Zura Bio Limited shared supportive data from a Phase 1 study evaluating its lead candidate, tibulizumab (ZB-106), for the treatment of Sjogren?s syndrome. These data, along with preclinical data supporting further development of tibulizumab in rheumatoid arthritis (RA), were presented at the Annual European Congress of Rheumatology (EULAR) 2024 in Vienna. The randomized, double-blind, placebo-controlled Phase 1 study evaluated four ascending doses of tibulizumab in 25 participants with Sjogren?s syndrome.

Twenty-one participants in the 12-week study received =1 dose of tibulizumab (30mg Q4W, 100mg Q4W, 300mg Q4W, 300mg Q2W), with four receiving placebo. Treatment with tibulizumab was generally well tolerated in patients with Sjogren?s syndrome. Serum levels of total IL-17A and BAFF increased following tibulizumab administration, reflecting target engagement.

At doses of 100 mg Q4W and higher, the total IL-17A and BAFF concentrations appeared to plateau, suggesting the targets were engaged nearly to maximum levels. Throughout the study, total B cell counts were dose-dependently reduced in all participants, while administration of tibulizumab was associated with lower levels of Th1 cells. Tibulizumab was also shown to modulate inflammatory mediators, including serum amyloid A, interleukins 5 and 10, as well as basic fibroblast growth factor.

These reductions suggest tibulizumab has treatment potential for additional autoimmune conditions. The preclinical study was designed to evaluate the respective and combined benefits of inhibiting IL-17A and BAFF in a mouse model of RA. Mice received IL-17A antibodies and/or BAFF antibodies, or a control antibody.

Cumulative clinical disease scores were significantly reduced in mice treated with the combination of anti-IL-17A and anti-BAFF compared to the isotype control (p<0.001); combined IL-17A and BAFF inhibition also resulted in less signs of disease compared to individually targeted treatment. Combined IL-17A and BAFF inhibition reduced inflammation significantly compared to the control (p<0.05). Combined IL-17A and BAFF inhibition was associated with a significant reduction of anti-collagen antibodies compared to the control (p<0.01).

Tibulizumab, a humanized bispecific dual antagonist antibody, is a fusion of TALTZ® (ixekizumab) and tabalumab that has been engineered to bind to and neutralize both IL-17A and BAFF. Tibulizumab is expected to enter Phase 2 clinical development for the treatment of systemic sclerosis in Q4-2024 and hidradenitis suppurativa in Q2-2025. Completed tibulizumab studies include Phase 1/1b trials in Sjogren?s syndrome and rheumatoid arthritis.