SEC Filing | Cyclerion Therapeutics, Inc.

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): July 9, 2020

CYCLERION THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Massachusetts	001-38787	83-1895370
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification Number)

301 Binney Street

Cambridge, Massachusetts 02142

(Address of principal executive offices, including Zip Code)

Registrant’s telephone number, including area code: (857) 327-8778)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

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)

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company x

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

Item 2.02

Results of Operations and Financial Condition.

As described in Item 7.01 below, on July 9, 2020, Cyclerion Therapeutics, Inc. (the “Company”) released a corporate slide presentation. The presentation included preliminary information that, as of June 30, 2020, the Company’s unaudited cash, cash equivalents and restricted cash balance was approximately $61 million and that the Company anticipates that this amount will be sufficient to fund planned operating expenses and capital expenditure requirements into the second half of 2021.

The foregoing information constitutes unaudited and preliminary estimates that (i) represent the most current information available to management as of the date of the presentation, (ii) are subject to completion of financial closing and procedures that could result in significant changes to the estimated amounts, and (iii) do not present all information necessary for an understanding of the Company’s financial condition as of, and its results of operations for the quarter ended June 30, 2020. Accordingly, undue reliance should not be placed on such estimates.

The information set forth in this Item 2.02 is being furnished pursuant to Item 2.02 of Form 8-K and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and it shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or under the Exchange Act, whether made before or after the date hereof, except as expressly provided by specific reference in such a filing.

Item 7.01

Regulation FD Disclosure.

On July 9, 2020, the Company released a corporate slide presentation that included the following updates:

Central Nervous System: IW-6463

Dosing has been completed in the ongoing IW-6463 translational pharmacology clinical study. Topline study data are expected in late summer 2020.

The Company anticipates initiating two parallel exploratory Phase 2 studies of IW-6463 to evaluate safety and a variety of efficacy measures, including engagement of CNS biomarkers using novel trial designs in Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS) and Alzheimer's disease with vascular features (ADv). These studies are designed to de-risk and direct future development in CNS diseases.

Sickle cell disease: olinciguat

The seventy subjects enrolled in the olinciguat Phase 2 STRONG SCD study in patients with sickle cell disease have completed their dosing period.

Topline study results are expected in late Q3 2020.

Praliciguat out-licensing

The Company remains in ongoing discussions to out-license global rights to praliciguat, its oral once-daily systemic sGC stimulator.

In those discussions, the Company has expanded beyond cardiometabolic disorders to additional indications in which sGC stimulators have shown efficacy.

Cyclerion can offer no assurances on the prospects or timing of any partnership or licensing transactions generally, or specifically on praliciguat.

A copy of the corporate slide presentation is attached hereto as Exhibit 99.1 and is incorporated by reference into this Current Report on Form 8-K. The presentation is also posted to the Company’s website, www.cyclerion.com. The Company plans to use its website to disseminate future updates to the presentation and may not necessarily file or furnish a Form 8-K alerting investors if the presentation is updated.

In addition, the Company hosted a webcast investor event on July 9, 2020 from 8:15 a.m. to 9:30 a.m. Eastern Time focused on IW-6463, the Company’s investigational, orally administered, once-daily CNS-penetrant sGC stimulator designed for the treatment of serious CNS diseases. A copy of the webinar presentation materials is attached hereto as Exhibit 99.2 and is incorporated by reference to this Current Report on Form 8-K. The presentation is also posted to the Company’s website, www.cyclerion.com.

The information set forth in and incorporated by reference into this Item 7.01 is being furnished pursuant to Item 7.01 of Form 8-K and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, and it shall not be deemed incorporated by reference in any filing under the Securities Act or under the Exchange Act, whether made before or after the date hereof, except as expressly provided by specific reference in such a filing.

By filing this Current Report on Form 8-K and furnishing the information in and incorporated by reference into this Item 7.01, the Company makes no admission as to the materiality of Item 7.01 in this report or the presentations available on the Company’s website. The information contained in the presentations is summary information that is intended to be considered in the context of the Company’s filings with the Securities and Exchange Commission (the “SEC”) and other public announcements that the Company makes, by press release or otherwise, from time to time. The Company undertakes no duty or obligation to publicly update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate or as required by applicable law. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases, by updating its website or through other public disclosure.

Item 9.01

Financial Statements and Exhibits

(d)

Exhibit No.		Description

99.1		Corporate Update Presentation dated July 9, 2020.
99.2		CNS Update Presentation dated July 9, 2020.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	Cyclerion Therapeutics, Inc.


