Effect of Linvemastat in Patients With Partially Controlled Asthma (syMMPonia)

Inclusion Criteria:

• Patients aged 18 - 85 years at the time of signing informed consent

• Patient is able to provide written informed consent.

• Documented physician´s diagnosis of Type 2 high asthma, as per the Global Initiativefor Asthma (GINA) 2023 guideline 2023 at Screening.

• Patients with existing treatment with at least low to medium doses of ICS therapy incombination with LABA as a second controller for at least 90 days and astable/optimized dose ≥30 days prior to Day 1. Patients on triple therapy with along-acting muscarinic antagonist (LAMA) will be excluded.

• An ACQ score ≥ 1.5 at Screening.

• Patients with a pre-bronchodilator FEV1 value of 40% to 80% of the patient'spredicted value at Screening.

• Patients must have experienced at least once, within 2 years prior to Screening, oneof the following asthma exacerbation events: Treatment with a systemic steroid (oralor parenteral) for worsening asthma. Hospitalization or emergency medical care visitfor worsening asthma.

• Males with a partner of childbearing potential must use a condom for the duration ofstudy treatment and at least 96 hours after discontinuing the study drug.

• Female patients of childbearing potential (including those < 1 year post-menopausal)must use a highly effective method of contraception per Clinical Trial FacilitationGroup (CTFG) recommendation during the conduct of the study and for 30 days afterthe last dose of study drug. Highly effective contraceptive measures for femalepatients of childbearing potential include: combined (estrogen and progestogencontaining) hormonal contraception associated with inhibition of ovulation: oral,intravaginal, transdermal. Progestogen-only hormonal contraception associated withinhibition of ovulation: oral, injectable, implantable. intrauterine device (IUD),intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomizedpartner (when partner is the sole sexual partner of the female patient and when thepartner has received medical assessment of the surgical success), sexual abstinence.

• Women not of childbearing potential are defined as: Post-menopausal women (definedas at least 12 months with no menses without an alternative medical cause); in women <45 years of age, a high follicle-stimulating hormone (FSH) level in thepost-menopausal range may be used to confirm a post-menopausal state in women notusing hormonal contraception or hormonal replacement therapy; OR Have had ahysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateraltubal ligation/occlusion at least 6 weeks prior to Screening OR Have a congenital oracquired condition that prevents childbearing.

Exclusion Criteria:

• Pregnant or breastfeeding.

• Current smoker (including vaping) or cessation of smoking within the 6 months priorto Day 1, or > 10 pack-year history of smoking.

• Participation in another clinical trial of an investigational agent within 3 months (small molecule) / 6 months (biologics) or 5 half-lives (if known) of the agent,whichever is longer, prior to randomization.

• Evidence of COVID-19 infection at Screening, as judged by the Investigator.

• Advanced congestive heart failure [New York Heart Association (NYHA) class 3 or 4].

• Known hypersensitivity to any component of the formulation of linvemastat or anycomponent of the excipient.

• Live or messenger ribonucleic acid (mRNA) vaccination within 2 weeks before Day 1 orinoculation with a live or mRNA vaccine is planned during study participation.

• History of solid organ transplant.

• Anti-immunoglobulin E (IgE) therapy [e.g., omalizumab (Xolair®)] within 130 daysprior to Screening or any other biologic therapy [including anti-TSLP, anti-IL-4/4Ror IL-5/5R monoclonal antibodies (mAb)] or systemic immunosuppressant (e.g.,methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoidarthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupuserythematosus, multiple sclerosis) and other diseases, within 2 months or 5half-lives prior to Screening, whichever is longer.

• Evidence of active tuberculosis (TB) infection at Screening, as judged by theInvestigator.

• Active acute or chronic psychiatric illness that, in the opinion of theInvestigator, may prevent from complying with study instructions.

• Known positive history of malignancy within 5 years of Screening (with the exceptionof basal cell skin cancer, carcinoma in-situ of the cervix, or low-risk prostatecancer after curative therapy).

• Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) infection at Screening.

• Concurrent emphysema.

• Use of any therapeutics that are strong inhibitors and inducers of CYP3A4 or CYP2C8 [e.g., rifampicin, ketoconazole, phenytoin, ritonavir, macrolide antibiotics (e.g.,telithromycin), and carbamazepine].

• History of liver dysfunction, including patients with moderate (Child-Pugh B) orsevere (Child-Pugh C) impairment or disordered coagulation.

• Abnormal ECG: ventricular arrhythmias (non-sustained ventricular tachycardia [VT],multifocal or frequent premature ventricular contractions, clinically significantbundle branch block or axis deviation [as assessed by PI], or abnormal Q waves). Inthe case of a corrected QT interval using Fridericia's formula (QTcF) interval >450ms (men) or >480 ms (women; patients with bundle branch block) or PR (P to QRS)interval outside the range of 120 to 220 ms, the assessment may be repeated once foreligibility determination at Screening or Baseline.

• Known uncontrolled hypertension or diabetes at the discretion of the Investigator.

• Any condition that required hospitalization (except for asthma exacerbation) withinthe 3 months prior to Day 1 or is likely to require so during the study.

• Clinically significant abnormalities in the Screening physical examination, medicalhistory, vital signs, ECG, or clinical laboratory tests that are not known to be dueto concurrent asthma in the opinion of the Investigator and Medical Monitor shouldpreclude the patient's participation in the clinical study.

• The following laboratory parameters are excluded:

1. Hemoglobin (Hg) <10 g/dL (100 g/L)

2. White blood cells (WBC) < 3000/μL (< 3000/mm3). African American patients whoare known to have low WBC of < 3000/μL but ≥ 1500/μL will be eligible.

3. Platelet count < 70,000/μL (70,000/mm3)

4. Serum creatinine > 1.5 x upper limit of normal (ULN)

5. Glomerular filtration rate ≤ 60 mL/min/1.73 m2 or evidence of acute kidneyinjury or history of severe hypersensitivity reactions to gadolinium-basedcontrast agents

6. Serum total bilirubin > 1.5 ULN

7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 xULN or serum alkaline phosphatase > 2 x ULN