Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic and Preliminary Clinical Activity of Briquilimab in Adult Patients with Chronic Spontaneous Urticaria (CSU)

Inclusion Criteria:

1. Written informed consent after the nature of the trial has been fully explained andbefore performing any trial related assessments

2. Males and females, ≥18 years old

3. i. For Cohorts 1, 2, 3, 4a, 4b, 5, 5b, 6 and 7: Diagnosis of symptomatic CSU despitetreatment as defined by:

4. Diagnosis of CSU for ≥ 6 months

5. The presence of itch and hives for ≥ 8 consecutive weeks at any time prior toScreening despite current use of H1-antihistamines (as reported by theparticipant)

6. The presence of itch and hives for ≥ 8 consecutive weeks at any time prior toScreening despite treatment with omalizumab or intolerance to omalizumab (asreported by the participant)

7. UAS7 of ≥ 16 and ISS7 of ≥ 8 on 7 consecutive days between Day -10 throughDay-1 of Screening ii. For Cohorts 8 and 9: Diagnosis of symptomatic CSU despite treatment as definedby:

8. Diagnosis of CSU for ≥ 6 months (as per local and international guidance)

9. The presence of itch and hives for ≥ 8 consecutive weeks at any time prior toScreening despite current use of H1-antihistamines (as reported by theparticipant)

10. Participants may be omalizumab naïve or have been previously exposed toomalizumab independent of treatment duration or response

11. UAS7 of ≥ 16 and ISS7 of ≥ 8 on 7 consecutive days between Day -10 through Day -1 of Screening

12. Use of H1-antihistamines on stable dose up to four-fold of the approved dose sinceScreening and not expected to change during first 12 weeks of the trial

13. Blood counts at Screening with:

14. Hemoglobin: ≥ 11 g/dl

15. Platelets: ≥ 100,000/mm3

16. Leucocytes: ≥ 3,000/mm3

17. Neutrophils: ≥ 2,000/mm3

18. Willing and able to complete a daily diary for the duration of the trial and adhereto the trial visit schedule

Exclusion Criteria:

1. Women who are pregnant or nursing or intend to become pregnant during the course ofthe trial

2. Dominant comorbid chronic urticaria with a clearly defined predominant or soletrigger (chronic inducible urticaria) including urticaria factitia (symptomaticdermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-,cholinergic-, or contact urticaria

3. Other active diseases with possible symptoms of urticaria, wheals or angioedema,including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1inhibitor deficiency)

4. Any other active skin disease associated with chronic itching that might confoundthe trial evaluations and results, in the opinion of the Investigator (e.g., atopicdermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.)

5. History of anaphylaxis

6. Any H2 antihistamine, leukotriene receptor antagonist or tricyclic antidepressantuse within 3 days prior to Screening

7. Experimental monoclonal antibody therapy (e.g., dupilumab, ligelizumab, etc.) within 6 months or Janus kinase (JAK) inhibitors within 5 half-lives prior to first IPdosing

8. Immunosuppressive therapy (e.g., systemic corticosteroids, cyclosporine,methotrexate, dapsone, cyclophosphamide, tacrolimus and mycophenolate mofetil,hydroxychloroquine, etc.) within 4 weeks (or 5 half-lives, whichever is longer)prior to first IP dosing

9. Electrocardiogram (ECG) findings at Screening that are considered clinicallysignificant

10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x Upperlimit of normal (ULN) at Screening

11. Serum total bilirubin >1.5 x ULN, unless attributable to Gilbert's syndrome

12. Estimated creatinine clearance (eCrCl) by Cockcroft-Gault equation using total bodyweight < 60 mL/min

13. Known HIV+, active hepatitis B or hepatitis C infection, or acute/long-COVID

14. Major abdominal or thoracic surgery within 8 weeks prior to Screening or plannedsurgery during trial participation

15. Male participants (who are not vasectomized) who are not willing to use highlyeffective contraceptive methods (when having sexual intercourse with a femalepartner of childbearing potential, Section 8.2) and who are not willing to abstainfrom sperm donation during the trial and for at least 150 days after last IP dosing.A male participant is considered vasectomized if he had a vasectomy at least 4months prior to Screening and if he has received post-surgical medical assessment ofthe surgical success of the vasectomy.

16. Female participants of childbearing potential not willing to use highly effectivecontraceptive methods (Section 8.2) during the trial and for at least 150 days afterlast IP dosing. Women of nonchildbearing potential, must be surgically sterile (i.e., had undergone complete hysterectomy, bilateral oophorectomy, or tuballigation) or be in menopausal state (at least 1 year without menses).

17. Participation in another research trial involving the use of an IP within the last 30 days (or 5 halflives of IP, whichever is longer) prior to Screening

18. Any known contraindications or hypersensitivity to any component of the IP, drugs ofsimilar chemical classes (i.e., to murine, chimeric or human antibodies) orantihistamines or leukotrienes

19. Any other acute or chronic medical or psychiatric condition or laboratoryabnormality that could increase the risk associated with trial participation or IPadministration or could interfere with the interpretation of trial results and, inthe judgment of the Investigator, would make the participant inappropriate for entryinto the trial

20. Participants not willing to abstain from blood donations while being on the trial (until EOT Visit)

21. Close affiliation with the Investigator (e.g., a close relative, financiallydependent on the trial site) or participant who is an employee of the Sponsor'scompany