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Interim Phase 2 (Part 1a) Preeclampsia Data July 17, 2025 Transforming Care for Preeclampsia and Stroke
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This presentation contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and forward-looking information that are based on the beliefs of management and reflect management’s current expectations. When used in this presentation, the words “estimate, ” “believe, ” “anticipate, ” “intend, ” “expect, ” “plan, ” “continue, ” “potential, ” “will, ” “may, ” “could, ” “seek, ” “might, ” “project, ” “target, ” “aim” or “should, ” the negative of these words or such variations thereon or comparable terminology and the use of future dates are intended to identify forward-looking statements and information. The forward-looking statements reflect management’s current plans, expectations, intentions, objectives, market opportunity and other estimates, beliefs regarding the benefits and potential of DM199 and anticipated timing of future events, all of which involve assumptions that may never materialize or may prove to be incorrect and inherently involve significant risks and uncertainties, including factors beyond DiaMedica’s control that could cause actual results, performance or achievements, or other future events, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Applicable risks and uncertainties are subject to market and other conditions and include, among others, risks and uncertainties relating to DiaMedica’s clinical expansion into preeclampsia, the ability of its physician collaborators to successfully conduct a Phase 2, proof-of-concept trial of DM199 as a treatment for preeclampsia, DiaMedica’s reliance on its physician collaborators and the ability of other investigators to repeat the interim top-line results; regulatory applications and related filings and approval timelines; the possibility of additional future adverse events associated with or unfavorable results from the preeclampsia or other trials; DiaMedica’s plans to develop, obtain regulatory approval for its DM199 product candidate for the treatment of preeclampsia or other indications and its expectations regarding the benefits of DM199, including its ability to impact blood pressure and improve endothelial health, and the potential market size for DM199 in preeclampsia; DiaMedica’s ability to conduct successful clinical testing of DM199 within its anticipated parameters, including targeted enrollment numbers, costs and timeframes; DiaMedica’s reliance on collaboration with third parties to conduct clinical trials; DiaMedica’s ability to continue to obtain funding for its operations, including funding necessary to complete planned clinical trials and obtain regulatory approvals for DM199 for preeclampsia or other indications and the risks identified under the heading “Risk Factors” in DiaMedica’s annual report on Form 10-K for the fiscal year ended December 31, 2024, and subsequent U.S. Securities and Exchange Commission filings, including its most recent quarterly report on Form 10-Q for the quarterly period ended March 31, 2025. Other risks and uncertainties of which DiaMedica is not currently aware may also affect the Company’s forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. All forward-looking statements contained in this presentation speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. DiaMedica undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. Cautionary Note Regarding Forward-Looking Statements © 2025 DiaMedica Therapeutics. All Rights Reserved. 2
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325,000+ FGR & PE1,2 ~200,000 PE2 ~30,000 Early onset PE3,4 Early-Onset PE and FGR: Severe Conditions with a $5B+ U.S. Market 3 Disease Overview Annual Incidence in U.S. 〉Preeclampsia (PE): life-threatening high blood pressure disorder accompanied by multi-system organ damage that occurs only during pregnancy. – Early onset PE is a severe sub-type that occurs before 34 weeks of pregnancy where 50% of deliveries are driven by refractory hypertension despite maximal intervention6. – There are currently no disease modifying therapies approved for PE. 