Dated: July 9, 2020	By:	/s/ William Huyett
		Name:	William Huyett
		Title:	Chief Financial Officer

Exhibit 99.1

Delivering impact in CNS diseases Investor webinar July 9, 2020

Safe Harbor Statement This presentation contains forward - looking statements. Any statements contained in this presentation that are not historical fac ts may be deemed to be forward looking statements. Words such as “anticipate,” “believe,” “potential,” “expect,” “may,” “will,” “should,” “could,” “plan,” “estimate,” “target,” “project,” “contemplate,” “intend,” “future,” “will,” “predict,” “continue,” an d the negative of these terms and similar expressions are intended to identify these forward - looking statements. These forward - looking statements are based on Cyclerion’s current expectations, projections and trends, are only predictions and involve known and unknown risks and uncertainties that could cause actual results to differ materially from those expressed o r implied in such statements. Investors are cautioned not to place undue reliance on these forward - looking statements, which include but are not limited to statements about possible or assumed future results of operations; preclinical, clinical and n on - clinical studies, the interpretation of data therefrom and the ability to replicate findings from such studies; business stra teg ies, research and development plans, collaborations, partnerships, out - licensing (including without limitation with respect to praliciguat), regulatory activities and any timing thereof; competitive position, potential growth or commercial opportunitie s; the clinical potential, application, commercialization or potential markets of or for any proposed products; the anticipated timi ng of release of data from any clinical trials; and the size and design of those clinical trials. Applicable risks and uncertainties include those listed under the heading “Risk Factors” and elsewhere in our most recent For m 1 0 - K filed with the SEC on March 12, 2020, and in our subsequent SEC filings, including our Quarterly Report on Form 10 - Q filed wit h the SEC on May 4, 2020. These forward - looking statements speak only as of the date of this presentation, and we undertake no obligation and do not intend to update these forward - looking statements. 2

Two priority disease areas creating multiple potential ways to win in sickle cell and CNS • genetically and phenotypically defined populations with high unmet need • harness power, signaling precision of sGC • biomarker - guided fast - to - POC trials underway • supported by discovery platform • attractive to investors and partners Innovative sGC platform for the NO - sGC - cGMP pathway • multi - dimensional pharmacology well - suited to disease biology • molecules tailored to the tissues relevant to the disease • wholly owned IP • validated class Creating value from pioneering approaches to SCD and CNS Sickle Cell CNS Building a company: our sGC science, pipeline and our team 3

Clinical program snapshot 4 Ph1 (n=110 HV) SAD/MAD Ph 2a study: Alzheimer’s disease with vascular pathology (ADv) • safety/ tolerability in elderly subjects • PK • target and pathway engagement • pharmacodynamic biomarkers: CBF, cGMP December 2019 t op line expected late summer 2020 Ph1b translational pharmacology study Ph 2a study: MELAS safety/tolerability target engagement QD dosing CNS penetration Lessons inform iterative development strategy Ph2 STRONG - SCD study in SCD • safety, tolerability, PK • fit - for - purpose patient - reported outcomes (ePRO) instrument • pharmacodynamic effect: biomarkers (Hb, HbF, inflammation, adhesion) and daily symptoms Ph1 (n=86 HV) SAD/MAD safety/tolerability target engagement QD dosing t op line expected late Q3 2020 Ph 3 study: SCD Q2 2019 OLINCIGUAT (SCD) IW - 6463 (CNS)

Sickle Cell • potential for broad clinical utility in SCD • multi - dimensional mechanism that offers both upstream and downstream pharmacology • 70 patients enrolled; dosing completed • TL expected late Q3 2020 • Ph3 long - lead items underway: CMC, protocols, global ad board, regulatory plans • plan to develop and commercialize ourselves, but partnerships will be considered 5 Olinciguat: potential to raise the standard of care for sickle cell disease patients

• newly approved therapies each target a single clinical domain… • …olinciguat has the potential to improve four • daily symptoms and end - organ protection remain unaddressed, decreasing QoL and increasing mortality • further improvement in anemia and/or VOC possible with olinciguat alone or as add - on therapy serving broad SCD patient population 6 Potential for broad clinical utility improve daily symptoms olinciguat reduce anemia reduce painful crises (VOC) preserve organ function

OLINCIGUAT sGC stimulation may restore deficient nitric oxide signaling Increased hemolysis leads to reduced nitric oxide state Upstream • increased HbF may lead to reduced proportion of sickled RBCs 1 Downstream • improved blood flow • decreased vascular inflammation & cell adhesion • improved endothelial integrity 1. Conran, N., & Torres, L. (2019). cGMP modulation therapeutics for sickle cell disease. Experimental Biology and Medicine, 244 (2), 132 – 146. 7 Olinciguat: potential upstream and downstream interventions

1 2 3 4 * Decrease in progression of hemolytic anemia in Townes SCD mouse model Higher mRNA expression of the γ - globin subunit of fetal hemoglobin in cultured cells Olinciguat extended survival in TNF α challenge Berkeley SCD mouse model † Adhesion can occlude microcirculation and lead to painful VOC and other serious complications; 1. **** p<0.0001 vs TNF α - vehicle, 1h predose olinciguat followed by treatment with TNFα in normal mice; 2.*p<0.05; 3. **** p<0.0001 vs vehicle Treatment of K562 cells with vehicle or olinciguat for 7 days in cell culture, 4 * p<0.05 vs TNF α - vehicle, work done collaboratively with the laboratory of Paul Frenette (Albert Einstein), HU did not show benefit to survival 8 Preclinical data support clinical investigation Lower levels of vascular inflammatory markers and improved vascular function in mouse models of inflammation † INFLAMMATION ANEMIA FETAL HEMOGLOBIN SURVIVAL

1h predose olinciguat followed by treatment with TNF α in normal mice Lower expression of cellular adhesion molecules associated with olinciguat treatment in preclinical model † † in models of vascular inflammation, * p<0.05, ** p<0.001; **** p<0.0001 vs TNF α - vehicle 9

