacy appear in different clinical studies of the same product candidate due to numerous factors, including changes in study protocols, differences in the number and characteristics of the enrolled study participants, variations in the dosing regimen and other clinical study parameters or the dropout rate among study participants.

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

4 unchanged sentences

In the event of difficulties in enrolling participants in any clinical studies conducted on our product candidates, those clinical trials could be delayed or prevented from proceeding.

Identifying and qualifying participants to participate in any clinical studies of our product candidates would be critical to the success of those clinical trials as well as the product candidates we have out-licensed to Akebia and the Transferred Assets sold to Tisento.

Identifying and qualifying participants to participate in any clinical studies of our product candidates would be critical to the success of those clinical trials.

The timing of any clinical studies will depend in part on the speed at which participants can be recruited to participate in testing these product candidates.

5 unchanged sentences

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.

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.

19 unchanged sentences

• reports from nonclinical or clinical testing of other competing candidates that raise safety or efficacy concerns;

• cutbacks in funding for the FDA may result in delays in reviewing and approving applications;

• difficulties retaining participants who have enrolled in a clinical study but may be prone to withdraw due to rigors of the clinical studies, lack of efficacy, side effects, personal issues, or loss of interest.

9 unchanged sentences

Some may result in label restrictions.

Our current and any potential future product candidates, those licensed to Akebia and those sold to Tisento may cause serious side effects which could cause us, our licensees, Tisento, or regulatory authorities to interrupt, delay or halt clinical studies and could result in restrictive label language or delay or denial of regulatory approval.

Changes in regulatory requirements, FDA guidance or unanticipated events during nonclinical studies and clinical studies of our product candidates, those licensed to Akebia and those sold to Tisento may occur, which may result in changes to nonclinical or clinical study protocols or additional nonclinical or clinical study requirements, which could result in increased costs and could delay development timelines.

Our current and any potential future product candidates may cause serious side effects which could cause us, our licensees, Tisento, or regulatory authorities to interrupt, delay or halt clinical studies and could result in restrictive label language or delay or denial of regulatory approval.

Changes in regulatory requirements, FDA guidance or unanticipated events during nonclinical studies and clinical studies of our product candidates, which may result in changes to nonclinical or clinical study protocols or additional nonclinical or clinical study requirements, which could result in increased costs and could delay development timelines.

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.

5 unchanged sentences

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 countries.

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.

9 unchanged sentences

If we, our licensees or Tisento seek and are awarded orphan drug designation in the US and/or the EU based upon criteria in effect at the time, this designation may be rescinded if a similar drug or another therapy that confers a significant benefit over these product candidates is subsequently approved.

If these product

candidates were to fail to obtain orphan drug status, or lose such status after it is obtained, or the marketing exclusivity that such status provides, our business, prospects, financial condition and results of operations could be materially harmed.

If these product candidates were to fail to obtain orphan drug status, or lose such status after it is obtained, or the marketing exclusivity that such status provides, our business, prospects, financial condition and results of operations could be materially harmed.

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.

The COVID-19 pandemic and other future pandemics may disrupt our business, including our development activities.

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.

6 unchanged sentences

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 Our Reliance on Third Parties

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 intend in the future to seek 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.

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

will be successful.

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

2 unchanged sentences

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

Cyclerion is eligible to receive up to $12 million upon the initiation of a phase 2 clinical trial.

Cyclerion is eligible to receive up to $585 million in total potential future development, regulatory, and commercialization milestone payments.

Akebia will pay Cyclerion tiered royalty payments on net sales in certain major markets at percentages ranging from the mid-single digits to the high-teens, subject to certain reductions and offsets.

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.

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.

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

The agreement may be terminated by either party in the event of a material breach by the other party or by us in the event of certain patent disputes.

1 unchanged sentence

Akebia may at any time terminate the Akebia License Agreement upon 180 days written notice.

subject to Akebia’s obligation to grant Cyclerion a non-exclusive, royalty-free license, with the right

to grant multiple tiers of sublicenses, to certain licensed compounds or products as defined in the Akebia License Agreement as well as certain rights to regulatory submissions, product trademarks, contracts with third party suppliers and certain other rights.

subject to Akebia’s obligation to grant Cyclerion a non-exclusive, royalty-free license, with the right to grant multiple tiers of sublicenses, to certain licensed compounds or products as defined in the Akebia License Agreement as well as certain rights to regulatory submissions, product trademarks, contracts with third party suppliers and certain other rights.

