Study to Evaluate the Effect on Obesity of QW Nimacimab and QW Nimacimab Co-administered With Semaglutide vs Placebo

Inclusion Criteria:

1. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

2. Participants must be at least 18 years of age or the legal age of consent in thejurisdiction in which the study is taking place to 65 years, inclusive, at the timeof signing the informed consent.

3. Male, female, and/or nonbinary participants.

4. Have Body Mass Index (BMI) of

5. ≥ 30 kg/m2 to ≤ 45 kg/m2 OR

6. ≥ 27 kg/m2 and < 30 kg/m2 with clinically confirmed diagnosis of at least 1 ofthe following weight-related co-morbidities: i. dyslipidemia: on lipid-lowering medication or having low-density lipoprotein (LDL) ≥ 160 mg/dL (4.1 mmol/L) or triglycerides ≥ 150 mg/dL (1.7 mmol/L) orhigh-density lipoprotein (HDL) < 40 mg/dL (1.0 mmol/L) for men or HDL < 50 mg/dL (1.3 mmol/L) for women at screening. ii. cardiovascular disease: (for example, ischemic cardiovascular disease, New YorkHeart Association [NYHA] Functional Classification Class I-II heart failure). iii. obstructive sleep apnea syndrome (Salzano 2021). iv. controlled arterial hypertension with systolic blood pressure (SBP) < 150 mmHgor diastolic blood pressure (DBP) < 90 mmHg.

7. Have an HbA1c <6.5% at screening.

8. Have had a stable body weight for the 3 months prior to screening (no more than 5%body weight gain and/or loss).

9. If on cardiovascular, anti-hypertensive, must be controlled controlled on a stabledose for 3 months prior to randomization.

10. If on hormone replacement therapy, must be on a stable dose for at least 3 monthsprior to screening, including use of thyroxine.

11. Females of childbearing potential must agree:

12. to use an approved method of contraception from screening throughout the studyand for at least 90 days after the last dose of study drug.

13. to not donate ova from screening throughout the study and for at least 90 daysafter the last dose of study drug.

14. have a negative pregnancy test at screening and Day 0.

15. Male participants who are (hetero) sexually active must agree that he and hispartner will each use an approved method of contraception from screening throughoutthe study and for at least 90 days after the last dose of study drug.

16. Agreement in male participants to not donate sperm from screening throughout thestudy and for at least 90 days after the last dose of study drug.

Exclusion Criteria:

1. Have any prior diagnosis of type 1 or type 2 diabetes mellitus (T1DM or T2DM, orrare forms of diabetes mellitus).

2. Have at least 1 laboratory value suggestive of diabetes during screening, including 1 or more of HbA1c ≥ 6.5% (48 mmol/mol), fasting serum glucose ≥ 126 mg/dL (7.0mmol/L), or random glucose ≥ 200 mg/dL (11.1 mmol/L).

3. Have a prior or planned surgical treatment for obesity (excluding liposuction orabdominoplasty, if performed > 1 year prior to screening).

4. Have obesity induced by other disorders (for example, Cushing's syndrome) ordiagnosed monogenetic or syndromic forms of obesity (for example, Melanocortin 4Receptor deficiency or Prader-Willi Syndrome) or use of systemic corticosteroids oruncontrolled hypothyroidism. (Hypothyroidism on stable treatment is allowed ifthyroid stimulating hormone (TSH) measure within the last 3 months of screening iswithin normal limits).

5. Have had at any time or plan to have endoscopic and/or device-based therapy forobesity including but not limited to the following:

6. Mucosal ablation,

7. Gastric artery embolization,

8. Intragastric balloon, OR

9. Duodenal-jejunal endoluminal liner

10. Surgery of any kind within 3 months prior to Day 0 (Baseline) with the exception ofminor procedures or determined by the Investigator to be clinically relevant forparticipation in the study, or any planned surgery during the study.

11. Renal impairment as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2,calculated at screening using the recommended method for estimating eGFR in adultsfrom the National Kidney Foundation Chronic Kidney Disease EpidemiologyCollaboration (CKD-EPI 2021) equation (Charles 2024).

