Expanded Access Protocol of Teprotumumab (HZN-001) for Patients With Active Thyroid Eye Disease

Inclusion Criteria:

1. Written informed consent.

2. Male or female patient at least 18 years old.

3. Clinical diagnosis active TED with a CAS ≥ 4 (on the 7-item scale).

4. Moderate-to-severe active TED (not sight-threatening but has an appreciable impact
on daily life), usually associated with one or more of the following: lid retraction
≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal
for race and gender, and/or inconstant or constant diplopia.

5. Onset of Active TED symptoms (as determined by patient records) within approximately
12 months prior to eligibility review.

6. Patients must be euthyroid with the baseline disease under control or have mild
hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine
[FT3] levels < 50% above or below the normal limits) at Eligibility review. Every
effort should be made to correct the mild hypo- or hyperthyroidism promptly and to
maintain the euthyroid state for the full duration of participation.

7. Does not require immediate surgical ophthalmological intervention.

8. Diabetic patients must have well-controlled stable disease (defined as HbA1c <
9.0%).

9. Women of childbearing potential (including those with an onset of menopause <2
years, non-therapy-induced amenorrhea for <12 months, or not surgically sterile
[absence of ovaries and/or uterus]) must have a negative serum pregnancy test within
3 weeks prior to the first infusion and negative urine pregnancy tests at all
protocol-specified timepoints (i.e., prior to each infusion); patients who are
sexually active with a non-vasectomized male partner must agree to use 2 reliable
forms of contraception during the expanded access program, one of which is
recommended to be hormonal, such as an oral contraceptive. Hormonal contraception
must be started at least one full cycle prior to the first infusion and continue for
180 days after the last dose of investigational drug. Highly effective contraceptive
methods (with a failure rate less than 1% per year), when used consistently and
correctly, includes implants, injectables, combined oral contraceptives, some
intrauterine devices (IUDs), sexual abstinence or vasectomized partner.

10. Male patients must be surgically sterile or, if sexually active with a female
partner of childbearing potential, must agree to use a barrier contraceptive method
from the first infusion through 180 days after the last dose of investigational
drug.

11. Patient is willing and able to comply with the prescribed treatment protocol and
evaluations for the duration of their participation.

Exclusion Criteria:

1. Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the
first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6
months prior to the first infusion of teprotumumab. Use of any other non-steroid
immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.

2. Use of an investigational agent for any condition within 60 days prior to the first
infusion or anticipated use during the course of the protocol.

3. Pregnant or lactating women.

4. Biopsy-proven or clinically suspected IBD (e.g., diarrhea with or without blood or
rectal bleeding associated with abdominal pain or cramping/colic, urgency, tenesmus,
or incontinence for more than 4 weeks without a confirmed alternative diagnosis OR
endoscopic or radiologic evidence of enteritis/colitis without a confirmed
alternative diagnosis).

5. Known hypersensitivity to any of the components of teprotumumab or prior
hypersensitivity reactions to mAbs.

6. Any other condition that, in the opinion of the Sponsor, would preclude inclusion in
the expanded access program.

7. Previous enrollment in this study or participation in a prior teprotumumab clinical
study.

8. Human immunodeficiency virus, hepatitis C or hepatitis B infections.