Evaluation of Safety, Efficacy and Thermogenesis-induction of RZL-012 in Overweight and Obese Volunteers

Obesity is a direct result of food-intake in excess of body energy expenditure. Therefore, a
feasible approach to combat obesity is via energy-consuming activities, such as physical
exercise. Unfortunately, our modern society is moving in the other direction, spending more
time in immobilized positions, at work and at home. An alternative strategy for the induction
of increased energy expenditure is via the activation of thermogenic cells that utilize fat
to produce heat.RZL-012 is a novel molecule that enables de-novo generation of thermogenic
tissue at favorable anatomical sites. As a result, the extra fat accumulated in obese persons
will be turned into heat. This is a double blind, randomized, placebo controlled, dose
escalation Phase 2a clinical trial for the evaluation of safety, efficacy and
thermogenesis-induction of RZL-012 in overweight and obese volunteers. This trial aims to
study the ability of RZL-012 in treating obesity via the induction of thermogenic foci in
subcutaneous fat.

Inclusion Criteria:

1. Adult male subjects, 20-60 years old.

2. Subject is considered overweight and obese, with 27.5 < BMI ≤ 34.9.

3. Significant subcutaneous abdominal fat as defined by Waist to hip ratio (WHR) ≥ 0.9.

4. Subjects with stable weight in the last 3 months by medical history.

5. Not one of the following eating disorders by subject's declaration: anorexia nervosa,
bulimia nervosa.

6. Generally considered healthy according to medical history, physical examination,
electrocardiogram (ECG) and laboratory evaluation with a special emphasis on metabolic
parameters (fasting glucose concentration < 100 mg, normal blood pressure).

7. Subject is willing to refrain from sexual activity or agrees to use a double-barrier
contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with
RZL 012.

8. Subjects must be able to adhere to the visit schedule and protocol requirements and be
available to complete the study.

9. Subjects must sign an informed consent indicating that they are aware of the
investigational nature of the study.

Exclusion Criteria:

1. Subjects weighing less than 75 kg.

2. Subjects who have reduced/gained weight more than 5% of their current body weight in
the last 3 months.

3. Unable to tolerate subcutaneous injection.

4. Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric
disorders, that in the opinion of the investigator put the subject at significant
risk, are not eligible.

5. Subjects who test positive to either Hepatitis B virus (HBV), Hepatitis C virus (HCV),
or Human immunodeficiency virus (HIV) are not eligible.

6. Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune
disease or subjects taking immunosuppressive drugs such as corticosteroids are
ineligible.

7. As a result of medical review, physical examination, the PI (or medically qualified
nominee) considers the subject unfit for the study.

8. Medication use on regular basis.

9. Positive drug and alcohol tests.

10. Known sensitivity to components of the injection formulation.

11. Prior wound, tattoo or infection in the treated area.

12. Excessive growth of hair in the abdomen region.

13. Claustrophobia or MRI incompatible device or implant.