A Study to Investigate Safety, Tolerability and Pharmacokinetics of LAE103 or LAE103 in Combination With LAE102 in Healthy Overweight/Obese Participants

Inclusion Criteria:

1. Informed consent: Are capable of giving signed informed consent and comply with the requirements and restrictions listed in the ICF and in this protocol.

2. Age at the time of signing the ICF:

   1. Parts A, C, and D: Male or female participants aged 18 to 55 years, inclusive. Each cohort must include at least 3 female and 3 male participants.
   2. Part B: Female participants aged 45 to 75 years, inclusive.

3. BMI at screening:

   1. Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive).
   2. Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive).

4. For female participants:

   1. Participants without childbearing potential: defined as either postmenopausal or surgically sterile: including surgical sterilization (recorded bilateral salpingectomy, hysterectomy, or bilateral oophorectomy at least 6 weeks before screening visit); postmenopausal women defined as an individual who has had at least 12 months of spontaneous amenorrhea without an alternative medical cause and a FSH level in the postmenopausal range (≥ 40 IU/L at screening), or
   2. Participants with childbearing potential, non-pregnant, non-lactating, must agree to use two forms of effective methods of contraception (at least one form must be highly effective) for the duration of the study, and 130 days after the last investigational product administration. During this period, participants should not donate eggs. Serum hCG test must < 5 mIU/mL at both the screening visit and D-1. Hormonal contraceptives should be commenced one month prior to screening to ensure contraceptive is in full effect.

   Complete abstinence is acceptable if it is part of the participant's usual and preferred lifestyle. Participants who are in same-sex relationships and continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per protocol (This would only apply to Parts A, C, and D, details of contraception guidance refer to 12.3).

5. Male participants with female partners of childbearing potential must agree to use adequate methods of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner for the duration of the study and for 130 days after the last dosing. Male participants are not allowed to donate sperm for the same period. Hormonal contraceptives used by the female partner should have commenced one month prior to screening to ensure contraceptive is in full effect.

6. Type of participant and disease characteristics

   1. Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
   2. Have FSH levels ≥ 40 IU/L at screening (Part B only).

   3. Have liver function tests and all other clinical laboratory tests results within the normal range for the population, or results deemed not clinically significant at the discretion of the investigator.

      Note: except for minor deviation judged to be acceptable by the investigator. Retesting may occur once during the screening visit at the discretion of the investigator.

   4. Have venous access sufficient to allow for blood sampling as per the protocol or have no anticipated contraindications to receiving investigational products via SC delivery.
7. Are willing to make themselves available for study visits for the duration of the study and are willing to follow study procedures.

Note: For Part D optional cohort, inclusion criteria for the additional 2 postmenopausal women can be referred to Part B if their enrollment is planned

Exclusion Criteria:

1. Informed consent: Are capable of giving signed informed consent and comply with the requirements and restrictions listed in the ICF and in this protocol.

2. Age at the time of signing the ICF:

   1. Parts A, C, and D: Male or female participants aged 18 to 55 years, inclusive. Each cohort must include at least 3 female and 3 male participants.
   2. Part B: Female participants aged 45 to 75 years, inclusive.

3. BMI at screening:

   1. Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive).
   2. Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive).

4. For female participants:

   1. Participants without childbearing potential: defined as either postmenopausal or surgically sterile: including surgical sterilization (recorded bilateral salpingectomy, hysterectomy, or bilateral oophorectomy at least 6 weeks before screening visit); postmenopausal women defined as an individual who has had at least 12 months of spontaneous amenorrhea without an alternative medical cause and a FSH level in the postmenopausal range (≥ 40 IU/L at screening), or
   2. Participants with childbearing potential, non-pregnant, non-lactating, must agree to use two forms of effective methods of contraception (at least one form must be highly effective) for the duration of the study, and 130 days after the last investigational product administration. During this period, participants should not donate eggs. Serum hCG test must < 5 mIU/mL at both the screening visit and D-1. Hormonal contraceptives should be commenced one month prior to screening to ensure contraceptive is in full effect.

