UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38787 CYCLERION THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Massachusetts (State or other jurisdiction of incorpor ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other juri ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdict ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdic ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of registrant as specified in its charter) Massachusetts (State or other jurisdiction of incorpor ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, no par value CYCN The Nasdaq Stock Market LLC (Nasdaq Global Select Market) FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transit ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdict ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-38787 CYCLERION THERAPEUTICS, INC. (Exact Name of Registrant as Specified in its Charter) Massachusetts (State or other jurisdic ...

[Business Overview](index=5&type=section&id=Item%201.%20Business) Cyclerion Therapeutics, a clinical-stage biopharmaceutical company, focuses on developing CNS treatments, with lead asset CY6463 for MELAS and ADv, and outsources all manufacturing [Research and Development Programs](index=6&type=section&id=Research%20and%20Development%20programs) The company's R&D focuses on CNS programs, led by CY6463 in Phase 2a for MELAS and planned for ADv, while non-CNS assets are available for out-licensing - The lead asset, **CY6463**, a CNS-penetrant sGC stimulator, is in development for serious CNS diseases, with positive Phase 1 results announced in October 2020[24](index=24&type=chunk)[26](index=26&type=chunk) - A **Phase 2a clinical trial in MELAS** has been initiated, and a **Phase 2a trial in ADv** is planned for mid-2021, supported by a **$2 million grant** from the Alzheimer's Association[27](index=27&type=chunk) - Non-CNS assets, **praliciguat and olinciguat**, have completed Phase 2 studies and are available for out-licensing, being outside the company's strategic focus[29](index=29&type=chunk) [Intellectual Property](index=7&type=section&id=Intellectual%20Property) The company protects its technology through owned patents and trade secrets, with CY6463 patents expiring in 2037 and other assets extending into the 2030s - The company owns its intellectual property, comprising **17 issued U.S. patents** and numerous pending applications domestically and abroad[34](index=34&type=chunk)[35](index=35&type=chunk) - The **CY6463 patent portfolio** includes two issued U.S. patents covering the compound and compositions, expiring in **2037**[37](index=37&type=chunk)[38](index=38&type=chunk) - The **praliciguat and olinciguat patent portfolios** include multiple U.S. patents expiring between **2031 and 2037**[40](index=40&type=chunk)[41](index=41&type=chunk)[44](index=44&type=chunk) [Government Regulation](index=10&type=section&id=Government%20Regulation) The company's drug development is subject to extensive FDA regulation, involving nonclinical studies, INDs, multi-phase clinical trials, NDA submission, and post-approval compliance, with potential for expedited review designations - The drug approval process requires extensive nonclinical studies, an IND submission, and multi-phase clinical trials to establish safety and efficacy before NDA submission to the FDA[54](index=54&type=chunk)[59](index=59&type=chunk) - The FDA offers programs like **Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review** to expedite development and review for serious conditions[69](index=69&type=chunk)[71](index=71&type=chunk)[72](index=72&type=chunk) - **Orphan Drug Designation** provides **seven years of market exclusivity** for drugs treating rare diseases affecting fewer than **200,000 people** in the U.S[67](index=67&type=chunk)[68](index=68&type=chunk) - Post-approval, the company is subject to ongoing FDA regulation, including recordkeeping, adverse event reporting, and **cGMP compliance**[79](index=79&type=chunk)[80](index=80&type=chunk) [Competition](index=15&type=section&id=Competition) The company faces significant competition, primarily from Bayer/Merck in sGC modulators, and from companies developing treatments for MELAS and Alzheimer's Disease, where no specific ADv treatments are approved - The primary competitor in the sGC modulator space is the **Bayer/Merck collaboration**, with two approved non-CNS products, **ADEMPAS® and VERQUVO®**[96](index=96&type=chunk) - For MELAS, there are no approved treatments, but competitors in clinical development include **PTC Therapeutics, Khondrion B.V, and Abliva AB**[92](index=92&type=chunk) - For ADv, there are no approved treatments, but competition includes approved AD symptom treatments and late-stage AD candidates from companies like **Biogen, Eli Lilly, and Roche**[93](index=93&type=chunk)[95](index=95&type=chunk) [Manufacturing and Human Capital](index=17&type=section&id=Manufacturing) The company outsources all manufacturing to third-party CMOs and, as of December 31, 2020, had approximately 34 employees after a workforce reduction - The company relies entirely on **third-party contract manufacturing organizations (CMOs)** for all clinical and nonclinical supply needs, owning no manufacturing