Safe Harbor Statement This overview contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, such as statements about the status, structure and timing of our separation from Ironwood; expected timing of clinical data and the filing CTA/IND applications; the size and design of clinical trials; the application of; and potential benefits of sGC stimulators, our strategy, including development and commercialization plans; the size of potential markets for our product candidates and; our expected use of cash. 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 statements. Applicable risks and uncertainties include those related to our lack of independent operating history; the risk that a separation from Ironwood may adversely impact our ability to attract or retain key personnel; the effectiveness of our development and commercialization efforts; risks generally associated with preclinical and clinical development and formulation development; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; risks and uncertainties pertaining to the efficacy, safety and tolerability of our product candidates; decisions by regulatory authorities; the risk that we may never get sufficient patent protection for our product candidates or that we might not able to successfully protect such patents; the risks listed under the heading “Risk Factors” and elsewhere in Ironwood’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018 and in Ironwood’s subsequent SEC filings, including SEC filings related to the proposed separation. These forward-looking statements speak only as of the date of this overview, and Ironwood undertakes no obligation to update these forward-looking statements. This overview describes the businesses to be transferred to Cyclerion by Ironwood in the separation as if the transferred businesses were Cyclerion’s businesses for all historical periods described. References in this overview to Cyclerion’s historical assets, liabilities, product candidates, businesses or activities of Cyclerion’s business are generally intended to refer to the historical assets, liabilities, product candidates, businesses or activities of the transferred businesses as the businesses were conducted as part of Ironwood prior to the separation. 2

5 programs: on track to deliver 4 clinical data readouts in 2019 including 3 Phase 2 studies, and 2 new drug candidates Distinctive pharmacology: differentiated, tissue-targeted compounds tailored for intended diseases Powerful pathway: nitric oxide-sGC pathway is clinically validated with significant untapped potential Successful sGC/cGMP drug hunters: deep pathway knowledge with record of drug making success High-momentum company launch 3

4 clinical data readouts in 2019 on differentiated compounds - Top line data expected in 2H2019 Olinciguat Sickle Cell Disease (SCD) - Granted Orphan Drug Designation by the US FDA - Worldwide rights - DN: Top line data expected in 2H2019 Diabetic Nephropathy (DN) - HFpEF: Top line data expected in 2H2019 - Pursue out-licensing after completion of Phase 2 studies - Granted Fast Track Designation for HFpEF by the US FDA Praliciguat Heart Failure with Preserved Ejection Fraction (HFpEF) - Worldwide rights - CTA filed in 4Q2018 - Expect to initiate Phase I study 1Q2019 - Top line data expected in 2HQ2019 - Worldwide rights IW-6463 Serious + Orphan CNS Diseases Liver - Development candidate nomination expected Serious + Orphan Liver Diseases in 1H2019 - Development candidate nomination expected Lung Serious + Orphan Pulmonary Diseases in 1H2019 5 * Status of programs as of January 7, 2019. Represents ongoing phase of development and does not correspond to the completion of a particular phase. Lung-Targeted sGC Stimulator Liver-Targeted sGC Stimulator Central Nervous System sGC Stimulator Systemic sGC Stimulator Product*DiscoveryIND EnablingPhase 1Phase 2Phase 3Status and Anticipated Next Milestones Vascular sGC Stimulator

Tailoring proven, powerful serious diseases pharmacology for treatment of …that Cyclerion is working to harness A powerful pathway… • • Growing understanding of NO pathway role in health and disease Developing differentiated next-generation sGC stimulators uniquely designed to target tissues relevant to the diseases each is intended to treat Relevant in diseases both with and without nitric oxide signaling deficiency Fortified by deep expertise and IP in sGC stimulation Nitric oxide (NO) signaling plays a central role in real-time physiologic regulation of diverse systems Discovery of NO signaling was basis for the 1998 Nobel Prize in Physiology or Medicine Clinically validated by approved therapies (NO donors, PDE5 inhibitors, sGC stimulator) • • • • • 6