*p<0.05; ** p<0.01 Olinciguat vs Vehicle at Day 10 10 In a preclinical model of SCD, progression of hemolytic anemia was ameliorated in olinciguat treated Townes mice Red blood cell count Total hemoglobin Hematocrit

HbAAVeh Oli 0 100 200 300 400 s P - s e l e c t i n ( n g / m l ) HbSS *** * HbAAVeh Oli 0 50 100 150 200 s E - s e l e c t i n ( n g / m l ) HbSS *** * HbAAVeh Oli 0 2 4 6 8 10 12 I L - 6 p g / m L ** * HbSS HbAAVeh Oli 0 200 400 600 800 C y s t a t i n C ( n g / m l ) ** * HbSS HbAAVeh Oli 0.002 0.004 0.006 0.008 0.010 K i d n e y / B W ( g / g ) HbSS *** ** Endothelial Activation and Inflammation HbAAVeh Oli 0 50 100 150 200 N G A L ( n g / 2 4 h r s ) ** * HbSS Renal Injury *p<0.05, **p<0.01, ***p<0.001 11 Olinciguat decreased biomarkers of inflammation, endothelial activation and renal injury in Townes SCD mice after 8 weeks of treatment

Olinciguat Phase 1: target engagement, PK, safety, QD dosing Phase 1 design • 5 Ph1 studies including: - SAD - MAD - clinical pharmacology • 125 healthy volunteers • age range 18 - 57 • standard safety • PK • 8 dose levels tested • linear, predictable PK; consistent with QD dosing • determined well tolerated dose range • evidence of target engagement and proof of pharmacology (cGMP elevation, blood pressure) • well tolerated at all dose levels, no safety signals or discontinuations due to drug - related adverse events (AE) • balanced tissue: plasma distribution *Based on positive CNS pharmacology in multiple preclinical models Results PHASE 1 (completed) GOALS ACHIEVED 12

Structure • 70 patients enrolled in all SCD genotypes, aged 16 – 70 • placebo controlled, double blind • 4 dose levels • 12 - week treatment Objectives • assess safety and tolerability • confirm PK profile in SCD patients • development of the CYCN fit - for - purpose patient - reported outcomes (ePRO) instrument • signs of pharmacodynamic effect: biomarkers ( Hb, HbF , inflammation, adheion) and daily symptom effects Insights for Phase 3 design • endpoint selection based on results (biomarkers and ePRO) • determine study sample size and dose(s) Topline results expected late Q3 2020 Olinciguat phase 2 trial designed to support rapid advancement 13

• targeting the untapped NO neurotransmitter pathway by sGC stimulation • initial two indications are characterized by strong biological rationale, targeted patient populations, enormous unmet patient need, lack of approved therapies, and biomarker - based development • MELAS - genetically defined rare disease - most common mitochondrial disease, >90% have neurological symptoms (stroke - like episodes, dementia, epilepsy, vision loss) - identifiable patients with no approved treatment • Alzheimer's disease with vascular pathology (ADv) - intersection of Alzheimer’s and vascular dementias - well - defined subset of patients, ~2M patients in the US - no approved therapies to treat vascular pathology of Alzheimer's disease • discovery research engine focused on expanding CNS platform • exploring R&D collaboration to support pursuit of the best opportunities CNS 14 Our strategy: target identifiable populations with important unmet needs

clear biological rationale geno/ phenotypically defined populations • pursue multiple indications in parallel • leverage biomarkers to drive development • implement nimble trials with leading edge investigators and imaging analytics • investigate a strategic R&D partnership to explore full potential of sGC in the CNS Raising the odds of success: important patient need IW - 6463 Our approach: intersection of patients and biology 15

Nitric oxide • IW - 6463 GABAergic • Valium® (1963) • Ambien® (1992) Dopaminergic • Levodopa (1970) • Risperdal® (1993) Cholinergic • Scopolamine (1979) • Aricept® (1996) Adrenergic/Serotonergic • Amitriptyline (1961) • Prozac® (1987) • Paxil® (1992) Successfully drugged neurotransmitter systems Glutamatergic • Ketamine (1970) • Namenda® (2003) 16 sGC stimulators: potential to be next druggable neurotransmitter system

IW - 6463 demonstrates in preclinical studies beneficial effects in four important domains of neurodegenerative diseases Cellular Bioenergetics Increased ATP and restored gene expression in cells from patients with mitochondrial diseases Cerebral Blood Flow Increased blood flow in areas associated with memory and arousal by fMRI BOLD imaging Neuro - inflammation Decreased markers of LPS - induced neuroinflammation (ICAM1, VCAM1, IL6) in vitro Neuronal Function Enhanced memory performance & spine density in aged animals; increased LTP in neurodegenerative disease models ENHANCE IMPROVE REDUCE IMPROVE 17

IW - 6463 preclinical results support potential broad use in CNS treatment Cellular Bioenergetics Cerebral Blood Flow Neuro - inflammation Neuronal Function ENHANCE IMPROVE REDUCE IMPROVE Inflammatory cytokine in rat brain 3D microtissues V e h i c l e A M P K a c t i v a t o r F C C P ( 1 0M ) I W - 6 4 6 3 ( 0 . 1 M ) 0 100 200 300 ATP (pmole/ug protein) * ** Mitochondrial disease patient cells Maze performance in aged rats 18

