Beeline Medicines, a Stamford biotechnology company, began enrolling participants in a global Phase 2/3 trial of afimetoran, an investigational oral, once-daily therapy for cutaneous lupus erythematosus (CLE), a chronic autoimmune skin disease.
There are no approved targeted therapies for CLE, which can cause pain, permanent scarring and hair loss. Current therapies rely largely on antimalarials, corticosteroids and immunosuppressants.
The DISCOVERY trial is randomized, double-blind and placebo-controlled, and will enroll approximately 390 adults with active CLE who are refractory or intolerant to antimalarial therapy. Participants will receive placebo or afimetoran for 24 weeks in each of two stages, then afimetoran for 28 more weeks, for a total treatment period of 52 weeks. Saqib Islam, chief executive officer of Beeline Medicines, said: “Cutaneous disease is among the most visible and distressing aspects of lupus, yet there are no approved targeted therapies for people living with CLE. Afimetoran has shown meaningful clinical activity in skin manifestations of lupus across multiple studies to date, and DISCOVERY represents a critical step toward demonstrating its potential, as a once-daily oral therapy, to transform treatment for millions of people impacted by this devastating disease. With DISCOVERY, we are excited to launch our pivotal development program spanning cutaneous and systemic lupus and to begin generating the late-stage clinical evidence required to bring afimetoran to the people who need it.”
Afimetoran inhibits two immune receptors, Toll-like receptors 7 and 8, and was discovered by Bristol Myers Squibb researchers before Beeline licensed it in July 2025.
“DISCOVERY’s seamless Phase 2/3 design enables us to move from dose selection to confirmatory evidence under a single protocol, allowing us to assess afimetoran’s therapeutic potential as efficiently as possible knowing that CLE patients are waiting for effective, well-tolerated oral targeted therapies,” said Nathalie Franchimont, M.D., Ph.D., chief medical officer of Beeline Medicines, “Importantly, the trial is enrolling participants with CLE with or without systemic involvement, representing a broad range of patients who urgently require new therapeutic advances. We are grateful to the investigators and participants joining us in this study.”
An earlier Phase 1b study in CLE showed improvements in a skin disease severity score, and topline results from a Phase 2 study in systemic lupus were announced in September.
Albert T. Roy, president and chief executive officer of the Lupus Research Alliance, said: “Cutaneous lupus erythematosus can impact nearly every part of a person’s life – from how they see themselves to how they connect with others. Its visible, recurring symptoms can leave lasting scars, both physical and emotional. Partnering with people who live with this disease is critical, and we appreciate that Beeline Medicines actively engaged the lupus community, through our clinical affiliate, Lupus Therapeutics, in the design of the DISCOVERY trial. The initiation of this trial is important, and we look forward to following afimetoran’s progress through the clinical development process.”
Beeline plans to advance afimetoran into Phase 3 development in systemic lupus in 2027 as part of its lupus pivotal program.