Tisento may not be successful in developing any therapies and we may not realize any future value from the Tisento common stock we received under the Asset Purchase Agreement with Tisento.

35 unchanged sentences

These factors may materially impede the willingness or ability of third parties to complete quality nonclinical and clinical studies and may subject us to unexpected cost increases that are beyond our control.

Nevertheless, we may be responsible for ensuring that each of any future nonclinical and clinical studies is conducted in accordance with any applicable protocol, legal, regulatory and scientific requirements and standards, and our reliance on CROs and other third parties does not necessarily relieve us of our regulatory responsibilities.

Nevertheless, we may

be responsible for ensuring that each of any future nonclinical and clinical studies is conducted in accordance with any applicable protocol, legal, regulatory and scientific requirements and standards, and our reliance on CROs and other third parties does not necessarily relieve us of our regulatory responsibilities.

We, and any future CROs and other third parties are required to comply with regulations and guidelines, such as good laboratory practices (GLPs), good clinical practices (GCPs), and current Good Manufacturing Practices.

7 unchanged sentences

In addition, the CROs, or other third parties, may not perform all of their obligations under arrangements with us or our licensees or in compliance with regulatory requirements, but we may remain responsible and are subject to enforcement action that may include civil penalties and criminal prosecution for any violations of FDA laws and regulations during the conduct of clinical studies.

If the CROs, or our licensees, do not perform clinical studies in a satisfactory manner, breach their obligations to us or fail to comply with regulatory

requirements, the development and commercialization of our product candidates may be delayed, or our development program materially and irreversibly harmed.

If the CROs, or our licensees, do not perform clinical studies in a satisfactory manner, breach their obligations to us or fail to comply with regulatory requirements, the development and commercialization of our product candidates may be delayed, or our development program materially and irreversibly harmed.

We may not be able to control the amount and timing of resources these CROs or our licensees devote to our clinical products.

18 unchanged sentences

These agreements typically limit the rights of the third parties to use or disclose our confidential information, such as trade secrets and know-how.

Despite these contractual provisions, the need to share our confidential information with third parties increases the risk that confidential information such as trade secrets and know-how becomes known by our competitors, is inadvertently incorporated into the technology of others, or is

disclosed or used in violation of these agreements.

Given that our proprietary position is based, in part, on our confidential information including know-how and trade secrets, a competitor's discovery of our confidential information or other unauthorized use or disclosure could impair our competitive position and may have a material adverse effect on our business, prospects, financial condition and results of operations.

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 our 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.

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.

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 nineteen issued U.S.

patents, nine pending U.S.

We have 20 issued U.S.

patents, eleven pending U.S.

patents applications and numerous foreign patents and pending patent applications.

Patent families are filed either as utility US 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.

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.

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.

2 unchanged sentences

Moreover, patents, if issued, may be challenged, deemed unenforceable, invalidated or circumvented in the United States and abroad.

patents and patent applications may also be subject to interference, derivation, ex-parte reexamination, post-grant review, or inter-partes review proceedings, supplemental examination and challenges in district court.

Interference proceedings provoked by third parties or brought by us or our licensees may be necessary to determine the priority of inventions with respect to patents or patent applications.

20 unchanged sentences

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some confidential information could be compromised by disclosure during this type of litigation.

There could also be public announcements of the results of hearings, motions or other interim proceedings or developments.

There could also be public announcements of the results of hearings, motions or other interim

proceedings or developments.

If securities analysts or investors perceive these results to be negative, it would have a material adverse effect on the price of our common stock.

21 unchanged sentences

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.

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.

35 unchanged sentences

Moreover, the applicable time period or the scope of patent protection afforded could be less than we request.

If unable to obtain a patent term extension or the term of any such extension is less

than we request, the duration of patent protection obtained for our product candidates may not provide any meaningful commercial or competitive advantage, competitors may obtain approval of competing products earlier than they would otherwise be able to do so, and our ability to generate revenues could be harmed.

If unable to obtain a patent term extension or the term of any such extension is less than we request, the duration of patent protection obtained for our product candidates may not provide any meaningful commercial or competitive advantage, competitors may obtain approval of competing products earlier than they would otherwise be able to do so, and our ability to generate revenues could be harmed.

Changes in U.S.

14 unchanged sentences

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.

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.

7 unchanged sentences

The incidence and prevalence for all the conditions we aim to address with our current and any potential future programs vary considerably.

Projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates,

are based on beliefs and estimates.

Projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on beliefs and estimates.

These estimates have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect.