Translational approach from discovery to approval and beyond • indication selection • patient selection • biomarker enrichment • endpoint selection • trial design • regulatory approach top line data late summer 2020 Establish PD biomarkers preclinically Effects across four domains of neurodegenerative disease Validate PD biomarkers in the clinic Translational pharmacology study in elderly Smaller/shorter studies Evaluate IW - 6463 in focused patient populations Initial approvals based on predictive surrogate and/or symptomatic and functional endpoints Larger/longer studies Evaluate IW - 6463’s full potential Potential to expand label to broader populations and to demonstrate disease modification Refine clinical strategy 19

Translational pharmacology study in elderly (ongoing) • safety • pharmacokinetics • target engagement • pharmacodynamic biomarkers Phase 1 (completed) • safety • pharmacokinetics • pharmacodynamics • target engagement • dose selection for next study Parallel exploratory Phase 2 studies • focused patient subsets • translational biomarker data • safety • pharmacokinetics • pharmacodynamics • early impact on disease Biomarker - driven IW - 6463 early clinical development strategy CNS exposure CNS activity CNS disease biomarker t op - line expected late summer 2020 Phase 1 studies conducted at Centre for Human Drug Research, Leiden, NL 20

IW - 6463 Phase 1: CNS exposure, target engagement, PK, and safety Study design • three stages: - SAD - MAD - food interaction • 110 healthy volunteers • age range 18 - 63 • standard safety • PK (blood & CSF) • wide dose range tested • identified safe and well - tolerated dose levels with steady - state CNS exposure in therapeutic target range* • linear, predictable PK; consistent with QD dosing • CNS exposure confirmed • evidence of target engagement (blood pressure) • well tolerated at all dose levels, no safety signals • may be taken with or without food *Based on positive CNS pharmacology in multiple preclinical models Results PHASE 1 (completed) GOALS ACHIEVED 21

Cellular Bioenergetics • brain metabolism via magnetic resonance spectroscopy (MRS) Cerebral Blood Flow • MRI arterial spin labeling (ASL ) Neuro - inflammation • cytokines, adhesion molecules Neuronal Function • qEEG • measures of cognition and behavior ( NeuroCart ®) ENHANCE IMPROVE REDUCE IMPROVE Assessing safety, PK and target engagement in CNS (cGMP) Top line data expected late summer 2020 24 elderly subjects IW - 6463 QD placebo 15 days 15 days IW - 6463 QD placebo washout 22 Translational study design: pharmacodynamic biomarkers and safety

MELAS: Strong supportive data for NO - sGC - cGMP pathway involvement Clinical precedence for NO - sGC - cGMP pathway • L - Arginine (NO precursor) recommended for acute and chronic treatment Pathophysiology • CNS metabolic dysfunction, elevated lactate, decreased NO • CNS vascular pathology - impaired blood flow, inflammation, endothelial dysfunction, small vessel disease IW - 6463 pharmacology • CYCN preclinical data suggest IW - 6463 improves mitochondrial function and cerebral blood flow SCIENTIFIC RATIONALE FOR INDICATION AND PATIENT SELECTION 23

Ph 2a: open - label study of IW - 6463 in patients with MELAS Enrichment strategy • genetically defined MELAS with neurological features and elevated plasma lactate (disease biomarker) Treatment • once - daily IW - 6463 • 29 days • up to 20 patients (targeting 12 completers) Sites • centers of excellence for mitochondrial diseases: CHOP, MGH, Children’s National, Columbia, Hopkins Objectives • evaluate safety, tolerability, and pharmacodynamics • assess near - term impact on disease - specific biomarkers • de - risk and accelerate future development DISEASE DOMAIN ASSESSMENT Mitochondrial dysfunction Lactate Dysregulated brain perfusion Cerebral Blood Flow (MRI ASL) Neurodegeneration NF - L Cognitive impairment Cognitive and behavior tests STUDY START Q3 2020 Improved lactate and CBF would indicate an impact on the underlying disease mechanism and suggest potential for broad benefit for these patients. 24

Alzheimer’s Vascular mixed dementia Pathophysiology NO dysregulation, endothelial cell loss, impaired blood flow, vascular leakage, inflammation, neuronal dysfunction, and neuronal loss are major contributing factors to rapid disease progression Standard of care No approved therapies to treat vascular dementia. AD therapies offer limited benefits; not disease modifying Pharmacology Our preclinical data suggests IW - 6463 has potential to improve cerebral blood flow, endothelial health, neuroinflammation, and cellular energetics as well as prevent neurodegeneration Alzheimer’s Association,, Rizzi et al., NCI Analysis Target population ADv : an identifiable subset of mixed dementia patients with: • AD pathology AND • sub - cortical vascular disease AND • CV risk factors ADv AD with vascular pathology (ADv) – focused mixed dementia subset Defined population well suited for treatment with IW - 6463 DISEASE RATIONALE FOR PATIENT SELECTION 25