12. Acute kidney injury or dialysis within the last 3 months prior to the screeningvisit

13. Current malignancy with the exception of participants with basal cell carcinoma ofthis skin, suqamous cell carcinoma of the skin, or carcinoma in situ (e.g., breastcarcinoma, cervical cancer in situ) that have undergone potentially curativetherapy.

14. Positive results at screening that indicate an active virological infection atscreening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus.

15. Previous organ or bone marrow transplant.

16. History and/or confirmed seizure disorder; reports febrile and/or idiopathicseizures occurring within the past 2 years.

17. Unstable cardiovascular disease as determined by the Investigator or medical historyof myocardial infarction or arterial thromboembolic events within 3 months prior toscreening or severe or unstable angina, NYHA Class III or IV disease, or a 12-leadECG showing QTc interval (Fridericia's formula) >450 msec (males) or >470 msec (females), any tachyarrhythmia, pathologic Q waves, or any other abnormality deemedclinically significant in the opinion of the investigator.

18. History or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the study, interfere with the participants'participation for the full duration of the study, or is not in the best interest ofthe participants to participate in the opinion of the Investigator.

19. Have history of any of the following:

20. Major Depressive Disorder (MDD)

21. A lifetime history of suicide attempts

22. Other severe psychiatric disorder(s) (e.g., schizophrenia, bipolar disorder,etc.)

23. Use of anti-depressant medication

24. Have a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10 at screening and/or Day 0 (Baseline).

25. At screening or Day 0 (Baseline) have any suicidal ideation of type 4 or 5 on theColumbia Suicide Severity Rating Scale (C-SSRS) or any suicidal behavior in thelifetime or previous month.

26. History or presence of drug abuse (including medicinal and recreational marijuanause) within the 1 year prior to Day 0 (Baseline) or urine drug assay at screening orDay 0 (Baseline) positive (includes: amphetamines, barbiturates, cocainemetabolites, opiates, benzodiazepines, and cannabinoids).

27. Prior exposure to study drugs

28. Nimacimab injection

29. Glucagon-like peptide-1 (GLP-1) agonist.

30. Allergy to active or inactive component of Nimacimab

31. Allergy to active or inactive component(s) of GLP-1 agonist

32. Female participants who are pregnant or breastfeeding or expecting to conceivechildren within the projected duration of the study.

33. Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 3 × upper limit ofnormal (ULN) at screening. One repeat test may be allowed within 7 days of thereceiving the result, at the discretion of the Investigator.

34. Absolute neutrophil count ≤ 1.5 × 109/L.

35. Platelets ≤ 120 × 109/L.

36. Hemoglobin (Hgb) < 13.5 g/dL in males and < 12 g/dL in females.

37. Currently or have participated in a study of an investigational product or used aninvestigational device within 12 weeks and/or 5 times the half-life of theinvestigational product prior to the (Day 0, Baseline) first dose of studytreatment.

38. Current use of any medication that is known to cause weight loss or participation ina structured weight loss program within the last 6 months prior to screening

39. Employees of the Sponsor, contract research organization (CO) involved in theconduct of the study, or investigational site, or immediate family members of theemployees.

40. History of regular alcohol consumption exceeding 14 drinks/week for females or 21drinks/week for males (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] ofbeer of 1.5 ounces [45 mL] of hard liquor) within 6 months of screening.

Study Extension Eligibility Criteria

Participants are eligible to be included in the extension only if all the following criteria apply:

1. Completed Week 26 of the Main study including Week 25 on study treatment.Participants who completed Week 26 of the Main study but discontinued studytreatment prior to that visit are not eligible to participate.

2. Participants in the combination arms (Nimacimab Injection or placebo +Semaglutide) of the Main study must roll over within 4 weeks of Main study Week 26

3. Participants in the monotherapy arms (Nimacimab Injection or placebo) of theMain study can roll over anytime after they have completed Week 26 on studytreatment but before completing the 13-week follow-up period.

4. Does not have any condition that interferes with the ability to complete theExtension in the judgment of the investigator.