25 unchanged sentences

• the safety, efficacy, cost and other potential advantages of our approved product candidates compared to other available therapies;

• our ability to generate cost effectiveness data that supports a profitable price;

• our ability to obtain sufficient reimbursement and pricing by third-party payors and government authorities;

• the willingness of patients to pay out-of-pocket in the absence of sufficient payor coverage;

• the effectiveness of our sales and marketing strategies;

• our ability to generate cost effectiveness data that supports a profitable price;our ability to obtain sufficient reimbursement and pricing by third-party payors and government authorities;the willingness of patients to pay out-of-pocket in the absence of sufficient payor coverage;the effectiveness of our sales and marketing strategies;

• publicity concerning our product candidates or competing products and treatments.

4 unchanged sentences

Price controls may be imposed in certain markets, which may harm our future profitability.

Market acceptance and sales of any approved product candidates will depend significantly on the availability of adequate coverage and reimbursement from third-party payors and government authorities and may be affected by existing and future health care reform measures.

Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drugs they will pay for and establish reimbursement levels.

6 unchanged sentences

Obtaining coverage and reimbursement approval for a product from a government or other third-party payor is a time consuming and costly process that could require the provision of supporting scientific, clinical and cost-effectiveness data for the use of our product candidates to the payor.

We or our partners may not be able to provide data sufficient to gain acceptance with respect to coverage and reimbursement.

We or our partners may not be able to provide

data sufficient to gain acceptance with respect to coverage and reimbursement.

We cannot be sure that coverage or adequate reimbursement will be available for any of our product candidates.

8 unchanged sentences

Reference pricing used by various European Union member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce prices.

In some countries, we or our partners may be required to conduct a clinical trial or other

studies that compare the cost-effectiveness of our product candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval.

In some countries, we or our partners may be required to conduct a clinical trial or other studies that compare the cost-effectiveness of our product candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval.

Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries.

10 unchanged sentences

In May 2018, the General Data Protection Regulation, or the GDPR, took effect, increasing our obligations with respect to clinical studies conducted in the EEA and increasing the scrutiny applied by clinical study sites located in the EEA to transfers of personal data from such sites to countries that are considered by the European Commission to lack an adequate level of data protection, such as the United States.

The compliance obligations imposed by the GDPR may increase our cost of doing business.

The compliance obligations

imposed by the GDPR may increase our cost of doing business.

In addition, the GDPR imposes substantial fines for breaches of data protection requirements, and it confers a private right of action on data subjects for breaches of data protection requirements.

4 unchanged sentences

Moreover, achieving and sustaining compliance with applicable federal and state privacy, security, fraud and reporting laws may prove costly.

more effective than ours, which may harm our ability, or a licensee's ability, to successfully market or commercialize any product candidates we may develop and ultimately harm our financial condition.

We face significant competition in an environment of rapid technological and scientific change, and our competitors may achieve regulatory approval before us or develop therapies that are safer, more advanced or more effective than ours, which may harm our ability, or a licensee's ability, to successfully market or commercialize any product candidates we may develop and ultimately harm our financial condition.

Our future success depends on our ability, or a licensee's ability, to demonstrate and maintain a competitive advantage with respect to the design, development and commercialization of our product candidates.

3 unchanged sentences

Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing, and commercialization.

Bayer AG and Merck & Co., Inc.

(“Bayer/Merck”), have an active collaboration on sGC stimulators including ADEMPAS® (riociguat), which has been approved for the treatment of Pulmonary Arterial Hypertension, (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Verquvo® (vericiguat), which is approved for the treatment of heart failure with reduced ejection fraction.

Such sGC products may compete directly with our own product candidates in our non-CNS target indications.

Because Bayer/Merck already have experience conducting successful clinical trials and obtaining regulatory approvals for an sGC product, they may be able to conduct clinical trials and obtain regulatory approvals for additional product candidates and target indications more quickly or efficiently than we or our licensees can.

If our product candidates do not obtain regulatory approvals in target indications prior to these or any other competing product candidates, or if our product candidates do not demonstrate superior efficacy, safety or tolerability compared to these and any other approved therapeutics for our target indications, then those product candidates may not be able to compete effectively.

8 unchanged sentences

Our revenue prospects could be affected by changes in healthcare spending and policy in the United States and abroad.

payment for health care products and services could harm our business, operations and financial condition.

We operate in a highly regulated industry and new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or decisions, related to health care availability, the method of delivery or payment for health care products and services could harm our business, operations and financial condition.

