Beeline Medicines Initiates First Trial in Lupus Pivotal Development Program with Global Phase 2/3 DISCOVERY Trial of Afimetoran in Cutaneous Lupus Erythematosus (CLE)

– Afimetoran, an investigational oral, once-daily, equipotent TLR7/8 inhibitor, targets a central driver of lupus biology with the potential to address both cutaneous and systemic disease –

– Global, randomized, double-blind, placebo-controlled, operationally seamless Phase 2/3 DISCOVERY trial will enroll approximately 390 adults with active CLE with or without systemic disease –

– Pivotal program expected to build on clinically meaningful efficacy and favorable safety observed in previous Phase 1b and Phase 2 studies of afimetoran in lupus –

STAMFORD, Conn., Nov. 02, 2026 (GLOBE NEWSWIRE) -- Beeline Medicines Corporation, a clinical-stage biotechnology company focused on developing and delivering category-leading precision therapies to transform the lives of people with autoimmune and inflammatory diseases, today announced the initiation of the first trial of its lupus pivotal development program for afimetoran, with the global Phase 2/3 DISCOVERY trial in cutaneous lupus erythematosus (CLE) now actively enrolling participants. DISCOVERY will evaluate the efficacy and safety of afimetoran compared to placebo in adults with active CLE, with or without systemic lupus. Afimetoran is an investigational selective, oral, once-daily, equipotent small-molecule inhibitor of Toll-like receptors 7 and 8 (TLR7 and TLR8), targets that play complementary and critical roles in lupus pathogenesis.

CLE is a chronic autoimmune skin disease that can have a profound impact on quality of life, with lesions that can cause pain, permanent scarring, and hair loss. CLE disproportionately affects women in their childbearing years and people of color. There are currently no approved targeted therapies for CLE, and many patients do not achieve adequate disease control with current therapies, which rely largely on antimalarials, topical and systemic corticosteroids, and immunosuppressants.

“Cutaneous disease is among the most visible and distressing aspects of lupus, yet there are no approved targeted therapies for people living with CLE,” said Saqib Islam, Chief Executive Officer of Beeline Medicines. “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.”

“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.”

The DISCOVERY trial will build on the results of the exploratory Phase 1b study in CLE, where afimetoran showed encouraging preliminary clinical activity and was generally well tolerated, with improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score accompanied by rapid and sustained reductions in type I interferon and TLR7/8 gene signatures. These pharmacodynamic effects were evident as early as Week 1 and sustained through the duration of the treatment period.

Afimetoran’s potential as a treatment for CLE is further supported by improvements in CLASI observed in the global Phase 2 study in systemic lupus erythematosus (SLE), which enrolled a subgroup of patients with concomitant cutaneous manifestations. Positive topline results were announced in September 2026, and additional data from the Phase 2 SLE study will be presented in a late-breaking oral presentation at American College of Rheumatology (ACR) Convergence 2026 on November 11, 2026. As part of its lupus pivotal program, Beeline Medicines also plans to advance afimetoran into Phase 3 development in SLE in 2027.

“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,” said Albert T. Roy, President and CEO of the Lupus Research Alliance. “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.”

About the Phase 2/3 DISCOVERY Trial
DISCOVERY (NCT07881120) is a global, randomized, double-blind, placebo-controlled Phase 2/3 trial evaluating the efficacy, safety, and tolerability of afimetoran in approximately 390 adults with active CLE, with or without systemic manifestations, who are refractory and/or intolerant to antimalarial therapy. The trial is being conducted in two stages under a single, operationally seamless protocol. Stage 1 (Phase 2) compares two doses of afimetoran with placebo for 24 weeks, on top of participants’ existing standard-of-care lupus therapy, with results informing dose selection for Stage 2. Stage 2 (Phase 3) compares the selected dose of afimetoran with placebo for 24 weeks to confirm efficacy and safety. All participants will then receive afimetoran for an additional 28 weeks, for a total study treatment period of 52 weeks.

The primary endpoint of Stage 1 (Phase 2) is percent change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) total score at Week 24. The primary endpoint of Stage 2 (Phase 3) is the proportion of participants achieving a CLASI-70 response (≥70% decrease from baseline in CLASI-A total score) at Week 24. Additional endpoints assess other CLASI-A response measures, investigator- and patient-reported skin disease measures, quality of life, systemic disease activity, and safety.

For more information about the DISCOVERY trial, please visit www.clinicaltrials.gov.¹

About Afimetoran
Afimetoran is an investigational selective, oral, once-daily, equipotent small-molecule inhibitor of Toll-like receptors 7 and 8 (TLR7 and TLR8), targets that play complementary and critical roles in lupus pathogenesis. Human genetics directly implicate TLR7 as a disease driver in lupus, while the biology of TLR8 contributes to pro-inflammatory cytokine production and immune responses, leading to potential progressive disease activity and irreversible organ damage.^2-7 By blocking these components of the immune cascade, afimetoran has been shown to rapidly and substantially suppress signaling pathways in innate immune cells and B cells implicated in the pathology of various autoimmune diseases, including systemic and cutaneous lupus erythematosus.^8-12 Afimetoran was a discovery by Bristol Myers Squibb’s researchers and was licensed to Beeline Medicines in July 2025. Afimetoran was granted Fast Track designation by the U.S. Food and Drug Administration for systemic lupus erythematosus in May 2025.