Treatment • once - daily IW - 6463 Enrichment strategy • confirmed AD pathology (PET, CSF) • 3+ cardiovascular risk factors • mild - moderate subcortical small - vessel disease on MRI • mini Mental State Exam score (16 - 26) Objectives • establish safety and pharmacodynamic effects of IW - 6463 in a short - term study • de - risk progression to larger, longer symptomatic and disease modification trials Vascular dysfunction ASL (CBF) Neurodegeneration neurofilament light chain Neuroinflammation vascular cell adhesion molecule Mitochondrial dysfunction N - acetyl aspartate (MRS) Cognitive impairment cognitive and behavior tests STUDY START 1H 2021 DISEASE DOMAIN ASSESSMENT Ph 2a study of IW - 6463 in ADv: emerging design Improved CBF, particularly in the context of memory improvements, would indicate an impact on the underlying disease mechanism and enable a targeted design for the next development stage. 26

• sGC stimulators: powerful intervention in a genetically and clinically validated pathway • a wholly owned pipeline of differentiated molecules • exploring partnerships across programs; praliciguat out - licensing scope expanded • experienced leadership team with a distinctive track record of innovative drug discovery and development • starting Q3 2020 with ~$61M cash*; supports our priorities into second half of 2021 • limited disruption from Covid - 19 Sickle Cell CNS * Preliminary, unaudited unrestricted cash, cash equivalents and restricted cash balance as of June 3o, 2020 27 Building our company: the science, the pipeline and the team Building a company: our sGC science, pipeline and our team

• multiple successful drugs target the NO - sGC - cGMP pathway for the treatment of CV diseases NO donors, PDE5 inhibitors, sGC stimulators • NO - sGC - cGMP pathway plays central role in CNS diseases Network analysis delivers z - scores for CNS diseases similar to validated CV diseases • sGC: optimal target for pathway intervention Broadly expressed in CNS, amplifies endogenous signaling, increases cGMP levels at the source with no attenuation of response Therapeutic effects PDE sGC stimulators: ideal intervention in a genetically and clinically validated pathway 28

SMOOTH MUSCLE & VASCULAR FUNCTION METABOLISM CELLULAR BIOENERGETICS NEURONAL FUNCTION INFLAMMATION 29 Broad impact in the NO - sGC - cGMP pathway

30 sGC stimulators are positive allosteric modulators that enhance NO - sGC - cGMP signaling

Liver - targeted Lung - targeted Preclinical Olinciguat Phase 2 proof - of - concept study in sickle cell disease ongoing (SCD) Topline data expected late Q3 2020 Praliciguat Results support out - license for further development IW - 6463 Phase 1 completed, with good CNS exposure, once - daily oral PK, and good safety/tolerability. Translational pharmacology study dosing completed; top line data expected late summer 2020 Anticipate launching two exploratory Phase 2 studies Ongoing Clinical Programs Completed Clinical POC 31 A wholly owned pipeline of differentiated molecules

• promising DN results: - UACR reductions on top of standard of care - reductions in blood pressure, HbA1c, total and LDL cholesterol - favorable safety profile, consistent with previous studies - attractive dosing and PK relative to others in class • VICTORIA results further validate cardiometabolic potential of the class and suggest potential for praliciguat as a cardio metabolic therapeutic Out - licensing discussions ongoing Data support further development • continuing discussions to out - license global rights to praliciguat • expanded the scope of its out - licensing discussions beyond cardiometabolic disorders to include additional indications where sGC stimulators have shown efficacy • no assurances on the prospects or timing of any partnership or licensing transactions -- generally or specifically on praliciguat 32 Praliciguat out - licensing discussions ongoing with expanded scope

• distinctive track record of innovative drug discovery/development (e.g. -- CELEBREX ® , KALYDECO ® , LINZESS ® , LUNESTA ® , OPDIVO ® , ORKAMBI ® , YERVOY ® ) • successful sGC/cGMP drug hunters; deep knowledge of nitric oxide (NO) - cGMP pathway • broad experience in creating strong organizations and commercializing products Experienced team and successful leadership 33

Delivering impact in CNS diseases Investor webinar July 9, 2020

Exhibit 99.2

Delivering impact in CNS diseases Investor webinar July 9, 2020 V7

Peter Hecht, PhD Chief Executive Officer Welcome to Cyclerion’s CNS discussion Marni J. Falk, M.D. University of Pennsylvania Professor of Human Genetics; The Children's Hospital of Philadelphia (CHOP), Director of the Mitochondrial Medicine Frontier Program Cheryl Gault Head of Strategy & Corporate Development Mark Currie, PhD President and Chief Scientific Officer Andy Busch, PhD Chief Innovation Officer Christopher Wright, MD, PhD Chief Medical Officer Christopher Winrow, PhD Senior Director, Clinical Development – Neuroscience Program Lead Eric E. Smith, MD, MPH, FRCPC, FAHA University of Calgary Professor of Neurology Katthy Taylor Chair in Vascular Dementia, Cumming School of Medicine 3 CYCLERION LEADERS INDEPENDENT EXPERTS

Pioneering therapeutics in SCD and CNS Sickle Cell Disease (SCD) • upstream + downstream pharmacology • 70 patients enrolled; dosing completed • top line expected end Q3 2020 Central Nervous System (CNS) • potential to be next druggable neurotransmitter system • IW - 6463: oral, QD drug • first CNS - penetrant sGC stimulator in development • top line expected end of summer 2020 4

