1. Adults aged ≥18 years (or ≥16 years where permitted).
2. Histologically confirmed active cutaneous lupus erythematosus (CLE) with or without systemic manifestations.
3. Active subacute and/or chronic cutaneous lupus erythematosus, including discoid lupus erythematosus.
4. Moderate to severe skin disease activity.
5. Refractory, intolerant, or inadequately controlled on antimalarial therapy.
6. Willing and able to comply with study requirements.
7. Agreement to protocol-specified contraception requirements
You may not be if
1. Severe lupus nephritis or severe neuropsychiatric SLE
2. Drug-induced lupus
3. Active or chronic clinically significant infections, including HIV, hepatitis B, hepatitis C, active tuberculosis, untreated latent tuberculosis, or uncontrolled congestive heart failure
4. Significant concurrent autoimmune disease other than lupus-related conditions permitted by the protocol
5. Active malignancy or recent history of certain cancers
6. Other dermatologic conditions that may interfere with study assessments
7. Recent use of prohibited medications or investigational therapies
8. Prior treatment with afimetoran or another TLR7/TLR8 antagonist
9. Clinically significant laboratory abnormalities or severe organ dysfunction