About Lupus 
Lupus encompasses a spectrum of chronic, heterogeneous autoimmune conditions marked by immune dysregulation, autoantibody production, and inflammation that can affect multiple organ systems.¹³ More than 5 million people worldwide live with a form of lupus, which disproportionately affects women of childbearing age (approximately 90% of people living with lupus are women) and individuals of Black, Hispanic, Asian, and Indigenous ancestry, in whom the disease tends to begin earlier, damage organs more rapidly, and lead to worse outcomes.^13,14 Its principal forms, including systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), and lupus nephritis (LN), which reflects renal involvement in SLE, may overlap along the disease continuum. Up to 85% of people with SLE develop cutaneous manifestations.¹⁵ While up to 25% of patients initially diagnosed with CLE may progress to SLE over time, not all patients presenting with CLE will develop systemic disease.^15,16 

SLE is the most common form of lupus and includes the most severe manifestations, characterized by multi-organ involvement and a relapsing-improving course of episodic flares that can cause cumulative, irreversible organ damage and significant morbidity.^17,18 CLE comprises inflammatory skin conditions that can occur alone or alongside systemic disease, with lesions that range from localized to widespread and can lead to profound impact on quality of life and lasting scarring and dyspigmentation in discoid lupus.^19,20 Despite recent advances, an urgent unmet need remains for well-tolerated, oral targeted therapies that deliver durable disease control with reduced steroid exposure.^17,21 

About Beeline Medicines
Beeline Medicines is a clinical-stage biotechnology company focused on developing and delivering category-leading precision therapies to transform the lives of people living with autoimmune and inflammatory diseases. With a portfolio of potential best-in-class and first-in-disease therapeutic candidates that directly target key pathways governing dysregulated immunological and inflammatory responses, the Company is developing medicines that have the opportunity to provide durable, life-changing impact. Led by an established executive team and backed by world-class life science investors, each day Beeline Medicines is determined to bring the scientific rigor and operational excellence to get to what matters for patients – realizing a world where people with immune-mediated diseases can live life fully.

Beeline Medicines is headquartered in Stamford, Connecticut, with additional operations in Cambridge, Massachusetts, and Durham, North Carolina. For more information, visit www.BeelineMedicines.com and follow on LinkedIn.

Beeline Medicines Contact Information
Samantha Sandler
Head of Communications and Investor Relations

Media:
media@beelinemedicines.com 

Investors:
investors@beelinemedicines.com 

References
¹ ClinicalTrials.gov. NCT07881120. Available at: https://clinicaltrials.gov/study/NCT07881120. 
² Bender AT et al. Immunohorizons. 2020;4(2):93–107. 
³ Brown GJ et al. Nature. 2022;605(7909):349–356. 
⁴ Vinuesa CG et al. Nat Rev Rheumatol. Published online June 19, 2026. doi:10.1038/s41584-026-01388-0. 
⁵ Maz MP et al. J Autoimmun. 2022;132:102865. 
⁶ Skenteris NT et al. JCI Insight. 2026. doi:10.1172/jci.insight.187422.
⁷ Klein B et al. Nat Rev Rheumatol. 2025;21(12):703–718.
⁸ Hosein F et al. ACR Open Rheumatol. 2025;7(7):e70059. 
⁹ Maz MP, Kahlenberg J M. Curr Opin Rheumatol. 2020;32(6):583–589. 
¹⁰ Larosa M et al. Exp Biol Med (Maywood). 2019;244(1):42–51. 
¹¹ Mende R et al. Front Immunol. 2018;9:1250. 
¹² Rzeszotarska E et al. Clin Exp Rheumatol. 2022;40:1708–1717. 
¹³ Lupus Foundation of America. Lupus facts and statistics. https://www.lupus.org/resources/lupus-facts-and-statistics. 
¹⁴ Somers E et al. Arthritis Rheumatol. 2014;66(2):369–378.  
¹⁵ Stull C et al. J Rheumatol. 2023;50(1):27–35.
¹⁶ Zhou W et al. Expert Rev Clin Immunol. 2020;16(8):829–837.
¹⁷ Hoi A et al. Lancet. 2024;403(10441):2326–2338. 
¹⁸ Kaul A et al. Nat Rev Dis Primers. 2016;2:16039. 
¹⁹ Drenkard C et al. Front Med (Lausanne). 2022;9:897987. 
²⁰ Verma SM et al. Br J Dermatol. 2014;170(2):315–321.
²¹ Fanouriakis A et al. Ann Rheum Dis. 2024;83(1):15–29.