NO-cGMP signaling regulates multiple aspects of physiology sGC stimulators: differentiated mechanism to modulate NO-cGMP pathway signaling: • Act synergistically with the NO signaling system: same time and same locations in body vs. acting independently of NO signaling Increase overall pathway signaling vs. relying on basal signaling Act at a non-redundant node in the pathway and can act anywhere sGC is expressed to increase cGMP vs. inactivating just one of several mechanisms by which cGMP is degraded Selectively modulate NO signaling vs. acting across any pathway that increases cGMP • • • Adapted from Buys et al. 2018. Discovery and development of next generation sGC stimulators with diverse multidimensional pharmacology and broad therapeutic potential. Nitric Oxide 78:72-80 8

sGC stimulators act synergistically with NO In vitro (HEK293 cells) In vivo (rat liver/retrodialysis) 800 30 **** 600 20 400 ** * 10 200 * 0 0 -1 1 -1 0 -9 -8 - 7 - 6 -5 -4 PB S N O d o n o r S tim S tim + N O d o n o r l o g [ s t i m u l a t o r ] * p<0.05, *** p<0.001; **** p<0.0001 vs PBS 9 c G M P (n M ) c G M P (n M ) Stimulator + NO donor EC50 ~ 100 nM Stimulator alone EC50 ~ 3 µM

NO-sGC-cGMP signaling acts through multiple downstream pathways to elicit pharmacological effects sec STIMULATOR sGC Stimulation Can Increase I Local vasodilation I blood flow (e.g.,vascular and smooth muscle relaxation) Cyclic Nucleotide Gated Channels Metabolism (e.g., AMPK activation) Neuronal health and signaling (e.g., neuroprotection. LTP) GTP Protein Kinase G • sGC Stimulation Can Decrease Phosphodiesterases Inflammation (e.g., TNFa signaling, EC activation) I Fibrosis (e.g., TGFI3 signaling) 10

OLINCIGUAT Olinciguat: sickle Significant potential in cell disease (SCD) Potential to treat SCD by reducing proportion of sickled cells, decreasing vascular inflammation and cell adhesion, and improving local blood flow SCD is an orphan disease characterized by a low NO state, with early mortality, serious morbidity and limited number of treatment options Olinciguat is an oral, once-daily sGC stimulator that distributes to vasculature and highly perfused organs Preclinically, olinciguat treatment was associated with positive effects on blood flow and vascular inflammation Phase 2 STRONG SCD study is ongoing to evaluate safety, PK, PD and develop PRO instrument in patients with SCD; topline data expected 2H2019 13

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Sickle cell disease: the need SCD results in severe complications that may include painful vaso-occlusive crises ( VOCs), daily symptoms such as chronic pain, fatigue and shortness of breath, as well as progressive damage to organs, including the brain, kidneys, lungs, bones and cardiovascular system High morbidity and decreased QoL SCD patients ~100,000 in U.S.1 ~50,000 in EU52 Patients with SCD have a shortened life expectancy, with an average of 42 years for males and 48 years for females in the US Decreased life expectancy 14 1) Iughetti et al. Novel Insights in the Management of Sickle Cell Disease in Childhood.” World Journal of Clinical Pediatrics 2016. 2) France, Germany, Italy, Spain and the United Kingdom, Landscape & Forecast: Sickle Cell Disease. Decision Resources Group, October 2018

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Sickle cell disease: the nitric oxide connection Increased hemolysis leads to reduced NO Low NO bioavailability results in reduced Reduced cGMP leads to vasoconstriction, These effects contribute the symptoms and bioavailability and cGMP production vascular inflammation, and endothelial dysfunction complications of SCD in patients production These combined effects result in accumulated vascular and tissue damage that can lead to pain, organ failure, and shortened life expectancy

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED In preclinical models, olinciguat treatment was associated with positive effects on SCD pathology • Preclinically olinciguat treatment was associated with: - - Distribution to both the vasculature as well as key organs Higher mRNA expression of the -globin subunit of fetal hemoglobin in cultured cells Lower levels of vascular inflammatory markers and improved vascular function in mouse models of inflammation* Decrease in progression of hemolytic anemia in SCD mouse model - - 17 *Adhesion can occlude microcirculation and lead to painful VOC and other serious complications