Complete abstinence is acceptable if it is part of the participant's usual and preferred lifestyle. Participants who are in same-sex relationships and continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per protocol (This would only apply to Parts A, C, and D, details of contraception guidance refer to 12.3). LAEKNA LAE103INT1001 Protocol Version 5.0/2026.08.31 CONFIDENTIAL Page 74 of 1455) Male participants with female partners of childbearing potential must agree to use adequate methods of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner for the duration of the study and for 130 days after the last dosing. Male participants are not allowed to donate sperm for the same period. Hormonal contraceptives used by the female partner should have commenced one month prior to screening to ensure contraceptive is in full effect.

6) Type of participant and disease characteristics

a) Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. b) Have FSH levels ≥ 40 IU/L at screening (Part B only). c) Have liver function tests and all other clinical laboratory tests results within the normal range for the population, or results deemed not clinically significant at the discretion of the investigator. Note: except for minor deviation judged to be acceptable by the investigator. Retesting may occur once during the screening visit at the discretion of the investigator. d) Have venous access sufficient to allow for blood sampling as per the protocol or have no anticipated contraindications to receiving investigational products via SC delivery.

7) Are willing to make themselves available for study visits for the duration of the study and are willing to follow study procedures. Note: For Part D optional cohort, inclusion criteria for the additional 2 postmenopausal women can be referred to Part B if their enrollment is planned

Exclusion Criteria:

Medical Conditions:

1. Have a history or presence of clinically significant medical condition(s) including, but not limited to, any

   1. cardiovascular, cerebrovascular, gastrointestinal (including hepatic) diseases.

   2. diabetes, or glycated hemoglobin (HbA1c) ≥ 6.5% or fasting blood glucose ≥ 7.0 mmol/L, medullary thyroid carcinoma, type 2 multiple endocrine neoplasia, chronic pancreatitis, and thyroid disorders.

      Note: Participants who have been on steady dose of thyroid replacement therapy for at least 90 days prior to screening, can be included in the study.

   3. conditions affecting skin, respiratory, cardiovascular, digestive, renal, blood, endocrine,reproductive system.
   4. diagnosed with secondary overweight or obesity, such as obesity caused by metabolic diseases (such as Cushing's syndrome, hypothyroidism, etc.) or drug-induced obesity(such as glucocorticoids, tricyclic antidepressants, atypical antipsychotic drugs, etc.).
   5. psychiatric or neurological disease.
   6. neuromuscular disorder including, but not limited to multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, muscular dystrophy, or amyotrophic lateral sclerosis.
   7. inflammatory or autoimmune diseases that may cause muscle wasting, including, but not limited to systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).
   8. inflammatory myopathies, including but not limited to polymyositis or dermatomyositis.
   9. other disease, abnormality or physiological conditions that would pose an unacceptable risk to study participants or confound the interpretation of the data collected during the study.
   10. individuals who have had a diagnosis of acute pancreatitis.
   11. individuals who have self-perceived dullness or loss of sensation on either side of their abdomen; or have, in the investigator's opinion, excessive tattoos or scars over the arm, thigh, abdomen or other factors (for example rash, excessive fold of skin) that, would interfere with injection-site assessments.

2. Have a history of any malignancy within the past 5 years other than

   1. basal cell or squamous epithelial carcinomas in situ,
   2. cervical carcinoma in situ that have been resected with no evidence of metastatic diseases for 3 years.
3. Have a fasting serum triglyceride level of more than 500 mg/dL(5.6 mmol/L) at screening.

4. Have an estimated glomerular filtration rate (eGFR) calculated by chronic kidney diseaseepidemiology (CKD-EPI) creatinine 2021 equation

   1. less than 90 mL/min/1.73 m2 at screening for Part A, C, and Part D
   2. less than 60 mL/min/1.73 m2 at screening for Part B. Note: Creatine level within normal range, or out of the normal range but deemed nonclinically significant by the investigator can be enrolled.

5. Have

   1. an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study, or
   2. confirmed supine Fridericia's corrected QT (QTcF) interval greater than 450 msec for males and greater than 470 msec for females at screening.

   Note: A mean value will be used to assess the exclusion criterion when triplicate measurements will be made as per protocol.

6. Have an abnormal blood pressure defined as:

   1. diastolic blood pressure greater than 90 mmHg, or less than 50 mmHg
   2. systolic blood pressure greater than 140 mmHg, or less than 90 mmHg Note: except for minor deviation judged to be acceptable by the investigator, or mild to moderate hypertension that is well-controlled with no more than one antihypertensive medication and no changes to hypertension medication within the last three months. Retesting may occur once during the screening visit at the discretion of the investigator.

