Beeline Medicines Announces Presentation of Phase 2 Results of Afimetoran in Systemic Lupus Erythematosus at ACR Convergence 2026

– All three afimetoran doses met the primary endpoint with a placebo-adjusted difference in SRI-4 response of more than 30 percentage points at Week 48 (p<0.001 for all doses) –

– Secondary endpoints were directionally consistent with the primary endpoint and demonstrated improvements in skin, joints, steroid sparing, and quality-of-life measures –

– Afimetoran was generally well tolerated over 48 weeks, with most adverse events classified as mild to moderate and no new safety signals observed –

STAMFORD, Conn., Nov. 11, 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 detailed results from its global Phase 2 study of afimetoran, an investigational oral, once-daily, equipotent inhibitor of Toll-like receptors 7 and 8 (TLR7 and TLR8), in adults with active, moderate-to-severe systemic lupus erythematosus (SLE). The data are being presented today at 9:00 AM EST in a late-breaking oral presentation at the American College of Rheumatology (ACR) Convergence 2026 in Orlando, Florida.

The Company previously reported that the Phase 2 study met its primary endpoint, with all three afimetoran doses demonstrating a greater than 30 percentage-point difference in SLE Responder Index-4 (SRI-4) response rates versus placebo at Week 48 (p<0.001), and that secondary endpoints were generally consistent with the primary endpoint. The detailed results being presented today expand on these findings with new data on the study population, physician- and patient-reported outcomes, additional safety details, and disease biomarker measurements through Week 48.

“In my years of caring for people with lupus, I’ve seen how pain and disease activity can make it hard to work, care for family, or simply get through the day. That is why there is a clear need for well-tolerated and effective oral treatment options,” said Kenneth C. Kalunian, M.D., Professor of Medicine at the University of California, San Diego School of Medicine, Wolfe Family Director of the UC San Diego Lupus Center of Excellence, lead author of the study, and presenting author at ACR. “In the Phase 2 study in SLE, participants treated with afimetoran had substantially higher SRI-4 response rates than placebo at every dose, with consistent improvements in secondary endpoints evaluating skin and joint involvement, symptoms my patients raise at nearly every visit. These results make me optimistic about what an oral TLR7/8 inhibitor could potentially offer, and I’m glad to share them with the lupus community today.”

Beeline Medicines plans to advance afimetoran into Phase 3 development in SLE in 2027 as part of its lupus pivotal development program, which recently launched with the initiation of the global Phase 2/3 DISCOVERY trial in cutaneous lupus erythematosus (CLE) (NCT07881120). DISCOVERY, which is now actively enrolling participants, will evaluate the efficacy and safety of afimetoran compared with placebo in adults with active CLE, with or without systemic lupus.

“These are among the most compelling Phase 2 data generated in lupus, with consistent results across every dose and endpoint evaluated, reinforcing our belief that afimetoran has the potential to become a foundational treatment across the lupus spectrum, from cutaneous to systemic disease,” said Saqib Islam, Chief Executive Officer of Beeline Medicines. “We have launched our lupus pivotal development program with the Phase 2/3 DISCOVERY trial of afimetoran in cutaneous lupus, and with these Phase 2 results in hand, we plan to begin Phase 3 development in SLE in 2027, bringing us closer to delivering a potential once-daily oral treatment option for people living with this chronic disease.”

Phase 2 Study Design, Demographics, and Baseline Characteristics
The Phase 2 study randomized 248 participants 1:1:1:1 to receive afimetoran 2.5 mg, 10 mg, 30 mg, or placebo for 48 weeks, in addition to protocol-permitted background standard of care medications, including corticosteroids with a mandatory taper. The primary endpoint was the proportion of participants achieving SRI-4 response at Week 48.

Baseline characteristics for all study participants reflected an adult population with active, moderate-to-severe SLE. Participants had a mean age of 41.6 years, 93.5% were female, and the mean hybrid SLE Disease Activity Index (hSLEDAI) score was 10.7, with 66.7% of participants with available biomarker data having high type I interferon levels at baseline. At baseline, 81.5% of participants were receiving oral or systemic corticosteroids, and 83.9% were receiving antimalarials.

Approximately 80% of afimetoran-treated participants completed 48 weeks of treatment, compared with 69.4% of placebo-treated participants. Treatment compliance exceeded 94% in afimetoran-treated arms.

Efficacy
All three afimetoran doses met the primary endpoint, with SRI-4 response rates at Week 48 of 67.8%, 64.1%, and 66.1% for the 2.5 mg, 10 mg, and 30 mg doses, respectively, compared with 34.4% for placebo, corresponding to placebo-adjusted differences of 30.2-31.5 percentage points after adjustment for randomization strata (p<0.001 for each dose).

Secondary endpoints at Week 48 were directionally consistent with the primary endpoint. Response rates on the BILAG-based Composite Lupus Assessment (BICLA), which requires improvement in every organ system with moderate or severe activity at baseline, were 38.7-50.8% across afimetoran doses, compared with 27.9% for placebo. Lupus Low Disease Activity State (LLDAS), which combines low disease activity with a corticosteroid dose of no more than 7.5 mg/day, was achieved by 35.6-39.1% of afimetoran-treated participants, compared with 21.3% for placebo. In addition, 71.9-75.0% of afimetoran-treated participants reached or maintained a corticosteroid dose of ≤7.5 mg/day, compared with 50.0% for placebo. This is an important treatment goal in SLE, as long-term corticosteroid exposure is associated with potential cumulative organ damage.