OLINCIGUAT PRALICIGUAT LIVER-TARGETED LUNG-TARGETED I Lower expression of cellular adhesion molecules preclinical model associated with olinciguat treatment s-lselectin in sP-selectin 600 :r 500 E 01,: 400 :a 300 (.J "* 200 **** !{' 100 I 0 Naive Vehicle Olinciguat Naive Vehicle Olinciguat TNFa I TNFa sE-selectin siCAM1 1400 1200 ? 1000 ]: 800 200 :r ..§ 150 -1: Cl :a 100 i 600 400 200 0 (.J ..9! **** Q) w(/) 50 (/) (/) 0 Naive Vehicle Olinciguat TNFu Naive Vehicle Olinciguat TNFa 1h predose olinciguatfollowed by treatment with TNFa in normal mice **** **** * - **

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Olinciguat is progressing through clinical development • Completed Phase 1 studies in healthy subjects - - - Confirmed target engagement and proof of pharmacology Dose-proportional pharmacokinetics with profile supportive of once-daily dosing Well-tolerated dose range with no serious adverse events or discontinuations due to adverse events (AE) • • Granted Orphan Drug Designation for the treatment of sickle cell disease Initiated Phase 2 study in sickle cell disease; data expected 2H2019 20

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED STRONG SCD: Phase 2 ongoing, topline data expected 2H 2019 Ongoing Phase 2 Study Placebo Olinciguat Low dose Olinciguat Mid dose Olinciguat High dose QD, 12 WEEK TREATMENT PERIOD ENDPOINTS: • Safety, tolerability, pharmacokinetics, pharmacodynamics • Exploratory endpoints to enable decision making include: • Biomarkers of disease activity (HbF levels, anemia, inflammatory markers) • Health-related patient-reported outcomes (PRO) including chronic pain and fatigue PATIENTS: • Male and female patients with SCD, age 16 – 70 years • Maintain stable regimen of current medications for SCD • ~88 patients total Phase 2 study, data expected 2H 2019 21

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Pralicigu ca t has significant potential in dio metabolic dise se Positive effects on metabolic parameters, fibrosis, inflammation and renal and cardiac function in preclinical disease models. Metabolic effects demonstrated clinically Well suited for potential treatment of DN and HFpEF by reducing inflammation and fibrosis and enhancing blood flow to relevant tissues Phase 2 studies in HFpEF and DN are ongoing with 2H 2019 readouts, actively pursuing a global partnership to maximize value for patients and shareholders Oral, once-daily sGC stimulator with extensive distribution to key target tissues including kidney, heart, liver, and adipose tissue in preclinical models DN and HFpEF are serious cardiometabolic diseases with high morbidity and mortality; limited / no treatment options 22

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Diabetic nephropathy: the need In patients with diabetes, nephropathy is a major risk factor for cardiovascular disease, the major driver of excess cardiovascular mortality, and the single strongest predictor of mortality Significant unmet medical need DN is progressive, and patients that survive to end-stage renal disease require chronic dialysis treatment or kidney transplant There are over 400 million adults with diabetes globally at a prevalence rate of 8.5% Up to 40% of all patients with diabetes have DN Large patient population 23 1) Ghaderian SB, et al., Diabetes and End-Stage Renal Disease; A Review Article on New Concepts, J Renal Inj Prev. 2015; 2) https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease 3) Gheith et al., Diabetic Kidney Disease: world wide difference of prevalence and risk factors, Journal of Nephropharmacology 2016

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Diabetic nephropathy: the nitric oxide connection Diabetes is associated with endothelial dysfunction and reduced NO signaling1 Defects in NO signaling genetically linked to diabetic nephropathy2 NO signaling plays a central role in renal physiology The decrease in nitric oxide signaling is associated with the progression of DN 1) Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T, et al. Nature Reviews Nephrology. 2011; Cheng H, Harris RC. Cardiovascular & Hematological Disorders Drug Targets, 2014; 2) Dellamea, et al, BMC Med Genet 2014 3Krishnan, et al, Int J Mol Sci, 2018

