Results from a Phase I clinical trial for Hengrui Pharma's investigational dual-target fusion protein SHR-2173 in systemic lupus erythematosus were prominently featured at the 2026 European Alliance of Associations for Rheumatology annual meeting, held in London from June 3 to 6.

The study was a multicenter, open-label, multiple ascending dose Phase I trial designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of SHR-2173 in patients with SLE.

Understanding the Study's Rationale

Systemic lupus erythematosus is a complex and severe autoimmune disease driven by multiple pathological pathways. Two key mechanisms are the abnormal activation of the type I interferon system and the overactivation of the BAFF/APRIL signaling pathway, which promotes the survival of autoreactive B cells.

Current single-target therapies often fail to adequately control the overall disease. SHR-2173 is designed as a fusion protein combining an anti-IFNAR1 antibody with a variant of the TACI receptor protein, aiming to simultaneously block both the type I interferon and BAFF/APRIL pathways.

Study Design and Patient Groups

The trial enrolled 30 Chinese patients with mild to moderate SLE disease activity who were on stable background therapy. Patients were assigned to receive subcutaneous injections of SHR-2173 at doses of 100 mg, 300 mg, or 600 mg once weekly for five consecutive weeks, followed by a 12-week follow-up period.

Key Findings on Safety and Pharmacokinetics

The treatment was generally well-tolerated across all dose groups. Treatment-emergent adverse events were predominantly mild to moderate in severity, with no unexpected safety signals identified and no TEAEs leading to study discontinuation.

Pharmacokinetic analysis showed a nonlinear profile, with the elimination half-life increasing from approximately 8 days in the 100 mg group to 16 days in the 600 mg group.

Observed Pharmacodynamic and Preliminary Efficacy Signals

Pharmacodynamic assessments indicated that SHR-2173 effectively engaged its dual targets. Post-treatment, trends of decreasing serum immunoglobulin levels and interferon gene signature scores were observed, alongside increases in complement C3 and C4 levels, consistent with reduced disease activity.

In patients with a baseline SLEDAI-2K score of 6 or higher, the overall SLE Responder Index 4 response rate was 69%. Improvements were also noted across multiple disease activity measures, including SLEDAI-2K, BILAG-2004, Physician's Global Assessment, and the urine protein-to-creatinine ratio, suggesting broad multi-organ system benefits.

Conclusions and Future Outlook

The Phase I results indicate that SHR-2173 has a favorable safety and tolerability profile, demonstrates supportive pharmacokinetic and pharmacodynamic characteristics for its dual-target mechanism, and shows promising preliminary efficacy signals.

By targeting two core pathological pathways in SLE, SHR-2173 represents a novel therapeutic strategy. These initial clinical findings provide a strong foundation for its continued development, with future Phase II/III studies needed to confirm its long-term efficacy and safety in larger patient populations.