A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED)

Open to people ages 18 years and up

for Healthy Volunteers:

• Must be free of clinically significant disease or medical conditions as determined by the Investigator
• Female volunteers must not be of child-bearing potential

for Healthy Volunteers:

∙ Must not have a history of or any evidence of diabetes mellitus, recently diagnosed renal impairment or inflammatory bowel disease, or clinically significant ear pathology or earing impairment

Key Inclusion Criteria for Participants with TED in Phase 1/2 MAD cohorts:

• Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 1 year prior to screening OR moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began over 1 year prior to screening
• Must have active TED and a Clinical Activity Score (CAS) of ≥ 4 on the 7-item scale for the study (more proptotic) eye OR chronic TED with no CAS requirement
• Must agree to use highly effective contraception as specified in the protocol
• Female TED participants must have a negative serum pregnancy test

Key Exclusion Criteria for Participants with TED in Phase 1/2 MAD cohorts:

• Must not have received prior treatment with another anti-IGF-1R monoclonal antibody
• Must not have used oral corticosteroids within 4 weeks prior to Day 1
• Must not have received rituximab, tocilizumab or other immunosuppressive agents within 90 days prior to Day 1
• Must not have evidence of optic nerve involvement within the previous 6 months
• Must not have corneal decompensation in the study eye unresponsive to medical management
• Must not have had previous orbital irradiation or surgery for TED in the study eye
• Must not have a history inflammatory bowel disease Must not have clinically significant ear pathology or hearing impairment
• Must not have received an investigational agent for any condition within 60 days
• Female TED participants must not be pregnant or lactating

Key Inclusion Criteria for Participants with TED in Phase 3 study:

• Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 15 months prior to screening
• Must have Clinical Activity Score (CAS) of ≥ 3 on the 7-item scale for the study (more proptotic) eye
• Must agree to use highly effective contraception as specified in the protocol
• Female TED participants must have a negative serum pregnancy test

Key Exclusion Criteria for Participants with TED in Phase 3 study:

• Must not have received prior treatment with another anti-IGF-1R monoclonal antibody
• Must not have used oral corticosteroids within 2 weeks prior to Day 1
• Must not have received rituximab, tocilizumab or other immunosuppressive agents within 8 weeks prior to Day 1
• Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results
• Must not have had previous orbital irradiation or surgery for TED in the study eye
• Must not have a history inflammatory bowel disease
• Must not have a history or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing l loss
• Must not have received an investigational agent for any condition
• Female TED participants must not be pregnant or lactating