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Preclinical and clinical data for praliciguat utility in diabetic nephropathy support potential Praliciguat treatment preclinically was associated with: • Preservation of kidney function in multiple animal models*, including corresponding effects on inflammation, fibrosis, and metabolism Anti-inflammatory and anti-fibrotic effects in vivo, mechanistically separated from hemodynamic pharmacology Positive effects on fasting glucose and lipids in ZSF1 rat model of diabetic nephropathy • • Praliciguat treatment clinically was associated with: • Decreases in insulin sensitivity and in plasma LDL cholesterol and triglycerides in Phase 2 study in patients with T2DM and hypertension on standard of care including anti-glycemic medications and RAAS inhibitor 26 * Dahl salt-sensitive rat model of hypertension and ZSF1 rat model of DN

OLINCIGUAT PRALICIGUAT LIVER-TARGETED LUNG-TARGETED Anti-fibrotic effects recapitulated in vitro and mechanistically separated from hemodynamic effects TGF -induced apoptosis 120• -100• - 80 .!a60 I tJ> 0 Q. 40 0 20 0 -20 Vehicle Vehicle Praliciguat TGF I • Human renal proximal tubule epithelial cells in cell culture { ' clerion ''·1''\ *** **** p<o.oo1; p<o.oo01vs TGF -veh1cle • • • • *** **** I •

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Praliciguat is progressing through clinical development • Completed Phase 1 studies in healthy subjects - - - Confirmed target engagement and proof of pharmacology Dose-proportional pharmacokinetics with profile supportive of once-daily dosing Demonstrated large volume of distribution and negligible renal clearance • Completed exploratory Phase 2 studies in patients with T2DM and a history of hypertension - - Pharmacokinetic/pharmacodynamic profile supportive of once-daily dosing Positive metabolic effects in a relevant patient population - Patients on standard of care including anti-glycemic medications and RAAS inhibitor - Dosing generally well tolerated; AEs reported in more than 2 patients were mild in severity; one SAE (upper GI hemorrhage) in a patient who had ulcerative esophagitis and previously undiagnosed hiatal hernia, resolved same day and patient recovered completely • FDA Fast Track Designation granted for HFpEF • Initiated Phase 2 POC studies in DN and in HFpEF; data expected from both in 2H 2019

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED DN Phase 2 trial ongoing, topline data expected 2H 2019 Ongoing Phase 2 Study Low dose High dose 12 WEEK TREATMENT PERIOD PATIENTS: Adult patients with type 2 diabetes and DN Male and female, age 25 – 75 years Stable regimen of anti-glycemic medications and RAAS inhibitors ~150 patients total ENDPOINTS: • Change in urine albumin creatinine ratio (UACR) - primary • Safety – primary • Exploratory assessments include changes in cardiometabolic parameters • • • • 31 PlaceboPraliciguatPraliciguat

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED HFpEF: the need Heart failure remains a rising global epidemic with an estimated prevalence of ~38M individuals globally Large and growing prevalence Five-year mortality rates for patients with HFpEF have been reported to range from 55% - 74% HFpEF comprises 44% -72% of new heart failure diagnoses and accounts for approximately half of the heart failure hospitalizations, with frequent readmissions Significant unmet need 32

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED HFpEF: the nitric oxide connection Reduced cGMP Associated with endothelial dysfunction1,2 Chronic microvascular inflammation 3 signaling and titin phosphorylation4 Clinical precedence Chronic microvascular inflammation and endothelial dysfunction are thought to contribute to the development of cardiac and skeletal muscle inflammation and subsequent fibrosis 33 1) Widlansky, et al, JACC, 2003; 2) Franssen et al, 2016, JACC Heart Fail; 3) van Heerebeek et al, 2012, Circulation; 4) Hamdani et al, 2013, Circ Heart Fail; 5) Filippatos et al, 2017, Eur J Heart Fail

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED HFpEF: our solution • • Improve cardiac blood flow Improve oxygen delivery and utilization by skeletal muscle Reduce microvascular inflammation and fibrosis Reduce cardiac stiffness by increasing titin phosphorylation Prevent left ventricular remodeling and disease progression • • • These improvements are expected to increase functional capacity and improve quality of life for patients with HFpEF and also reduce hospitalizations and mortality 34 We believe that praliciguat will improve symptoms of HFpEF by enhancing NO-sGC-cGMP signaling in the heart and periphery to:

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Preclinical data for praliciguat support potential HFpEF utility in In a preclinical model of HFpEF, praliciguat treatment was associated with: • • • Preservation of cardiac function Lower cardiac hypertrophy Lower levels of biomarkers of inflammation 35 Praliciguat was granted Fast Track Designation for the treatment of HFpEF by the FDA

OL NC GUAT PRALICIGUAT 'VER-TAI<GE TED In a and preclinical model of heart failure, lower cardiac hypertrophy rats markers of inflammation in praliciguat-treated Cardiac weight IL-6 _ s 50 -"E -C) -C) 4o C) -.... 4 J: .:= 30 CD I ...J ·C-) I Q) 3 >-- 20 "C E ::::s 0 :e 2 10 G> (/) (/) + 1 0 Control Control Praliciguat Control Control Praliciguat High salt High salt I **p<o.Oli ****p<o.ooo1 vs High-salt Controli LV+S=left ventricular free wall plus ventricular septum **** **

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Phase 2 study ongoing; topline data expected 2H 2019 Ongoing Phase 2 PATIENTS: ENDPOINTS: • CPET: change in peak VO2 – primary • Safety and tolerability – primary • Change in ventilatory efficiency – secondary • Change in 6-minute walk distance – secondary • # CPET responders – secondary • Patient reported outcomes (KCCQ) – secondary • Metabolic: fasting glucose, HOMA-IR, HbA1c, uric acid, lipids • • • Adult patients with HFpEF (EF > 40%) Male and female, age > 45 years ~184 HFpEF patients total 37 12 WEEK TREATMENT PERIOD PlaceboPraliciguat High dose

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED IW-6463: first and only CNS penetrant sGC stimulator for treatment of neurodegenerative diseases Multidimensional pharmacology of sGC stimulation is well-suited to target multiple aspects of neurodegenerative disorders Our translational trial design gives potential for early proof of CNS pharmacology in Phase 1 IW-6463 is being developed as an oral sGC stimulator and has shown preclinical effects on cerebral blood flow, neuroinflammation, neuroprotection, neuronal function We expect to initiate Phase 1 trial in 1Q2019; topline data expected 2H2019 38

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Increased blood flow to brain areas associated with memory and arousal in rats Cerebral Blood Flow treated with Neuroinflammation IW-6463 Neuroprotection Cognitive Function cortical transition areas thalamus ventral hippocampus Reticular activating system sGC stimulator: Peripherally Restricted IW-6463: CNS-penetrant - Increased blood flow to areas associated with memory and arousal in normal rats by fMRI BOLD imaging - 40 Note: data provided in this slide is based on preclinical models

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Anti-inflammatory neuroprotective effects in mice treated with IW-6463 Cerebral Blood Flow Neuroinflammation Neuroprotection Cognitive Function IW-6463 NO sGC GTP cGMP PKG pCREB Neuroinflammation - Increased cGMP and pCREB in rat brain 3D microtissues - - Decreased inflammatory cytokines in rodent microglial cultures and brain 3D microtissues - 41 Note: data provided in this slide based on IW-6463 pretreatment in preclinical models

OLINCIGUAT PRALICIGUAT IW-6463 LIVER-TARGETED LUNG-TARGETED Improved cognitive function in rats treated with IW-6463 Cerebral Blood Flow Neuroinflammation Neuroprotection Cognitive Function Thigmotaxis: tendency to stay close to walls when exploring open spaces, which is associated with cognitive dysfunction and interferes with maze solving - Positive effect on cognitive function in multiple animal models, including both aged and pharmacologically impaired rats - 43 Note: data provided in this slide is based on preclinical models

:v -T A G fE ') L U\IG-A G fED OL NC GdAf PRA CIGUAf Cortical brain activity greater in rats treated with IW-6463 sGC stimulator: Peripherally restricted sGC stimulator: CNS penetrant (IW-6463) 3.0 3.0 ....... ....... Vehicle IWP-830 ....... Vehicle IW-646 2.5 2.5 c. I'CI 2.0 E E c. I'CI 2.0 E E I I'CI I'CI (!) 1.5 !) 1.5 ( 1.0+-----r------.----.---Time (hours) ---.--..... 1.0 +-----r------.----.---Time (hours) ---.--..... 0 2 3 4 0 2 3 4 6 -1 5 6 -1 1 5