〉Fetal Growth Restriction (FGR): A condition where a baby is not growing as expected, often due to preeclampsia or other complications. 1. Baschat et al. (2021). FIGO initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction. International Journal of Gynecology & Obstetrics, 152(S1), 3-12. 2. Chappell, L. C., et al. (2021). Pre-eclampsia. The Lancet, 398(10297), 341–354. 3. Teka, H., et al. (2023). Clinical presentation, maternal-fetal, and neonatal outcomes of early-onset versus late onset preeclampsia-eclampsia syndrome in a teaching hospital in a low-resource setting: A retrospective cohort study. PloS one, 18(2), e0281952. 4. E., G., Akurati, et al. (2018). Early onset and late onset preeclampsia-maternal and perinatal outcomes in a rural teritiary health center. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 7(6), 2266–2269. 5. Dall'Asta, A., et al. (2017). Early onset fetal growth restriction. Maternal health, neonatology and perinatology, 3, 2. 6. Paidas, M. J., et al. (2020). Prospective, randomized, double -blind, placebo-controlled evaluation of the pharmacokinetics, safety, an d efficacy of recombinant antithrombin versus placebo in preterm preeclampsia. American Journal of Obstetrics & Gynecology, 223(5), 739.e1-739.e13. ~20,000 Early onset FGR 5* *FGR Only © 2025 DiaMedica Therapeutics. All Rights Reserved. INITIAL TARGETS
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Interim Phase 2 (Part 1a) Results
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5 Interim Phase 2 (Part 1a) Results of DM199 for Preeclampsia are a Clear Success © 2025 DiaMedica Therapeutics. All Rights Reserved. 〉 Safety: No placental transfer of DM199. Well tolerated with no serious TEAEs reported. 〉 Blood Pressure (BP): Dose-dependent reductions in both systolic (SBP) and diastolic (DBP) o Cohort 9 (n=3; highest dose): Achieved the largest mean BP reduction of all cohorts at predefined 5-minute post-infusion timepoint: SBP ↓ 35 mmHg (p<0.05), DBP ↓ 15 mmHg (p<0.05) o Pooled cohorts 6-9 (n=12): Statistically significant mean reductions in SBP and DBP across all predefined post-infusion timepoints—5 minutes, 30 minutes, and 24 hours – SBP: ↓ 25, ↓15, ↓ 20 mmHg at 5 min, 30 min, and 24 hours (p=0.0003, p=0.0018, p=0.0031) – DBP: ↓ 13, ↓ 13, ↓ 10 mmHg at 5 min, 30 min, and 24 hours (p=0.0007, p=0.0002, p=0.0294) 〉 Dilation of intrauterine arteries: Statistically significant improvement in pulsatility index at the 2-hour timepoint1, signaling potential for enhanced placental perfusion and disease modification o ↓ 13.2% reduction in blood flow resistance (p=0.0003) TEAE: Treatment Emergent Adverse Event 1. Uterine Doppler measurements were performed on participants at baseline, 2 hours, and 24 hours; however, as most participants delivered within 24 hours, measurements at the 24-hour timepoint were available for only 5 patients.
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Part 1a- Dose Escalation (3x3 Design) DM199 Preeclampsia Phase 2 IST Trial – Part 1a Women planned for delivery within 72 hours Part 1 Overview 〉 27-42 weeks gestation (singleton) 〉 >150 systolic blood pressure 〉 Receiving standard of care 〉 <72 hours scheduled for delivery Study Groups 〉 1a. Up to 30 preeclampsia participants 〉 Ascending dose study identifying the optimal, medically relevant dose based on BP reductions 〉 1b. 30 preeclampsia participants. Expansion cohort at dose identified in 1A Primary Endpoints: 〉 Safety and tolerability 〉 Includes results of placental crossing analysis/assay 〉 Lower blood pressure Key Exploratory Endpoint 〉 Dilation of uterine arteries (Doppler) 6 〉Study designed to assess DM199 placental transfer with minimal fetal exposure and to evaluate early blood pressure effects. Repeated dosing avoided to prevent prolonged fetal exposure if transfer occured. Limited dosing ( one each IV & SC) minimized fetal exposure risk during this assessment. © 2025 DiaMedica Therapeutics. All Rights Reserved. 0.2µg/kg IV + 1.2µg/kg SC 0.5µg/kg IV + 3.0µg/kg SC 0.75µg/kg IV + 4.5µg/kg SC 1.0µg/kg IV + 6.0µg/kg SC 1.25µg/kg IV + 7.5µg/kg SC 1.5µg/kg IV + 9.0µg/kg SC 0.1µg/kg IV + 0.6µg/kg SC C3 C4 C5 C6 C7 C8 0.1µg/kg IVC1 C2 C9 2.0µg/kg IV + 12.0µg/kg SC