There is significant interest in promoting health care reform, as evidenced by the enactment in the United States of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act in 2010 and in reducing the costs of certain prescription drugs as evidenced by the Inflation Reduction Act of 2022.

41 unchanged sentences

Risks Related to Our Business Operations

Our prospects for success depend on our ability to retain Regina Graul, our President and in the future to attract, retain and motivate qualified personnel.

Our prospects for success depend on our ability to retain Regina Graul, our President and Chief Executive Officer and in the future to attract, retain and motivate qualified personnel.

We are highly dependent on Regina Graul, Ph.D.

1 unchanged sentence

Despite our efforts to retain valuable employees, members of our management, scientific and development teams may terminate their employment with us on short notice.

Our success also depends on our ability to in the future attract, retain and motivate highly skilled junior, mid-level and senior managers as well as junior, mid-level and senior scientific and medical personnel.

Our success also depends on our ability in the future to attract, retain and motivate highly skilled junior, mid-level and senior managers as well as junior, mid-level and senior scientific and medical personnel.

We may not be able to attract or retain qualified management and scientific personnel in the future due to the competition for a limited number of qualified personnel among biopharmaceutical, biotechnology, pharmaceutical and other businesses.

2 unchanged sentences

Some of these characteristics may be more appealing to high quality candidates than what we may be able to offer.

The failure to succeed in nonclinical or clinical studies may make it more challenging to recruit and retain qualified personnel.

The failure to succeed in nonclinical

or clinical studies may make it more challenging to recruit and retain qualified personnel.

In addition, in order to induce employees to continue their employment with us, we have provided equity awards that vest over time and the value to our employees of such equity awards may be significantly affected by movements in our stock price that are beyond our control and may be at any time insufficient to counteract more lucrative offers from other companies.

31 unchanged sentences

If we fail to maintain proper and effective internal controls, our ability to produce accurate and timely financial statements could be impaired, which could result in sanctions or other penalties that would harm our business.

We are subject to the reporting requirements of the Securities Exchange Act of 1934, or The Exchange Act, the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, and the rules and regulations of the Nasdaq Capital Market.

We are an “emerging growth company” and a “smaller reporting company.” For so long as we remain either an emerging growth company or a smaller reporting company, we will be exempt from Section 404(b) of the Sarbanes-Oxley Act, which requires auditor attestation to the effectiveness of internal control over financial reporting.

We will cease to be an emerging growth company on the date that is the earliest of (i) the last day of the fiscal year in which we have total gross annual revenues of $1.07 billion or more;

(ii) December 31, 2024, the last day of our fiscal year following the fifth anniversary of the date of the Separation;

(iii) the date on which we have

issued more than $1 billion in nonconvertible debt during the previous three years;

or (iv) the date on which we are deemed to be a large accelerated filer under the rules of the SEC.

Even after we no longer qualify as an emerging growth company, we may still qualify as a smaller reporting company, which would allow us to take advantage of many of the same exemptions from disclosure requirements, including exemption from compliance with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.

We cannot predict if investors will find our common stock less attractive because we may rely on the exemptions available to us as an emerging growth company and/or smaller reporting company.

We are a “smaller reporting company.” For so long as we remain a smaller reporting company, we will be exempt from Section 404(b) of the Sarbanes-Oxley Act, which requires auditor attestation to the effectiveness of internal control over financial reporting.

As a smaller reporting company, we are exempt from compliance with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.

We cannot predict if investors will find our common stock less attractive because we may rely on the exemptions available to us as a smaller reporting company.

If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.

1 unchanged sentence

Beginning with our annual report on Form 10-K for the fiscal year ended December 31, 2024, we must include a management assessment of the effectiveness of our internal control over financial reporting.

As of the expiration of our emerging growth company status, which status will end on December 31, 2024 and smaller reporting company status, we will be broadly subject to enhanced reporting and other requirements under the Exchange Act and Sarbanes-Oxley Act.

As of the expiration of our smaller reporting company status, we will be broadly subject to enhanced reporting and other requirements under the Exchange Act and Sarbanes-Oxley Act.

We have engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging.

7 unchanged sentences

If that were to happen, our business, prospects, financial condition and results of operations could be harmed, our investors could lose confidence in our reported financial information, the market price of our stock could decline, and we could be subject to sanctions or investigations by the SEC or other regulatory authorities.

Unfavorable global economic 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.

A severe or prolonged economic downturn 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.

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.

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.

A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption.

30 unchanged sentences

A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to provide our products.