IW-6463 OLINCIGUAT PRALICIGUAT LIVER-TARGETED LUNG-TARGETED Expect to initiate first in human studies in Q1 2019 The IW-6463 Phase 1 trial is designed to provide early proof of pharmacology • Safety, tolerability and pharmacokinetic data on single and multiple ascending doses of IW-6463 will be evaluated Evaluate the effects of IW-6463 by using quantitative, objective measures of brain activity including: • • • Quantitative EEG A select battery of well characterized cognitive and motor assessments • This Phase 1 study is designed to translate our observed preclinical effects to humans, potentially demonstrating proof of pharmacology

LIVER-TARGETED Liver-targeted sGC stimulator to maximize the potential to treat serious ver diseases Chronic liver diseases are serious diseases associated with pathologic inflammation and fibrosis and lead to significant morbidity and mortality We have designed sGC stimulators that specifically target the liver This provides the opportunity to maximize hepatic sGC pharmacology with little or no effect on systemic hemodynamics We expect to nominate a development candidate in 1H2019 46

LUNG-TARGETED Lung-targeted sGC stimulator to maximize the potential to treat serious pulmonary diseases There is a clear role for NO-sGC-cGMP signaling in serious pulmonary diseases; sGC stimulation is a clinically validated approach for treatment of Pulmonary Arterial Hypertension (PAH)* We have designed inhaled sGC stimulators that are lung retentive and lung stable with rapid systemic clearance This provides the opportunity to maximize pulmonary sGC pharmacology with little or no effect on systemic hemodynamics We expect to nominate a development candidate in 1H2019 47 *Adempas® (riociguat) approved for the treatment of PAH

Cyclerion Leadership Brian Cali, PhD - Head of IR and Corp Comms • >20 years enterprise leadership—cofounder of Microbia/IRWD Led preclinical R&D, R&D strategy, in licensing, program leadership and portfolio management • Mark Currie, PhD - President Anjeza Gjino - Head of Finance • Extensive research in cGMP signaling pathways and related pharmacology Primary inventor of LINZESS, led discovery/pharmacology for Celebrex and Lunesta • >13 years of finance experience leading and supporting capital allocation and business transformation initiatives at Ironwood and PerkinElmer • Peter Hecht – CEO Mark Gaffney - Head of External Innovation & Corporate Development • • >20 years CEO experience – co-founder of Microbia/IRWD Under his leadership, Ironwood has grown from nine Ph.D. scientists to a commercial biotechnology company • >12 years experience structuring and negotiating licensing arrangements, partnerships and acquisitions Cheryl Gault - Head of Strategy Bill Huyett - CFO • >15 years marketing, sales, new product planning, commercial strategy at Ironwood and Genzyme • • 30-year career at McKinsey and Co Extensive experience in pharma/med device corporate strategy, capital allocation, finance, product development and commercialization, and corporate leadership Chris Wright, MD, PhD - Head of Development oversaw clinical development of Orkambi and Kalydeco Daryn Lewis - Head of People • • • >20 years drug development in rare and orphan diseases; >12 years experience in talent strategy and operations Led organizational growth and transformation initiatives across STEM-centric businesses • Practicing neurologist at Brigham & Women’s Hospital 48

Separation: Cyclerion ready to launch 1H 2019 • • • • Peter Hecht to be Cyclerion CEO effective upon separation Experienced leadership team complemented with new skills Expected to have a non-overlapping board with Ironwood Board (including new Chair) expected to be announced in next 60 days • Cyclerion expected to raise $150-200M equity (~8-12 quarters of funding) to launch; fits broad shareholder feedback that it raise capital with equity & partnerships Expected tax-free distribution of Cyclerion common stock to IRWD shareholders No expected ongoing funding from Ironwood Cyclerion cash use of ~$9M/month until H2 readouts; modular follow-on spending • • • 49 Well-structured Right leadership, right time