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Time After IV is Completed DM199 Administration Timepoints and Prespecified BP Measurements Timepoints of BP Measurements Approximate Tmax of IV and SC Doses 7© 2025 DiaMedica Therapeutics. All Rights Reserved. Participant Meets Screening Requirement (ie SBP >150 mmHg), is Consented, and Enrolled DM199 IV Infusion SBP/DBP* Baseline Recorded *Average of 3 consecutive measurements IV= Intravenous SC=Subcutaneous …… Prespecified Primary Endpoint + 5 Min SBP/DBP + 30 Min SBP/DBP + 24hr SBP/DBP + ~1hr DM199 SC
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Baseline Demographics 8© 2025 DiaMedica Therapeutics. All Rights Reserved. Characteristics DM199 (n=28) Median (IQR) gestation at enrollment (weeks + days) 37+0 (35+6 - 38+1) Median (IQR) maternal age (years) 32.5 (28.8 - 36.3) Mean (SD), birth weight in grams 2591.3 (553.4) BMI, median (IQR) 36.8 (33.4 - 43.4) Race, n(%) Black 22 (79) Mixed 6 (21) Mean (SD) systolic blood pressure (mmHg) 165.9 (11.7) Mean (SD) diastolic blood pressure (mmHg) 103.3 (9.8) Received antihypertensives 24 hours prior to enrollment, n(%) 1 10 (36) 2 14 (50) 3 4 (14) Received short-acting antihypertensives after randomization, n(%) 8 (29) Received magnesium sulphate, n(%) 27 (96) Received corticosteroids after randomization, n(%) 1 (4) IQR: Interquartile Range SD: Standard Deviation
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Delivery Characteristics 9© 2025 DiaMedica Therapeutics. All Rights Reserved. Characteristics DM199 n(%) Vaginal delivery 9 (32) Cesarean section 19 (68) Time to delivery <2 hours 1 (4) <4 hours 3 (11) <8 hours 9 (32) <12 hours 16 (57) <24 hours 22 (79) ≥24 hours 6 (21) Received balloon catheter 14 (50) Received prostaglandins 9 (32) Received oxytocin 11 (39) 〉~80% of deliveries occurred within 24 hours
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Average Plasma DM199 Concentrations (Maternal and Cord Blood Samples At Delivery) DM199 Was NOT Detected in Umbilical Cord Blood in Any Dose Cohort © 2025 DiaMedica Therapeutics. All Rights Reserved. 10 ND: Non-detectable concentrations – lower limit of quantification is <0.5 ng/mL IV= Intravenous SC=Subcutaneous 1. Did not receive SC dose 2. Data cut for placental transfer was 6/27/25 to allow for sample shipment and analysis. Results for the final C9 patient, enrolled on 7/1/25, are not available 〉At delivery, DM199 was not detected in any cord blood samples, while a clear dose-dependent increase in DM199 was observed in maternal plasma. 〉Data suggests DM199 does not cross the placental barrier, a potentially unique safety advantage. 0.6 1.1 2.3 2.9 2.5 3.3 0 1 2 3 4 Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord C1 & C2 C3 C4 C5 C6 C7 C8 C9 DM199 Concentration (ng/mL)C11 & C2 C3 C4 C5 C6 C7 C8 C92 Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord Mom Cord IV Dose(µg/kg) 0.1 µg/kg 0.2 µg/kg 0.5 µg/kg 0.75 µg/kg 1.0 µg/kg 1.25 µg/kg 1.5 µg/kg 2.0 µg/kg SC Dose(µg/kg) 0.6 µg/kg 1.2 µg/kg 3.0 µg/kg 4.5 µg/kg 6.0 µg/kg 7.5 µg/kg 9.0 µg/kg 12.0 µg/kg ND ND ND ND ND NDND ND ND ND
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Expected Events Of Preeclampsia (per protocol definition) DM199 Was Generally Safe and Well Tolerated © 2025 DiaMedica Therapeutics. All Rights Reserved. 11 〉No serious TEAEs were reported in response to any dose 〉No events of hypotension; 〉No patient paused or discontinued treatment; 〉No induction of early labor Expected Event N=28 [n(%)] Dose Cohorts Postpartum Hemorrhage 4 (14%) C3 (n=2), C4 (n=1), C8 (n=1) Eclampsia 1 (4%) C1 HELLP Syndrome 1 (4%) C4 Pulmonary Edema 1 (4%) C9 Maternal Treatment-Emergent Adverse Events TEAE N=28 [n(%)] Dose Cohorts Nausea 4 (14%) C8 (n=2), C9 (n=2) Headache 3 (11%) C3 (n=1), C6 (n=2) Flushing 1 (4%) C9 TEAE: Treatment Emergent Adverse Event
