1. Updated the SAE reporting procedure to enter the information into the eCRF and email/fax the information only if the site was unable to access the eCRF to ensure the Sponsor had access to the information; 2. Added efficacy evaluations (CAS and Clinical Measures of Severity [including proptosis]) to Weeks 36, 48 and 60 in order to identify relapsed subjects at earlier time points in the study; 3. Added pregnancy tests to Week 48 for women of childbearing potential, and increased the contraception requirement and the pregnancy reporting period (for both men and women) from 90 days to 180 days due to the teratogenic effects of teprotumumab noted in a monkey embryo-fetal development toxicity study. Based on the Week 24 plasma exposures demonstrated in a previous study (TED01RV), the 6-month waiting period would allow sufficient time for plasma concentrations to decrease to levels that would reduce the risk of teratogenicity; 4. Specified that any planned corrective surgery/irradiation over the course of the study was not allowed (Inclusion Criterion #7) in order not to interfere with interpretation of the efficacy results; 5. Added post-infusion vital signs to Week 3 (second infusion of study drug) as an added safety precaution; 6. Clarified/updated AEs requiring permanent discontinuation from the study: • Subjects with any drug-related anaphylactic reaction were to be discontinued from the study; • Provided a laboratory cutoff value for hyperglycemia; • Added diagnosed or suspected inflammatory bowel disease (diagnosed or suspected inflammatory bowel disease was already an exclusion criterion), as exacerbation of underlying inflammatory bowel disease by teprotumumab could not be excluded at that time; 7. Clarified the definition of an overdose to be 5% or more than the assigned dose;

(continued) 8. Added Bioclinica eClinical Solutions IWRS contacts prior to dosing for each scheduled infusion (Weeks 3, 6, 9, 12, 15, 18 and 21) in addition to Day 1, as Bioclinica was also responsible for clinical supply inventory management. Also added IWRS contacts at Screening and the Week 24 Visit to register the Screening and End-of-Treatment Visits; 9. Clarified that the volume of study drug to be administered was determined by the IWRS and not the site pharmacist; 10. Added that any subject testing positive for ADA (after confirmatory and reactive titer testing) was tested for NAb. Subjects positive for NAb (not those positive for ADA) were to be followed until levels either reverted to Baseline or the subject’s value decreased or remained stable; and 11. Other minor typographical errors, omissions and clarifications.

1. Incorporated the changes of Protocol Version 1.1; 2. Updated the contract research organization name (from INC Research to Syneos Health) and address; 3. Increased the upper age limit from 75 to 80 years; 4. Clarified that the exclusionary changes in proptosis and CAS between Screening and Baseline refers only to the study eye; 5. Amended and clarified restrictions on previous and planned use of corticosteroids for the treatment of TED and non-TED conditions; 6. Excluded subjects with human immunodeficiency virus, hepatitis C, or hepatitis B infections; 7. Added restrictions on the use of non-steroid eye drops during the study; 8. Added ‘or designee’ to the unmasked pharmacist role in the study where allowed by institutional policy and local regulations; 9. Clarified that used and partially used drug vials were to be retained at the investigative site only if permitted by site policy; and 10. Updated the status of the Investigator’s Brochure from in progress to completed.

1. Added diplopia responder rate (defined as the percentage of subjects with Baseline diplopia >0 in study eye who have a reduction of ≥1 grade with no corresponding deterioration [≥1 grade worsening] in the fellow eye at Week 24) as a secondary endpoint; 2. Added 2 additional follow-up contacts (telephone or email) at 6 and 12 months after the Week 72 Visit to assess any additional TED treatment received since last study contact; 3. Clarified that female subjects of childbearing potential who were sexually active with a non-vasectomized male partner must have agreed to use 2 reliable forms of contraception, one of which was recommended to be hormonal, during the trial and for 180 days after the last dose of study drug; 4. Clarified that male subjects who were sexually active with a female partner of childbearing potential must have agreed to use a barrier contraceptive method from Screening through 180 days after the last dose of study drug; 5. Changed the number of teprotumumab doses administered in the open-label extension study (HZNP-TEP-302) from “up to 8” to ‘8’. 6. Clarified that the CAS criteria for determining relapse refers only to the study eye; 7. Amended the CAS relapse criterion to include an increase in CAS of ≥2 points since Week 24 with an absolute CAS ≥4 following the Week 24 Visit; 8. Specified the minimum duration of study drug infusions; 9. Clarified that the weight obtained at Week 12 could be used for the calculation of study drug dose beginning at Week 12 or Week 15; 10. Removed the specified temperature collection methods (oral or tympanic); 11. Corrected that the urine sample collected at Week 15 was for pregnancy testing only; 12. Changed the definition of the end of the trial to date of the last subject contact at Week 120; 13. Updated statistical analysis methods; 14. Updated Sponsor Representative title; and 15. Corrected minor typographical errors.