7. Show evidence at screening of:

   1. human immunodeficiency virus (HIV) or positive human HIV antibodies
   2. hepatitis C or positive hepatitis C antibodies
   3. hepatitis B or positive hepatitis B surface antigen.

8. Have

   1. a history of, or known hypersensitivity to study intervention or its excipients, or
   2. a history of, or know hypersensitivity to monoclonal antibody drugs, or
   3. a history of any severe allergies (including any food or drug allergies).
9. Underwent major surgery within 30 days prior to study intervention administration or plan to undergo major surgery during the study.
10. Self-reported weight change is more than 5% in the previous 3 months prior to screening.

11. Engaged in regular weightlifting, fitness, or strength training aimed at enhancing muscle strength.

    Prior/Concomitant Therapy

12. Use of GLP-1 receptor agonists, or weight loss medications such as orlistat, naltrexone/bupropion, or systemic corticosteroids (oral or intravenous for more than 7 days), or psychiatric medications (e.g., tricyclic antidepressants, olanzapine) within 3 months prior to the first dose of the investigational product.

13. Have used in the past 90 days (before screening) or intend to use during the study any medication that may affect FSH levels, including but not limited to:

    1. hormonal replacement therapy (except for topical vaginal administration)
    2. systemic corticosteroids therapy longer than 2 weeks, or
    3. growth hormone therapies.

14. Have used or intend to use prescription or over the counter medications, or herbal medicines, from 7 days or 5 half-lives (if known), whichever is longer, prior to study intervention administration until the last visit.

    Note: Occasional paracetamol/acetaminophen (up to 2 g/day), vitamins (at recommended daily doses, and approved by the investigator), ibuprofen (up to 0.4 g/day), topically applied eye, or nasal drops and ointments with no clinically significant systemic exposure are allowed.

15. Received any vaccine 30 days prior to screening or plan to receive any vaccine during the study.

    Prior/Concurrent Clinical Study Experience

16. Have participated, are currently enrolled in, or discontinued from a clinical trial involving an investigational drug or device or off-label use of a drug or device within the last 30 days, or 5-half-lives (if known, whichever is longer), of the last administration of study drug or application of the device, or any other type of medical research judged not to be scientifically or medically compatible with this study.

17. Have previously completed or withdrawn from this study or any other study investigating this study intervention.

    Lifestyle Considerations

18. Have

    1. an average weekly alcohol consumption exceeding 14 units per week for female participants, 21 units per week for male participants, or
    2. positive alcohol test at screening or admission, or
    3. a history of alcohol abuse disorder within 1 year prior to screening, or
    4. an inability or unwillingness to stop alcohol consumption 7 days prior to dosing.

    Note: 1 unit of alcohol is defined as 12 oz (360 mL) of beer, 5 oz (150 mL) of wine, or 1.5 oz (45 mL) of distilled spirits. Repeated alcohol breath testing within 24 hours are permitted at investigator's discretion.

19. Have

    1. known or suspected history of substance abuse (such as morphine, methamphetamine, ketamine, methylenedioxyamphetamine, tetrahydrocannabinol) deemed clinically significant by the investigator, or
    2. test positive for drugs of abuse at screening or admission. Note: Repeated DOA testing within 24 hours are permitted at investigator's discretion.

20. Are

    1. smoking more than 5 cigarettes (or the equivalent of other tobacco products) per day within 90 days prior to screening, or
    2. unable or unwilling to stop smoking tobacco products during the confinement peirod.

    Note: A positive result for cotinine is non-exclusionary.

21. Have donated blood or experienced blood loss of more than 400 mL within 30 days prior to screening.

22. Are

    1. fasting or receiving weight loss treatment within 30 days prior to study intervention administration, or
    2. experiencing major changes in lifestyle (e.g., abrupt initiation of a dietary regimens or an augmenting physical activities aiming to lose weight).

    Other Exclusion Criteria

23. In the opinion of the investigator or Sponsor and medical monitor, are unsuitable for inclusion in the study.
24. Are Laekna Limited. employees, CRO employees, investigator, or site personnel directly affiliated with this study or the immediate families of any of these. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
25. Have contraindications for MRI scan or do not meet the requirements for MRI scan as per local guideline. (This criterion applies only to Parts C and D.)