On secondary measures of skin and joint involvement, afimetoran-treated participants also had numerically higher response rates than placebo at Week 48. Among participants with active skin disease at baseline, defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI-A) of 10 or higher, more than half of afimetoran-treated participants achieved CLASI-50, defined as at least a 50% improvement in the CLASI-A, with response rates of 57.1-66.7% compared with 21.4% for placebo. Among participants with six or more active joints at baseline, 61.0-77.1% of those treated with afimetoran achieved Joint-50, defined as at least a 50% reduction in active joint count, compared with 42.9% for placebo. The skin findings build on prior Phase 1b data in cutaneous lupus erythematosus (CLE) and support the ongoing Phase 2/3 DISCOVERY trial of afimetoran in CLE.

Physician- and patient-reported secondary endpoints also favored afimetoran, with numerically greater improvements than placebo at Week 48 in Physician Global Assessment (PGA) and SF-36 Physical Component Summary scores. Differences from placebo on both measures exceeded thresholds generally considered clinically meaningful (0.3 points in PGA and 2.5 points in SF-36 Physical Component Summary score),¹ indicating benefit perceived by both physicians and patients.

Safety
All doses of afimetoran were generally well tolerated over 48 weeks, with no new safety signals identified across reported adverse events, laboratory results, or ECG parameters; most adverse events were mild to moderate in severity and were comparable across all three dose levels evaluated. Overall rates of treatment-emergent adverse events were 86.6% for all afimetoran-treated participants compared with 79.0% for placebo. Severe treatment-emergent adverse events occurred in 3.2% of all afimetoran-treated participants compared with 9.7% for placebo. Infections were the most common treatment-emergent adverse events, occurring in 60.2% of all afimetoran-treated participants compared with 53.2% for placebo. Serious infections, a key consideration for immunomodulatory therapies in lupus, occurred in 0-3.2% across doses compared with 4.8% for placebo.

Treatment-emergent serious adverse events occurred in 5.9% of afimetoran-treated participants vs. 12.9% for placebo, and treatment-emergent adverse events leading to discontinuation in 3.2% vs. 9.7%. Drug-related treatment-emergent serious adverse events occurred in 1.1% of afimetoran-treated participants vs. 6.5% for placebo, and no deaths occurred in the study.

Biomarkers
In exploratory biomarker analyses, afimetoran demonstrated a downstream inhibition of type I interferon, consistent with TLR7/8 inhibition, and shifted established markers of lupus disease activity toward normal levels. Afimetoran rapidly suppressed the type I interferon gene score, a measure of a pathway central to lupus pathogenesis, at all three doses. Near-maximal suppression was seen at the first assessment at Week 2 and was sustained over the full duration of treatment up to Week 48 across all three doses. Among participants with abnormal levels at baseline, afimetoran was also associated with decreases in anti-double-stranded DNA (anti-dsDNA) autoantibodies and increases in complement C3 and C4 toward the normal range.

“Lupus has long been a challenging disease to demonstrate clear treatment effects, which makes these results especially encouraging,” said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Beeline Medicines. “The consistency we observed across clinical endpoints, together with suppression of type I interferon and changes in key biomarkers of disease activity, gives us a compelling scientific rationale to pursue the late-stage clinical development of afimetoran, an equipotent TLR7/8 inhibitor, in lupus. This study was made possible by its participants, their families, and the investigators and their staff, and we are committed to carrying this work forward into pivotal development.”

Presentation Details
Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Afimetoran, an Oral, Once-Daily Equipotent TLR7/8 Inhibitor, in Participants with Active Systemic Lupus Erythematosus
Session: Late-Breaking Abstract Oral Session, Abstract LB23
Presenter: Kenneth C. Kalunian, M.D., University of California, San Diego
Date/Time: Wednesday, November 11, 2026, 9:00–9:15 AM EST

A copy of the presentation will be available in the Presentations & Publications section of the Beeline Medicines website at BeelineMedicines.com.

About the Phase 2 Study of Afimetoran in Systemic Lupus Erythematosus
The Phase 2 study (NCT04895696) is a global, double-blind, randomized, dose-ranging, placebo-controlled trial evaluating the efficacy, safety, and tolerability of investigational afimetoran in 248 adults with active systemic lupus erythematosus (SLE). The trial enrolled adults aged 18 to 70 years with active moderate-to-severe SLE despite ongoing background treatment. Participants were randomized 1:1:1:1 to receive once-daily oral afimetoran at 1 of 3 dose levels or placebo through Week 48, in addition to protocol-permitted background standard of care medications, including corticosteroids with a mandatory corticosteroid taper. The primary endpoint assessed SLE Responder Index-4 (SRI-4) response at Week 48. Secondary endpoints assessed measures of disease activity including BICLA and low disease activity, skin and joint manifestations, corticosteroid reduction, physician global assessment, and quality of life.²

About the Phase 2/3 DISCOVERY Trial of Afimetoran in Cutaneous Lupus Erythematosus
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.³

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.^4-9 Blocking these components of the immune cascade 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.^10-14 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. Afimetoran is not approved for any use in any country, and its safety and efficacy have not been established.

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.¹⁵ 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.^15,16 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.¹⁷ 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.^17,18

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.^19,20 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.^21,22 Despite recent advances in lupus treatment, substantial unmet medical needs remain, including the burden of persistent disease activity, treatment-related adverse effects, and long-term organ damage.^19,23

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:
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Investors:
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² ClinicalTrials.gov. NCT04895696. Available at: https://clinicaltrials.gov/study/NCT04895696
³ ClinicalTrials.gov. NCT07881120. Available at: https://clinicaltrials.gov/study/NCT07881120
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