Objectives for today How Cyclerion can create value in CNS Discuss the broad therapeutic potential of sGC stimulators in CNS Describe the rich yield of data and its implications (data due late summer) Discuss our first indications: focused patient populations, biomarker - based development Now is the time: value in CNS sGC and CNS: scientific and clinical basis for CNS therapies Translational pharmacology study: demonstrating CNS activity Clinical direction in CNS: important indications that yield early answers 1 2 3 4 6

Cyclerion: delivering impact in CNS Now is the time: value in CNS sGC and CNS: scientific and clinical basis for CNS therapies Translational pharmacology study: demonstrating CNS activity Clinical direction in CNS: important indications that yield early answers 1 2 3 4 • growing patient populations and evolving science creates opportunity • we believe our approach can raise the odds of success • translational pharmacology data (due late summer) are expected to demonstrate CNS activity 7

Capturing potential in a high reward therapeutic area • rapidly growing patient population, lack of approved therapies, important unmet need • quickly evolving science: genetic insights and technologies • valued by investors and industry partners • Cyclerion is the innovator of sGC in the CNS Now is the time We’ve learned from industry history • understanding disease biology is critically important • adequate CNS exposure is essential • identifying translational CNS biomarkers is key 8

IW - 6463 biomarker - guided development in focused patient populations P h1 (n=110 HV) SAD/MAD Ph 2a study: Alzheimer’s disease with vascular pathology (ADv) • safety/ tolerability in elderly subjects • PK • target and pathway engagement • pharmacodynamic biomarkers: CBF, cGMP December 2019 top line data expected late summer 2020 Ph1b translational pharmacology study Ph 2a study: MELAS with CNS symptoms safety/tolerability target engagement CNS penetration Learnings inform iterative development strategy 10

sGC and CNS: scientific and clinical basis for CNS therapies Now is the time: value in CNS sGC and CNS: scientific and clinical basis for CNS therapies Translational pharmacology study: demonstrating CNS activity Clinical direction in CNS: important indications that yield early answers 1 2 3 4 • sGC stimulators are clinically validated in several diseases • sGC /NO pathway identified as drug target for CNS diseases using systems biology approach • IW - 6463 active in four domains: cerebral blood flow, cellular bioenergetics, neuro - inflammation, neuronal function 11

Multiple successful drugs target the NO - sGC - cGMP pathway for the treatment of CV diseases NO donors, PDE5 inhibitors, sGC stimulators NO - sGC - cGMP pathway plays central role in CNS diseases Network analysis delivers z - scores for CNS diseases similar to validated CV diseases sGC: optimal target for pathway intervention Broadly expressed in CNS, amplifies endogenous signaling, increases cGMP levels at the source with no attenuation of response Therapeutic effects PDE sGC stimulators: ideal intervention in a genetically and clinically validated pathway 12

Growing appreciation of the role of NO - sGC - cGMP pathway in CNS disease sGC: a central regulator of brain physiology SMOOTH MUSCLE & VASCULAR FUNCTION METABOLISM CELLULAR BIOENERGETICS NEURONAL FUNCTION INFLAMMATION 13

sGC stimulators: potential to be next druggable neurotransmitter system Nitric oxide • IW - 6463 GABAergic • Valium® (1963) • Ambien® (1992) Dopaminergic • Levodopa (1970) • Risperdal® (1993) Cholinergic • Scopolamine (1979) • Aricept® (1996) Adrenergic/Serotonergic • Amitriptyline (1961) • Prozac® (1987) • Paxil® (1992) Successfully drugged neurotransmitter systems Glutamatergic • Ketamine (1970) • Namenda® (2003) 14

15 NO - sGC - cGMP pathway: From validated cardiometabolic diseases to CNS disease validation Disease genetics network NO - sGC - cGMP pathway Human interactome x Network analysis reveals disease linkage Z - score CNS Diseases • Alzheimer’s disease • cognitive impairment • stroke • bipolar disorder • schizophrenia • depression • Huntington’s disease Cardiometabolic Diseases • hypertension* • diabetic nephropathy* • heart failure* • arteriosclerosis • diabetes* • PAH* • sickle cell anemia * sGC stimulator(s) with clinical effects

Attractive nonclinical profile supports clinical development • IW - 6463 demonstrates pharmacological activity across four distinct domains in multiple preclinical models • preclinical results support straightforward translation into the clinic • CNS exposure and target engagement demonstrated in multiple species • no evidence of CYP enzyme inhibition and IW - 6463 not a P - gp substrate • nonclinical toxicology profile consistent with other sGC stimulators in development Advance to clinical development 17

Translational pharmacology study: confirming CNS activity Now is the time: value in CNS sGC and CNS: scientific and clinical basis for CNS therapies Translational pharmacology study: demonstrating CNS activity Clinical direction in CNS: important indications that yield early answers 1 2 3 4 • rational indication selection approach for CNS diseases • phase 1 GO – identified well - tolerated doses achieving the desired CNS exposure • elderly translational pharmacology study focused on CNS target engagement (late summer) 18

Translational pharmacology study in elderly (ongoing) • safety • pharmacokinetics • target engagement • pharmacodynamic biomarkers Phase 1 (completed) • safety • pharmacokinetics • pharmacodynamics • target engagement • dose selection for next study Parallel exploratory Phase 2 studies • focused patient subsets • translational biomarker data • safety • pharmacokinetics • pharmacodynamics • early impact on disease Biomarker - driven IW - 6463 early clinical development strategy CNS exposure CNS activity CNS disease biomarker top line data expected late summer 2020 Phase 1 studies conducted at Centre for Human Drug Research, Leiden, NL 19