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DiastolicSystolic Blood Pressure Was Reduced at Prespecified 5-Minute Post-Infusion Endpoint 12 Average Change (mmHg) From Baseline Mean ± SEM presented| Paired T-test vs. baseline| best-fit line based on mean values No patients received short-acting BP meds during these time points Pooled Cohorts C6–C9 achieved statistically significant reductions in SBP (-25 mmHg) and DBP (-15 mmHg) -45 -35 -25 -15 -5 5 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 p<0.05 p<0.05 -25 -20 -15 -10 -5 0 5 10 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.00.10 n=6 169 1&2 IV Dose (ug/kg) Same size Baseline BP Cohort(s) 0.20 n=4 168 3 0.50 n=3 155 4 0.75 n=3 165 5 1.00 n=3 169 6 1.25 n=3 156 7 1.50 n=3 160 8 2.0 n=3 183 9 0.10 n=6 102 1&2 0.20 n=4 98 3 0.50 n=3 109 4 0.75 n=3 105 5 1.00 n=3 105 6 1.25 n=3 97 7 1.50 n=3 103 8 2.0 n=3 112 9 © 2025 DiaMedica Therapeutics. All Rights Reserved. p<0.05 p<0.05 p<0.05 Cohorts 6 – 9 Dose Range For Further Clinical Investigation Cohorts 6 – 9 Dose Range For Further Clinical Investigation
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DiastolicSystolic 13© 2025 DiaMedica Therapeutics. All Rights Reserved. Average Change (mmHg) From Baseline Mean ± SEM presented| Paired T-test vs. baseline | best-fit line based on mean values No patients received short-acting BP meds during these time points 1. Excludes Patient 1 due to delivery occurring 15 minutes after infusion completion (emergency c -section) -35 -25 -15 -5 5 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 -25 -15 -5 5 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 p<0.05 0.10 n=5 163 1&21 0.20 n=4 168 3 0.50 n=3 155 4 0.75 n=3 165 5 1.00 n=3 169 6 1.25 n=3 156 7 1.50 n=3 160 8 2.0 n=3 183 9 0.10 n=5 97 1&21 0.20 n=4 98 3 0.50 n=3 109 4 0.75 n=3 105 5 1.00 n=3 105 6 1.25 n=3 97 7 1.50 n=3 103 8 2.0 n=3 112 9 Cohorts 6 – 9 Dose Range For Further Clinical Investigation Cohorts 6 – 9 Dose Range For Further Clinical Investigation IV Dose (ug/kg) Same size Baseline BP Cohort(s) Blood Pressure Was Reduced at Prespecified 30-Minute Post-Infusion Endpoint Pooled Cohorts C6–C9 achieved statistically significant reductions in SBP (-15 mmHg) and DBP (-13 mmHg)
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1.0-2.0 μg/kg IV (Cohorts 6-9) n=122 DM199 Drove Statistically Significant Systolic Blood Pressure Reduction Pooled Analysis of Cohorts 6 to 9 © 2025 DiaMedica Therapeutics. All Rights Reserved. 14 Mean ± SEM presented| Paired T-test vs. baseline: *p<0.05 | **p<0.01 1. Average of three consecutive readings per timepoint 2. Patients in cohorts 6–8 (n=9) did not receive any short-acting antihypertensive medications after DM199 administration. Patients in cohort 9 (n=3) received short-acting BP medications at various time points after the 30-minute measurement but prior to the 24-hour assessment. Note: measurement timepoints presented as scheduled. Actual measurement times varied Average1 SBP (mmHg) Systolic Blood Pressure Prespecified Primary Endpoint 167 142** 152** 149** 153** 150** 145** 147** 120 125 130 135 140 145 150 155 160 165 170 175 Time After Completion of IV Infusion 2 Hours 4 Hours 12 Hours8 Hours 24 Hours5 Minutes 30 MinutesBaseline Severe hypertension (AJOG) (p=0.0003) (p=0.0018) (p=0.0088) (p=0.0095) (p=0.0008) (p=0.0022) (p=0.0031) -15 -25 -20-22 -17-14 -18
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1.0-2.0 μg/kg IV (Cohorts 6-9) n=122 DM199 Drove Statistically Significant Diastolic Blood Pressure Reduction Pooled Analysis of Cohorts 6 to 9 © 2025 DiaMedica Therapeutics. All Rights Reserved. 15 Average1 DBP (mmHg) Time After Completion of IV Infusion 2 Hours 4 Hours 12 Hours8 Hours 24 Hours5 Minutes 30 MinutesBaseline Diastolic Blood Pressure Prespecified Primary Endpoint Mean ± SEM presented| Paired T-test vs. baseline: *p<0.05 | **p<0.01 1. Average of three consecutive readings per timepoint 2. Patients in cohorts 6–8 (n=9) did not receive any short-acting antihypertensive medications after DM199 administration. Patients in cohort 9 (n=3) received short-acting BP medications at various time points after the 30-minute measurement but prior to the 24-hour assessment. Note: measurement timepoints presented as scheduled. Actual measurement times varied 104 91** 91** 92** 94** 91** 88** 94* 70 75 80 85 90 95 100 105 110 (p=0.0007) (p=0.0002) (p=0.0009) (p=0.0038) (p=0.0029) (p=0.0016) (p=0.0294) -13-13 -10 -17 -13 -11 -13
