A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study With an Open-Label Extension Evaluating the Efficacy and Safety of VENT-03 in Adult Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Lupus Erythematosus

The goal of this clinical trial is to learn if VENT-03 works to treat patients with cutaneous lupus erythematosus (CLE) who may or may not have systemic lupus erythematosus (SLE). Another goal is to learn about the safety of VENT-03 and how it is processed by the body. The main questions it aims to answer are: * Does VENT-03 affect the activity and severity of CLE? * What side effects do participants have when taking VENT-03? Researchers will compare VENT-03 to a placebo (a look-alike substance that contains no drug) to see if VENT-03 works to treat patients with CLE. Participants will: * Take VENT-03 or a placebo for 4 weeks, then all participants will switch to VENT-03 for another 8 weeks; * Visit the clinic once a month for checkups and tests.

Key Inclusion Criteria: * Cutaneous lupus: * CLASI-A score ≥8; * At least 1 active discoid lupus erythematosus (DLE) lesion, OR at least 1 active subacute CLE lesion * If participant has previous SLE diagnosis: * Positive antinuclear antibody test at Screening by immunofluorescent assay at the central laboratory with titer ≥ 1:80; * Meets the American College of Rheumatology/ European Alliance of Associations for Rheumatology 2019 criteria for SLE; and * Currently receiving at least one of the specified SLE medication treatments, at stable doses. Key Exclusion Criteria: * Meet protocol-specified infection or lab criteria; any other laboratory test results that, in the investigator's opinion, might place participant at unacceptable risk for participating in this study; * Moderate or severe liver impairment as classified by the Child-Pugh criteria (categories B and C); * Has drug-induced lupus, rather than 'idiopathic' lupus; * History of, or current, inflammatory joint or skin disease other than SLE and cutaneous lupus; * Diagnosis of select potentially confounding autoimmune disorders * Active severe or unstable neuropsychiatric SLE; * Hospitalization for a severe lupus flare in the past 3 months, or active severe SLE-driven disease, including lupus nephritis, for which in the opinion of the PI the protocol-specified SOC is insufficient; * History of or current diagnosis of anti-phospholipid syndrome; * History of any non-lupus disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to Day 1; * Meets protocol specified medical history of infectious diseases and infections and/or opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within specified timeframes; * Cancer screening results suspicious of malignancy or history of cancer within time specified with exceptions for curative therapy for squamous or basil cell carcinoma and cervical cancer in situ; and * Meets protocol specified exclusions related to concomitant medications.