Translational study design: pharmacodynamic biomarkers and safety 21 Cellular Bioenergetics • brain metabolism via magnetic resonance spectroscopy (MRS) Cerebral Blood Flow • MRI arterial spin labeling (ASL ) Neuro - inflammation • cytokines, adhesion molecules Neuronal Function • qEEG • measures of cognition and behavior ( NeuroCart ®) ENHANCE IMPROVE REDUCE IMPROVE Assessing safety, PK and target engagement in CNS (cGMP) Top line data expected late summer 2020 24 elderly subjects IW - 6463 QD placebo 15 days 15 days IW - 6463 QD placebo washout 21

Translational approach from discovery to approval and beyond • indication selection • patient selection • biomarker enrichment • endpoint selection • trial design • regulatory approach Top line data late summer 2020 Establish PD biomarkers preclinically Effects across four domains of neurodegenerative disease Validate PD biomarkers in the clinic Translational pharmacology study in elderly Smaller/shorter studies Evaluate IW - 6463 in focused patient populations Initial approvals based on predictive surrogate and/or symptomatic and functional endpoints Larger/longer studies Evaluate IW - 6463’s full potential Potential to expand label to broader populations and to demonstrate disease modification Refine clinical strategy 22

Clinical direction in CNS: important indications that yield early answers Now is the time: value in CNS sGC and CNS: scientific and clinical basis for CNS therapies Translational pharmacology study: demonstrating CNS activity Clinical direction in CNS: important indications that yield early answers 1 2 3 4 • MELAS and ADv trials designed to uncover meaningful CNS biomarker engagement • approach efficiently de - risks & allows quick progression to the next development stages 23

Central Nervous system Strokes, Stroke - like Episodes (SLEs), Ataxia (Imbalance), Epilepsy (Seizures), Migraine, Headaches, Cognitive Impairment, Learning Disability, Dementia, Mood disorders Skeletal muscle Muscle weakness, myopathy, exercise intolerance Mitochondrial Encephalomyopathy , Lactic Acidosis,& Stroke - like Episodes (MELAS) genetically defined orphan disease, serious CNS & multi - system problems, no approved treatments Peripheral Nervous System Peripheral Neuropathy Autonomic Nervous System Dysautonomia, Temperature Intolerance, Heart Rate Instability (POTS) Endocrine/Metabolic Diabetes Mellitus, Short Stature, Underweight, Fatigue, Lactic Acidosis Hearing Sensorineural Hearing Loss, Tinnitus Cardiac Sudden Death, Arrhythmias, Cardiomyopathy Gastrointestinal Vomiting, Pseudoobstruction Vision Vision Loss, Cortical Blindness, Ptosis, Ophthalmoplegia, Retinal - Optic Nerve Disease Renal Nephropathy SYMPTOM OVERVIEW stroke 24

~80% experience cerebellar ataxia, sensorineural hearing loss, ophthalmologic problems, neuropathies Almost all patients present with neurologic symptoms such as stroke and developmental disabilities Almost all patients exhibit neurological manifestations, including hypotonia, epilepsy, ataxia, etc. Prevalence of neurological symptoms ranges from 40% to 70% for each and includes ataxia, epilepsy, vision loss, etc. 40 - 50% (~30K) of total PMD patients are 16 years or older Of the 4 target diseases, 55 - 65% (~25K) fall into this age category due to both later diagnosis and longer life expectancy ~50K PMD patients exhibit CNS symptoms Kearns - Sayre Syndrome Mitochondrial Depletion Syndromes Other Presentations Leigh Syndrome Primary Mitochondrial Disease (PMD) prevalence is 1 in 4,300 individuals = US case estimate ~65K ≥ 90% who present with classical MELAS have stroke - like episodes, dementia, epilepsy, vision loss MELAS Focused MELAS trial population for trials; potential for broader use US prevalence of mitochondrial disease and CNS symptoms 25 See citations in the appendix

Potential therapeutic benefit of IW - 6463 Impaired mitochondrial energy production IW - 6463: potentially impacts MELAS pathophysiology at multiple points Impact of L - Arginine/citrulline treatment Mutation leading to decreased protein synthesis Decreased citrulline & arginine synthesis Mitochondrial proliferation Angiopathy & endothelial dysfunction Impaired perfusion in microvasculature Decreased NO synthesis Nitric oxide deficiency Multi - organ dysfunction Oxidative stress Increased ADMA Decrease NOS activity Increased RNS See citations in the appendix 26

MELAS: strong supportive data for NO - sGC - cGMP pathway involvement Clinical precedence for NO - sGC - cGMP pathway • L - Arginine (NO precursor) recommended for acute and chronic treatment Pathophysiology • CNS metabolic dysfunction, elevated lactate, decreased NO • CNS vascular pathology - impaired blood flow, inflammation, endothelial dysfunction, small vessel disease IW - 6463 pharmacology • CYCN preclinical data suggest IW - 6463 improves mitochondrial function and cerebral blood flow SCIENTIFIC RATIONALE FOR INDICATION AND PATIENT SELECTION 27

