A Study to Assess the Effect of Dexpramipexole in Participants With Severe Eosinophilic Asthma.

Inclusion Criteria:

1. Signed informed consent form and assent form, as appropriate

≥18 years of age at Screening Visit 1 Asthma-related criteria

3. Documented physician diagnosis of asthma for ≥12 months prior to Screening Visit 1.

4. Treatment of asthma, participants must satisfy all the below (items a to c):

5. Participants who have received asthma controller medication with medium or highdose inhaled corticosteroids (ICS; ≥500 μg/day fluticasone propionate drypowder formulation daily or clinically comparable, per Global Initiative forAsthma (GINA) 2021) on a regular basis for at least 12 months prior toScreening Visit 1.

6. Documented treatment with a stable dose of either medium or high dose ICS forat least 3 months prior to Screening Visit 1. The ICS may be contained withinan ICS/LABA (long-acting β2 agonist) combination product. Daily oralcorticosteroids are an allowed concomitant medication; participants on dailyoral corticosteroids must be on a stable dose for 3 months before ScreeningVisit 1.

7. Use of one of more additional daily maintenance asthma controller medicationsaccording to standard practice of care is required. Use of a stable dose of anyadditional asthma controller medications must be documented for at least 3months prior to Screening Visit 1.

8. Pre-bronchodilator forced expiratory volume (Pre-BD FEV₁) ≥40% and <80% of predictedat Screening Visit 2.

9. Variable airflow obstruction documented with at least one of the following criteria:

10. Bronchodilator reversibility at Screening Visit 2, as evidenced by ≥12% and ≥200 mL improvement in FEV₁, 15 to 30 minutes following inhalation of 400 μg (four puffs) of albuterol/salbutamol. Participants who do not meet thebronchodilator reversibility inclusion criterion but have ≥10% and ≥160 mLreversibility, may repeat the reversibility spirometry assessment once duringthe Screening period, at an unscheduled visit at least 7 days prior tobaseline.

11. Bronchodilator reversibility, using the criteria above, documented in the past 24 months prior to Screening Visit 1.

12. Peak flow variation of ≥20% over a 2-week period, documented in the past 24months prior to Screening Visit 1.

13. Airflow variability in clinic FEV₁ ≥20% between two consecutive clinic visits,documented in the past 24 months prior to Screening Visit 1.

14. Airway hyperresponsiveness (provocative concentration causing a 20% fall inFEV₁ of methacholine <8 mg/mL) documented in the past past 24 months prior toScreening Visit 1.

15. ACQ-6 ≥1.5 at Screening Visit 2.

16. Documented history of at least two asthma exacerbations requiring treatment withsystemic corticosteroids (intramuscular, intravenous, or oral) within the past 12-month period prior to Screening Visit 1.

General medical history 9. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening Visit 2 and Baseline Visit.

10. WOCBP must use either of the following methods of birth control, from ScreeningVisit 1 through the End of Study Visit:

11. A highly effective form of birth control (confirmed by the investigator). Highlyeffective forms of birth control include: true sexual abstinence, a vasectomizedsexual partner, Implanon, female sterilization by tubal occlusion, any effectiveIntrauterine device (IUD), IUD/intrauterine system (IUS), LevonorgestrelIntrauterine system, or oral contraceptive. Or

12. Two protocol acceptable methods of contraception in tandem. Women not of childbearing potential are defined as women who are either permanentlysterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), orwho are postmenopausal. Women will be considered postmenopausal if they have beenamenorrheic for ≥12 months prior to the planned date of the Baseline Visit withoutan alternative medical cause. The following age specific requirements apply:

13. Women <50 years old would be considered postmenopausal if they have been amenorrheicfor 12 months or more following cessation of exogenous hormonal treatment andfollicle stimulating hormone levels in the postmenopausal range.

14. Women ≥50 years old would be considered postmenopausal if they have been amenorrheicfor 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria: Asthma-related criteria

1. A participant who experiences a severe asthma exacerbation (defined as adeterioration of asthma that results in emergency treatment, hospitalizationdue to asthma, or treatment with systemic corticosteroids) at any time from 4weeks prior to Screening Visit.Participants who experience an asthma exacerbation during the Screening/Run-inPeriod may remain in screening and proceed with study visits 14 days after theyhave completed their course of oral steroids or returned to their pre-ScreeningVisit maintenance dose of oral steroids and the investigator considersparticipant has returned to baseline status.

