Zura Bio Shares Tibulizumab Data at EULAR 2024

Zura Bio Limited, a clinical-stage company specializing in immunology, recently presented promising data from a Phase 1 clinical study of their lead candidate, tibulizumab (ZB-106), at the Annual European Congress of Rheumatology (EULAR) 2024 in Vienna. This study focused on evaluating tibulizumab for the treatment of Sjogren’s syndrome, while preclinical data have also shown potential for rheumatoid arthritis (RA).

Tibulizumab is a humanized bispecific dual antagonist antibody combining the properties of two existing antibodies: TALTZ® (ixekizumab) and tabalumab. It is designed to neutralize both IL-17A and BAFF, two targets implicated in autoimmune and inflammatory diseases.

In the Phase 1 study, tibulizumab demonstrated excellent tolerance and effective neutralization of IL-17A and BAFF in patients with Sjogren’s syndrome. This randomized, double-blind, placebo-controlled study included 25 participants, 21 of whom received tibulizumab in varying doses over a 12-week period. The doses administered were 30 mg, 100 mg, and 300 mg at four-week intervals, with one group receiving 300 mg every two weeks. Four participants received a placebo.

The study found that tibulizumab was generally well tolerated across all doses. Serum levels of IL-17A and BAFF increased following tibulizumab administration, indicating successful target engagement. At doses of 100 mg and above, the serum concentrations appeared to plateau, suggesting near-maximum engagement of the targets.

Additionally, total B cell counts were dose-dependently reduced in participants, and the administration of tibulizumab was associated with lower levels of Th1 cells. The drug also modulated several inflammatory mediators, including serum amyloid A, interleukins 5 and 10, and basic fibroblast growth factor. These reductions indicate that tibulizumab may have potential therapeutic applications in other autoimmune conditions as well.

Preclinical data on tibulizumab’s application in rheumatoid arthritis were also presented. In a mouse model of RA, the study evaluated the effects of inhibiting IL-17A and BAFF, individually and in combination. Mice treated with the combination of anti-IL-17A and anti-BAFF antibodies showed significantly lower cumulative clinical disease scores compared to controls. This combined inhibition also resulted in less pronounced disease signs and inflammation, as well as a significant reduction in anti-collagen antibodies.

These preclinical results suggest that the dual inhibition of IL-17A and BAFF could be more effective than targeting either pathway alone. This approach shows promise for treating RA and potentially other autoimmune diseases.

Zura Bio plans to continue the clinical development of tibulizumab. The drug is expected to enter Phase 2 clinical trials for systemic sclerosis in the fourth quarter of 2024 and for hidradenitis suppurativa in the second quarter of 2025. The company also has completed Phase 1/1b studies in both Sjogren’s syndrome and rheumatoid arthritis.

Zura Bio is focused on advancing a portfolio of therapeutic indications for tibulizumab, ZB-168, and torudokimab (ZB-880). Their goal is to demonstrate the efficacy, safety, and dosing convenience of these dual-pathway antibodies in treating autoimmune and inflammatory diseases, including systemic sclerosis and other conditions with unmet medical needs.

The company’s efforts are part of a broader mission to develop innovative treatments for autoimmune and inflammatory diseases, aiming to improve patient outcomes through novel therapeutic strategies.