facilities[98](index=98&type=chunk) - As of **December 31, 2020**, the company had approximately **34 employees**, with an additional **17 employees transitioning out** in Q1 2021 due to a 2020 workforce reduction[102](index=102&type=chunk) [Risk Factors](index=18&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including financial losses, high CNS drug development failure rates, clinical trial delays, regulatory uncertainties, heavy reliance on third parties, and post-separation tax and strategic restrictions [Financial Position and Capital Needs](index=20&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Capital%20Needs) As a clinical-stage company with no product revenue, Cyclerion has incurred significant net losses and will require substantial additional funding to advance its pipeline - The company is a clinical-stage biopharmaceutical company with no approved products and has never generated revenue from product sales[120](index=120&type=chunk) Net Loss | Fiscal Year | Net Loss (in millions USD) | | :--- | :--- | | 2020 | $77.8 | | 2019 | $123.0 | - As of **December 31, 2020**, the company had approximately **$54.4 million in cash and cash equivalents** and will require significant additional funding[128](index=128&type=chunk) [Business and Industry Risks](index=21&type=section&id=Risks%20Related%20to%20our%20Business%20and%20Industry) The company faces inherent risks in CNS drug development due to biological complexities, high clinical trial failure rates, potential COVID-19 disruptions, and the lengthy, unpredictable regulatory approval process - CNS therapy development is challenging due to the **blood-brain barrier** and often poor translatability from nonclinical to clinical results[132](index=132&type=chunk) - The **COVID-19 pandemic** continues to risk disrupting clinical development, potentially delaying patient enrollment and trial execution[137](index=137&type=chunk)[138](index=138&type=chunk) - The regulatory approval process is lengthy and unpredictable, with no guarantee of product candidate approval[143](index=143&type=chunk)[144](index=144&type=chunk) [Reliance on Third Parties](index=26&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The company's business model heavily relies on third parties for out-licensing, clinical trials (CROs), and manufacturing (CMOs), posing risks to performance, quality, and regulatory compliance due to less direct control - Failure to find a partner for out-licensing **praliciguat** would adversely affect the prospect of realizing financial benefit from the asset[160](index=160&type=chunk) - The company relies on **third-party CROs** for clinical studies and **CMOs** for drug manufacturing, depending on their performance and compliance with regulations like GCP and cGMP[164](index=164&type=chunk)[170](index=170&type=chunk)[171](index=171&type=chunk) - Reliance on third parties necessitates sharing confidential information and trade secrets, increasing the risk of misappropriation or unauthorized disclosure[174](index=174&type=chunk)[175](index=175&type=chunk) [Risks Related to the Separation from Ironwood](index=43&type=section&id=Risks%20Related%20to%20the%20Separation) The 2019 separation from Ironwood poses risks including unrepresentative historical financials, potential IRS challenge to tax-free status leading to significant indemnification liabilities, and restrictions on strategic transactions - Historical financial information may not be representative of future results due to expense allocations from Ironwood prior to the separation[286](index=286&type=chunk)[287](index=287&type=chunk) - If the separation from Ironwood is deemed taxable, Cyclerion could be required to indemnify Ironwood for significant, uncapped tax liabilities[288](index=288&type=chunk)[294](index=294&type=chunk) - To preserve tax-free status, the tax matters agreement prohibits Cyclerion from certain transactions, like a **3% or more change of ownership**, for two years post-distribution[295](index=295&type=chunk) [Management's Discussion and Analysis (MD&A)](index=51&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations.) This section provides management's analysis of the company's financial condition and results for 2020 versus 2019, highlighting decreased operating expenses, sufficient cash for 12 months, and details on R&D and liquidity sources [Results of Operations (2020 vs. 2019)](index=55&type=section&id=Results%20of%20Operations) In fiscal year 2020, the company reported a net loss of $77.8 million, a 37% improvement from 2019, driven by significant reductions in R&D and G&A expenses, and gains from lease modifications Key Financial Metrics | Financial Metric | 2020 (in thousands USD) | 2019 (in thousands USD) | Change ($ in thousands USD) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Revenue from related party | $2,296 | $4,507 | $(2,211) | (49)% | | Research and development | $56,414 | $95,140 | $(38,726) | (41)% | | General and administrative | $28,816 | $34,404 | $(5,588) | (16)% | | **Net loss** | **$(77,802)** | **$(123,008)** | **$45,206** | **(37)%** | R&D External Costs by Program | R&D External Costs by Program | 2020 (in thousands USD) | 2019 (in thousands USD) | | :--- | :--- | :--- | | CY6463 | $5,561 | $4,278 | | Praliciguat | $311 | $13,344 | | Olinciguat | $6,868 | $13,064 | | Discovery research | $1,218 | $1,293 | - The decrease in R&D expenses was primarily due to reduced spending on **praliciguat studies (down $13.0 million)** and **olinciguat studies (down $6.2 million)**, alongside lower personnel and facility costs[363](index=363&type=chunk) - The company recorded a **net gain on lease modification of $1.7 million** and **sublease termination income of $2.9 million** in 2020[365](index=365&type=chunk)[367](index=367&type=chunk) [Liquidity and Capital Resources](index=56&type=section&id=Liquidity%20and%20Capital%20Resources) As of December 31, 2020, the company held $54.4 million in cash, which management deems sufficient for the next 12 months, following 2020 financing activities including a private placement and a PPP loan - The company had **$54.4 million in unrestricted cash and cash equivalents** as of **December 31, 2020**[373](index=373&type=chunk) - Management concluded that existing cash and cash equivalents are sufficient to fund planned operations for at least the **next 12 months** from the report filing date[374](index=374&type=chunk)[387](index=387&type=chunk) - In 2020, the company raised approximately **$24.3 million** via a private placement, received a **$3.5 million PPP loan**, and established a **$50.0 million ATM offering**[370](index=370&type=chunk)[371](index=371&type=chunk)[382](index=382&type=chunk) Cash Flow Summary | Cash Flow Summary | 2020 (in thousands USD) | 2019 (in thousands USD) | | :--- | :--- | :--- | | Net cash used in operating activities | $(72,490) | $(102,215) | | Net cash provided by (used in) investing activities | $18 | $(6,715) | | Net cash provided by financing activities | $28,090 | $211,571 | [Controls and Procedures](index=60&type=section&id=Item%209A.%20Controls%20and%20Procedures.) Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2020, with no auditor attestation required for an emerging growth company - Management concluded that the company's **disclosure controls and procedures were effective** as of **December 31, 2020**[408](index=408&type=chunk) - Based on its assessment, management concluded that the company's **internal control over financial reporting was effective** as of **December 31, 2020**[413](index=413&type=chunk) - This annual report does not include an auditor's attestation report on internal control over financial reporting, as permitted for **"emerging growth companies"**[415](index=415&type=chunk) [Financial Statements and Notes](index=66&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data.) This section presents the company's audited consolidated financial statements for 2020 and 2019, along with detailed notes on accounting policies, the Ironwood separation impact, lease modifications, share-based compensation, income taxes, and workforce reductions [Consolidated Financial Statements](index=68&type=section&id=Consolidated%20Financial%20Statements) As of December 31, 2020, the company reported total assets of $115.4 million, total liabilities of $55.9 million, a net loss of $77.8 million, and $72.5 million in net cash used in operating activities Balance Sheet Highlights (Dec 31, 2020) | Balance Sheet Highlights (Dec 31, 2020) | Amount (in thousands USD) | | :--- | :--- | | Cash and cash equivalents | $54,395 | | Total assets | $115,378 | | Total liabilities | $55,885 | | Total stockholders' equity | $59,493 | Statement of Operations Highlights (FY 2020) | Statement of Operations Highlights (FY 2020) | Amount (in thousands USD) | | :--- | :--- | | Total cost and expenses | $83,561 | | Loss from operations | $(81,265) | | Net loss | $(77,802) | | Net loss per share | $(2.56) | [Selected Notes to Financial Statements](index=72&type=section&id=Selected%20Notes%20to%20Financial%20Statements) Key financial notes confirm no substantial doubt about going concern, detail 2020 lease amendments yielding $1.7 million gain and $2.9 million income, describe a $5.0 million workforce reduction, and disclose fully offset NOL carryforwards - Management concluded no substantial doubt exists regarding the company's ability to continue as a **going concern** for at least one year from the financial statements' issuance[486](index=486&type=chunk)[488](index=488&type=chunk) - In 2020, two lease amendments resulted in a **net gain on modification of $1.7 million**, and a sublease termination generated **$2.9 million in net income**[518](index=518&type=chunk)[519](index=519&type=chunk)[520](index=520&type=chunk) - A **workforce reduction** in November 2020 impacted approximately **48 employees** with an estimated cost of **$5.0 million**[629](index=629&type=chunk)[630](index=630&type=chunk) - As of **December 31, 2020**, the company had federal and state **NOL carryforwards** of approximately **$98.8 million and $98.9 million**, respectively, fully offset by a valuation allowance[618](index=618&type=chunk)[620](index=620&type=chunk)

