Cyclerion Therapeutics Reports Second Quarter 2021 Financial Results and Corporate Update Continuing to progress clinical development of CY6463, a first-in-class, CNS-penetrant soluble guanylate cyclase (sGC) stimulator

Cyclerion Therapeutics Reports Second Quarter 2021 Financial Results and Corporate Update

Continuing to progress clinical development of CY6463, a first-in-class, CNS-penetrant soluble guanylate cyclase (sGC) stimulator for the treatment of neurological diseases associated with cognitive impairment

Advancing CY3018, a differentiated, next-generation, CNS-penetrant sGC stimulator, in IND-enabling studies

CAMBRIDGE, Mass., July 29, 2021 - Cyclerion Therapeutics, Inc. (Nasdaq: CYCN), a clinical-stage biopharmaceutical company on a mission to develop treatments that restore cognitive function, today reported financial results for the second quarter 2021 and provided general corporate and pipeline updates.

"During the first half of the year we have made significant progress advancing our lead program CY6463 into clinical development for multiple neurological indications where we believe we could have a meaningful therapeutic impact. This positive momentum in the clinic includes the advancement of the clinical studies in participants with Alzheimer's disease with vascular pathology (ADv) and Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) and the initiation of start-up activities for a clinical study in participants with Cognitive Impairment Associated with Schizophrenia (CIAS)," said Peter Hecht, Ph.D., Chief Executive Officer of Cyclerion. "We have also conducted additional preclinical work to support the advancement of CY3018, a differentiated, next-generation, CNS-penetrant sGC stimulator, into clinical development for specific serious neurological conditions."

Recent Program and Business Updates

Second Quarter 2021 Financial Results

CY6463 is the first CNS-penetrant sGC stimulator to be developed as a symptomatic and potentially disease-modifying therapy for serious CNS diseases. Nitric oxide (NO) is one of several fundamental neurotransmitters, but it has yet to be leveraged for its full CNS therapeutic potential. CY6463 stimulates sGC, a signaling enzyme that responds to the presence of NO, to enhance the body's natural ability to produce cyclic guanosine monophosphate (cGMP), an important signaling molecule that regulates diverse and critical biological functions in the CNS including neuronal function, neuroinflammation, cellular bioenergetics, and vascular dynamics. Impaired NO-sGC-cGMP signaling is believed to play an important role in the pathogenesis of many neurodegenerative and neuropsychiatric diseases. Agents that stimulate sGC to produce cGMP may compensate for deficient NO signaling.

About Cyclerion Therapeutics

Cyclerion Therapeutics is a clinical-stage biopharmaceutical company on a mission to develop treatments that restore cognitive function. Cyclerion is advancing novel, first-in-class, CNS-penetrant, sGC stimulators that modulate a key node in a fundamental CNS signaling pathway. The multidimensional pharmacology elicited by the stimulation of sGC has the potential to impact a broad

range of CNS diseases. The most advanced compound, CY6463, has shown rapid improvement in biomarkers associated with cognitive function and is currently in clinical development for Alzheimer's Disease with Vascular pathology (ADv), Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS), and Cognitive Impairment Associated with Schizophrenia (CIAS). Cyclerion is also advancing CY3018, a next-generation sGC stimulator.

Forward Looking Statement

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties and include, among other things, whether the praliciguat out-license will result in the creation of any therapies for the treatment of patients with kidney disease; the uncertain utility, development, promise, and commercialization of praliciguat; and whether any development, regulatory and commercialization milestones or royalty payments provided for in the agreement with Akebia will be achieved. We may, in some cases use terms such as "predicts," "believes," "potential," "continue," "anticipates," "estimates," "expects," "plans," "intends," "may," "could," "might," "likely," "will," "should" or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks listed under the heading "Risk Factors" and elsewhere in our 2020 Form 10-K filed on February 25, 2021, and our subsequent SEC filings including the Form 10-Qs filed on April 30, 2021 and July 29, 2021. Investors are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and Cyclerion undertakes no obligation to update these forward-looking statements, except as required by law.

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