We may expend significant resources or modify our

business activities (including our clinical trial activities) to try to protect against security incidents.

Certain data privacy and security obligations require us to implement and maintain specific security measures, industry-standard or reasonable security measures to protect our information technology systems and sensitive information.

We may expend significant resources or modify our business activities (including our clinical trial activities) to try to protect against security incidents.

Certain data privacy and security

obligations require us to implement and maintain specific security measures, industry-standard or reasonable security measures to protect our information technology systems and sensitive information.

Applicable data security and public company disclosure obligations may require us to notify relevant stakeholders of certain security incidents, including affected individuals, customers, regulators and investors.

28 unchanged sentences

Additionally, we are subject to the risk that a person could allege such fraud or other misconduct, even if none occurred.

If any such actions are

instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions, possible exclusions from participation in Medicare, Medicaid and other U.S.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have

a significant impact on our business, including the imposition of significant fines or other sanctions, possible exclusions from participation in Medicare, Medicaid and other U.S.

federal healthcare programs, contractual damages and reputational harm.

27 unchanged sentences

If the Company does not regain compliance with the Bid Price Requirement in the future, the Company's stock will again be subject to delisting.

As a result of amendments in October 2024 to the NASDAQ

delisting procedures, NASDAQ now may automatically delist companies which conduct multiple reverse stock splits in any 12-month period.

The Company intends to monitor the closing bid price of its common stock and may, if appropriate, consider available options to regain compliance with the Bid Price Requirement, including initiating a reverse stock split.

1 unchanged sentence

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.

Our common stock has a limited trading history and the market price has fluctuated widely, and may in the future fluctuate widely, depending upon many factors, some of which are beyond our control, including the following:

• a relatively low-volume trading market for our shares of common stock may result, which could cause trades of small blocks of shares to have a significant impact on the price of our shares of common stock;

The market price for our common stock has fluctuated widely, and may in the future fluctuate widely, depending upon many factors, some of which are beyond our control, including the following:

• failure to raise additional capital on a timely basis and the terms on which we raise any capital;

• a relatively low public float for our shares of common stock, which could cause trades of small blocks of shares to have a significant impact on the price of our shares of common stock;

• results and timing of nonclinical studies and clinical studies of our product candidates;

2 unchanged sentences

• failure to adequately protect our trade secrets;

• our inability to raise additional capital and the terms on which we raise it;

• commencement or termination of any strategic partnership or licensing arrangement;

9 unchanged sentences

• 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;

42 unchanged sentences

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

We are in the process of updating our analysis of owner shifts to determine whether an ownership change occurred since March 30, 2019.

It is possible that we have experienced an ownership change in the past.

In addition, we may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control.

In addition, we may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control, as well as the issuance of additional securities if we are successful in raising equity capital.

As a result, our federal NOL carryforwards may be subject to a percentage limitation if used to offset income in tax years following an ownership change.

In addition, it is possible that we have in the past undergone, and in the future may undergo, additional ownership changes that could limit our ability to use all of our pre-change NOL carryforwards and other pre-change tax attributes (such as research tax credits) to offset our post-change

income or taxes.

Similar provisions of state tax law may also apply to limit our use of accumulated state tax attributes.

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.

6 unchanged sentences

The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us, our business, our market or our competitors.

Currently, no industry analysts cover our stock.

If securities or industry analysts fail to initiate coverage of our stock, the lack of exposure to the market could cause our stock price or trading volume to decline.

13 unchanged sentences

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

provisions, alone or together, could delay hostile takeovers and changes in control of our company or changes in our management.

These provisions, alone or together, could delay hostile takeovers and changes in control of our company or changes in our management.

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.

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.

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.

35 unchanged sentences

Our board of directors addresses our cybersecurity risk management as part of its general oversight function.

Commencing in 2024, our Audit Committee, on behalf of the board of directors, provides oversight of our cybersecurity risk management program .

Our cybersecurity risk assessment and management processes are implemented and maintained by various members of our management team and IT consultants, which includes individuals who have a diverse combination of relevant expertise, experience, education and training.

7 unchanged sentences

The board also receives various summaries and/or presentations related to cybersecurity threats, risks and mitigation.

Commencing in 2024, our Audit Committee is taking the lead on behalf of the board of directors on oversight of our cybersecurity risk management program.

In April 2021 we completed our exit from our prior laboratory and office facilities in Cambridge Massachusetts and moved to an operating model under which we outsource our research and development laboratory work, and we are currently leasing office space on an “as-needed” basis.

5 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