Research and Development Expenses - The company reported research and development expenses of $13.703 million for the three months ended September 30, 2020, compared to $22.295 million for the same period in 2019, representing a decrease of approximately 38.8%[152] - For the nine months ended September 30, 2020, total research and development expenses were $44.322 million, down from $74.458 million in 2019, indicating a reduction of about 40.5%[152] - The external costs related to the IW-6463 product pipeline were $1.502 million for the three months ended September 30, 2020, compared to $1.559 million in 2019, showing a slight decrease of 3.6%[152] - Olinciguat, another product candidate, incurred external costs of $2.012 million for the three months ended September 30, 2020, down from $2.891 million in 2019, reflecting a decrease of approximately 30.3%[152] - Praliciguat's external costs were $53,000 for the three months ended September 30, 2020, significantly lower than $2.575 million in the same period of 2019, indicating a decrease of about 98%[152] - The company reported total product pipeline external costs of $4.108 million for the three months ended September 30, 2020, compared to $7.389 million in 2019, a decrease of approximately 44.5%[152] - Personnel and related internal costs allocated to research and development were $6.214 million for the three months ended September 30, 2020, down from $9.517 million in 2019, a reduction of about 34.5%[152] - Facilities and other costs related to research and development were $3.381 million for the three months ended September 30, 2020, compared to $5.389 million in 2019, representing a decrease of approximately 37.2%[152] - Research and development expenses decreased by approximately $8.6 million (39%) for the three months ended September 30, 2020, and by approximately $30.1 million (40%) for the nine months ended September 30, 2020, primarily due to lower average headcount and reduced external research costs[167][168] Clinical Trials and Product Development - The company plans to begin enrolling participants in the Phase 2 clinical trial for MELAS and aims to initiate a Phase 2 trial for Alzheimer's disease with vascular pathology in H1 2021[147] - As of September 30, 2020, the company had ongoing studies in various clinical trial stages, with significant spending on clinical research organizations[202] Financial Performance - Net loss for the three months ended September 30, 2020 was $18.8 million, a decrease of $8.5 million (31%) compared to the same period in 2019, and for the nine months ended September 30, 2020, the net loss was $58.6 million, a decrease of $38.4 million (40%) compared to the prior year[166] - Cash provided by financing activities for the nine months ended September 30, 2020 was $27.9 million, a significant decrease of $183.5 million (87%) compared to $211.4 million in the same period in 2019[186] - Net cash used in operating activities was $58.4 million for the nine months ended September 30, 2020, a decrease of $21.6 million (27%) compared to the same period in 2019[186] Cash and Funding - As of September 30, 2020, the company had approximately $66.8 million of unrestricted cash and cash equivalents, which are expected to fund operations into the fourth quarter of 2021[183][184] - The company raised approximately $24.3 million in a private placement of common stock on July 29, 2020, with no material fees or commissions related to the transaction[180] - The company anticipates principal uses of cash in the future will be to fund operations, working capital needs, capital expenditures, and other general corporate purposes[182] - The company received approximately $3.5 million in loan proceeds under the Paycheck Protection Program with a stated interest rate of 1.0% per annum[190] - The loan's principal and accrued interest are forgivable if proceeds are used for eligible purposes and payroll levels are maintained over a 24-week period[191] - As of September 30, 2020, the company expects existing cash and cash equivalents to fund planned operating expenses at least into Q4 2021[193] - Future funding requirements may fluctuate significantly based on the scope and costs of research and development activities[194] - The company may need to finance cash needs through public or private equity offerings, debt financings, or collaborations[198] General and Administrative Expenses - General and administrative expenses increased by approximately $0.9 million (13%) for the three months ended September 30, 2020, but decreased by approximately $5.5 million (20%) for the nine months ended September 30, 2020, mainly due to non-recurring costs associated with the Separation recorded in the prior period[170][171] Operational Changes - The company incurred additional ongoing operating expenses to operate as an independent publicly traded company following the Separation[203] - The Ironwood Transition Services Agreement, which provided corporate functions, was completed and terminated as of March 31, 2020[206] Risk and Compliance - The company emphasizes that securing regulatory approvals for new drugs is a lengthy and costly process, and any delays could materially affect product development efforts[152] - The company does not have off-balance sheet arrangements that expose it to financing, liquidity, market, or credit risk[208] - The company is classified as a smaller reporting company and is not required to provide certain market risk disclosures[210]