Expanded Access Metreleptin Study

Leptin is a naturally occurring hormone and an important regulator of energy homeostasis and
other diverse physiological functions. Circulating levels of leptin closely correlate with
the amount of adipose tissue present. Metreleptin, a recombinant analogue of human leptin, is
a 147-amino acid polypeptide that differs from the human leptin sequence by 1 additional
amino acid, methionine, located at the amino-terminal end. Metreleptin has the same
physiological effects as leptin, including regulation of energy homeostasis and metabolic
function.

The patient group covered under this expanded access submission has demonstrated evidence of
clinical benefit from treatment with metreleptin in clinical study FHA101/MB002-002, and
needs expanded access to continue treatment without interruption.

Inclusion Criteria:

1. Signed Written Informed Consent

a) Before any program procedures are performed, the details of the program will be
described to the patient and the patient will be given a written informed consent
document to read. If the patient agrees to participate in the program, consent will be
indicated by signing and dating of the informed consent document in the presence of
program personnel.

2. Target Population

1. Ability to comply with visits and procedures required by program

2. Previously enrolled in study FHA101/MB002-002

3. Has physician-confirmed partial lipodystrophy and had evidence of benefit with
metreleptin treatment based on the following metabolic criteria demonstrated
within the last year of metreleptin treatment (if on treatment over 1 year) from
baseline values:

- TG reduction ≥ 30% OR

- HbA1c reduction ≥ 1% OR

- Decrease in insulin requirements ≥ 40% OR

- Decrease in episodes of pancreatitis OR

- Improvement in steatohepatitis OR

- Withdrawal of metreleptin led to marked worsening of metabolic parameters

3. Age and Reproductive Status

1. Male or female, over the age of 6 months

2. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
hours prior to the restart of study drug.

3. Women must not be breastfeeding

4. WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with metreleptin plus 5 half-lives of metreleptin plus 30
days (duration of ovulatory cycle) for a total of 6 months post-treatment
completion.

5. Men who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with metreleptin plus 5
half-lives of the metreleptin plus 90 days (duration of sperm turnover) for a
total of 3 months post-treatment completion.

Exclusion Criteria:

1. Target Disease Exceptions

a) Has acquired lipodystrophy and clinically significant hematologic abnormalities
(such as neutropenia and/or lymphadenopathy)

2. Medical History and Concurrent Diseases

1. Has been diagnosed with generalized lipodystrophy

2. Has been diagnosed with HIV infection

3. Has a clinically significant medical condition that could potentially affect the
risk/benefit ratio for metreleptin treatment and/or the personal well-being of
the patient, as judged by the primary treating physician

4. Has known infectious liver disease

5. Has known allergies to E. coli-derived proteins or hypersensitivity to any
component of metreleptin treatment

3. Other Exclusion Criteria

1. Prisoners or patients who are involuntarily incarcerated.

2. Patients who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.