Ph 2a: open - label study of IW - 6463 in patients with MELAS Enrichment strategy • genetically defined MELAS with neurological features and elevated plasma lactate (disease biomarker) Treatment • once - daily IW - 6463 • 29 days • up to 20 adults (targeting 12 completers) Sites • centers of excellence for mitochondrial diseases: CHOP, MGH, Children’s National, Columbia, Hopkins Objectives • evaluate safety, tolerability, and pharmacodynamics • assess near - term impact on disease - specific biomarkers • de - risk and accelerate future development DISEASE DOMAIN ASSESSMENT Mitochondrial dysfunction Lactate Dysregulated brain perfusion Cerebral Blood Flow (MRI ASL) Neurodegeneration NF - L Cognitive impairment Cognitive and behavior tests STUDY START 2H 2020 Improved lactate and CBF would indicate an impact on the underlying disease mechanism and suggest potential for broad benefit for these patients. 28

• AD & vascular dementia - two most common dementias • pure forms exist, but vascular pathology widely prevalent in AD • mixed dementia = broad area of overlap • subcortical small vessel disease (SVD) in a significant portion • mixed dementia patients more rapidly progressive disease, higher symptom severity • ~2M US patients; incidence increasing with aging • symptomatic treatment for AD – modest, brief benefit • no disease - modifying therapies, none targeting the vasculature Alzheimer’s Disease Vascular Dementia Mixed Dementia Dementia type Pathophysiology Alzheimer’s • neurofibrillary tangles • amyloid plaques Vascular • impaired brain blood flow Mixed Dementia • combination of the above PATIENT PRESENTATION & CHARACTERISTICS UNMET NEED Vascular pathology in dementia – clinical perspective SVD AD 29

Vascular pathology: a key contributor to dementia Adapted from Faraco and Iadecola (2013) Hypertension 62:810 • risk factors and common comorbidities : DM, HTN, HL, Smoking, CAD • ApoE risk partly mediated by endothelial dysfunction and BBB breakdown • brain ischemic changes present in dementia, including AD; possibly independent disease progression risk factor • vasculature implicated in a - beta brain clearance, a process that fails in AD SUPPORTIVE EVIDENCE See citations in the appendix 30

Alzheimer’s Vascular mixed dementia Pathophysiology NO dysregulation, endothelial cell loss, impaired blood flow, vascular leakage, inflammation, neuronal dysfunction, and neuronal loss are major contributing factors to rapid disease progression Standard of care No approved therapies to treat vascular dementia. AD therapies offer limited benefits; not disease modifying Pharmacology Our preclinical data suggest IW - 6463 has potential to improve cerebral blood flow, endothelial health, neuroinflammation, and cellular energetics as well as prevent neurodegeneration Alzheimer’s Association,, Rizzi et al., NCI Analysis Target population ADv : an identifiable subset of mixed dementia patients with: • AD pathology AND • sub - cortical vascular disease AND • CV risk factors ADv AD with vascular pathology (ADv) – focused mixed dementia subset Defined population well suited for treatment with IW - 6463 DISEASE RATIONALE FOR PATIENT SELECTION 31

Current Immediate Execution • pioneer understanding of powerful pharmacology • IW - 6463 MELAS study • IW - 6463 ADv study • explore partnership Long - term Portfolio Growth • commercialization • diversified portfolio • robust series of clinical catalysts • partnership(s) 33 Mid - term Portfolio Advancement • IW - 6463 late stage dev • IW - 6463 additional POCs • expanded CNS sGC portfolio • explore additional targets/assets • partnership(s) Committed to building CNS as a core therapeutic area

Thank you for joining • powerful platform for potential CNS therapies • adaptive, risk - reducing, development approach • seasoned drug development leaders with specialized scientific advisors • multiple ways to win: SCD and CNS • ownership base of long - term investors and employees 34

Questions 35

Delivering impact in CNS diseases Investor webinar July 9, 2020 V7

Citations Page Topic Citation 25 MELAS epidemiolgy Sources: 1. J Neurol. 2016; 263: 179 – 191; US population estimated at 327.2 million;2. Brain. 2003; 126(5): 1231 – 1240; 3. NIH Genetics Home Reference; 4. NCBI GeneReviews; 5. Neurotherapeutics. 2013 Apr; 10(2): 186 – 198 26 MELAS MOA El - Hattab, AW et al, 2016 30 Vascular pathology • Smith and Markus. New Treatment Approaches to Modify the Course of Cerebral Small Vessel Diseases (Stroke. 2020;51). • Bakker, Erik NTP et al. Lymphatic clearance of the brain; perivascular, paravascular and significance for neurodegenerative diseases. Cell Molec Neurobiol 36.2 (2016): 181 - 194. • Venturelli, Ben Aisa et al, (Cur Med Chem, 2016, 23, 2770 - 2788. Targeting NO/cGMP Signaling in the CNS for Neurodegeneration and Alzheimer’s Disease). • Montagne et al, (Nature, 581, 7 May 2020. APOE4 leads to blood - brain barrier dysfunction predicting cognitive decline). • Iadecola C et al. (Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019;73(25):3326 - 44.). • Coutu JP, et al. (Two distinct classes of degenerative change are independently linked to clinical progression in mild cognitive impairment. Neurobiol Aging. 2017; 54:1 - 9.). 37