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DM199 Reduced Uterine Artery Resistance, Suggesting Enhanced Placental Perfusion © 2025 DiaMedica Therapeutics. All Rights Reserved. 16 Overall1,2 (n=25) 1. Measurements not available for one patient in Cohort 1, and two patients in Cohort 7 2. One patient in Cohort 2 (baseline: 2.2, 2hr: 2.5) was crowning (baby's head visible at the vaginal opening) at the time of the 2- hour measurement, potentially impact the 2-hour measurement Geomean % Change1 -13.2% P-value1 0.0003 〉Dilation of the uterine arteries was assessed by Doppler ultrasound at baseline and two hours after IV infusion 〉13.2% average reduction in blood flow resistance was observed across cohorts (p=0.0003), suggesting DM199 increased perfusion to the placenta Cohorts 1&2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7 Cohort 8 Cohort 9 Reduced blood flow resistance 2 0 0.5 1 1.5 2 2.5 Baseline 2 Hours Uterine Artery Pulsatility Index Improved perfusion may reduce placental hypoxia, supporting fetal growth and disease modification
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Summary Remarks © 2025 DiaMedica Therapeutics. All Rights Reserved. 17 DM199 is emerging as an exciting potential therapeutic option for both preeclampsia and fetal growth restriction DM199 appears to be generally well tolerated across broad exposure levels, and does not cross the placental barrier Early signals of improved placental perfusion suggest the potential for true disease modification Robust, durable blood pressure reductions provide broader clinical relevance, indicating endothelial protection—the key driver of maternal disease Ongoing dose optimization is expected to further strengthen DM199’s profile as it advances into U.S. clinical trials next year
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Next Steps for the Phase 2 Trial
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Next Phases of Preeclampsia IST Following Part 1A Completion All parts can enroll concurrently 19© 2025 DiaMedica Therapeutics. All Rights Reserved. Part 1b (n=30) Planned Delivery in 72 Hrs. Part 2 (n=30) Expectant Management Part 3 (n=30) Fetal Growth Restriction ▪ Recruiting the same population as Part 1A: women with planned delivery within 72 hours and SBP >150 mmHg (27 – 42 weeks GA) ▪ Participants will receive a single IV/SC dose on Day 1, using the dose identified in Part 1A (no additional doses) ▪ Primary endpoints: Safety* and lowering blood pressure ▪ Recruiting women with early onset preeclampsia (GA 27+0 to 32+6) who are candidates for expectant mgmt. (prolongation) ▪ Participants will receive an initial IV/SC dose on Day 1, followed by repeated SC doses until delivery ▪ Primary endpoints: Safety* , prolongation, change in UACR, need to increase/decrease antihypertensive agents ▪ Recruiting women with early onset FGR (GA 27+0 to 32+6), defined as fetal growth <3rd centile, who do not have preeclampsia ▪ Participants will receive an initial IV/SC dose on Day 1, followed by repeated SC doses until delivery ▪ Primary endpoints: Safety* , changes in uterine, ophthalmic, and fetal Dopplers, and birthweight centile GA= Gestational Age *including placental transfer of DM199 (umbilical cord levels after birth)
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Fetal Growth Restriction: DM199’s Indication Expansion 〉Fetal Growth Restriction is a Major Unmet Medical Challenge – Placental insufficiency—particularly impaired uteroplacental blood flow—is a core pathophysiologic driver of FGR – No approved therapies to directly treat FGR; current management is limited to monitoring and early delivery – The Pulsatility Index (PI) in uterine and umbilical arteries is a core diagnostic and prognostic biomarker and is directly correlated with fetal oxygen/nutrient delivery © 2025 DiaMedica Therapeutics. All Rights Reserved. 20 〉DM199 Offers the Potential to Improve Uteroplacental Blood Flow – Like preeclampsia, FGR is often marked by abnormal uterine artery Doppler waveforms: • Elevated PI • Absent or reversed end-diastolic flow – DM199 has been shown to dilate intrauterine arteries, resulting in: • Improved uteroplacental perfusion • Reduced vascular resistance, as quantified by the Pulsatility Index DM199’s efficacy in lowering PI in preeclampsia patients supports its potential in FGR—especially early-onset forms Strong mechanistic rationale based on Interim Part 1a PE data
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