2. Current diagnosis of diseases which may confound interpretation of this study'sfindings such as allergic bronchopulmonary aspergillosis, eosinophilicgranulomatosis with polyangiitis, eosinophilic gastrointestinal diseases,hypereosinophilic syndrome, chronic obstructive pulmonary disease, idiopathicpulmonary fibrosis.

3. Respiratory infection: Upper or lower respiratory tract, sinus, or middle earinfection within the 4 weeks before Screening Visit 1. Prohibited medications/procedures 5. Treatment with a biologic investigational drugin the last 5 months prior to Screening Visit 1. Treatment with non-biologicinvestigational drugs in the previous 30 days or five-half-lives prior to ScreeningVisit 1, whichever is longer. Treatment with GSK3511294 (long-acting anti-IL-5) inthe past 12 months.

4. Treatment with any of the following monoclonal antibody therapies within 120days prior to Baseline Visit: benralizumab, dupilumab, mepolizumab, reslizumab,omalizumab, tezepelumab, or tralokinumab.

5. Treatment with pramipexole (Mirapex®) within 30 days of Baseline Visit. 8.Treatment with selected drugs known to have a substantial risk of neutropeniain the past 30 days prior to Screening Visit 1.

6. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year. General medical history 10. Weight <40 kg at Screening Visit 2. 11. Current smokingwithin the 12 months prior to Screening Visit 1 or a smoking history of >10pack-years. Smoking includes tobacco, vaping, and/or marijuana use.

7. Known or suspected alcohol or drug abuse 13. Uncontrolled severe hypertension:systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg priorto the Baseline Visit despite antihypertensive therapy.

8. History of malignancy that required surgery (excluding local and wide-localexcision), radiation therapy and/or systemic therapy during the 5 years priorto the Baseline Visit.

9. History of human immunodeficiency virus (HIV) infection or chronic infectionwith hepatitis B or C.

10. A helminth parasitic infection diagnosed within 24 weeks prior to ScreeningVisit 1 that has not been treated with or has failed to respond to standard ofcare (SoC) therapy.

11. Medical or other condition likely to interfere with participant's ability toundergo study procedures, adhere to visit schedule, or comply with studyrequirements.

12. Known or suspected noncompliance with medication. 19. Unwillingness orinability to follow the procedures outlined in the protocol. Clinical safety labs 20. Absolute neutrophil count (ANC) <2.000x10⁹/L at ScreeningVisit 1 or Screening Visit 2.

13. Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² at Screening Visit 2 (using the Bedside Schwartz eGFRformula).

14. Active liver disease defined as any known current infectious, neoplastic, ormetabolic pathology of the liver or unexplained elevations in alanineaminotransferase (ALT), aspartate aminotransferase (AST), >3x the upper limitof normal (ULN), or total bilirubin >2x ULN at Screening Visit 2 confirmed by arepeat abnormal measurement of the relevant value(s), at least 1 week apart. Cardiac safety 23. History of New York Heart Association class IV heart failure orlast known left ventricular ejection fraction <25%.

15. History of major adverse cardiovascular event (MACE) within 3 months prior tothe Baseline Visit.

16. History of cardiac arrhythmia within 3 months prior to the Baseline Visit thatis not controlled by medication or via ablation.

17. History of long QT syndrome. 27. Corrected QT interval by Fridericia (QTcF)interval >450 ms for males and >470 ms for females at Screening Visit 2 or QTcF ≥480 ms for participants with bundle branch block.

18. Clinically important abnormalities in resting ECG that may interfere with theinterpretation of QTcF interval changes at Screening Visit 2, including heartrate <45 beats per minute (bpm) or >100 bpm. Pregnancy/Lactation 29. Pregnant women or women breastfeeding 30. Males who areunwilling to use an acceptable method of birth control during the entire studyperiod (ie, condom with spermicide).