Zura Bio's TibuSURE Study: A New Hope for Systemic Sclerosis Patients

Zura Bio, a clinical-stage, multi-asset immunology company, has launched the global Phase 2 TibuSURE study to evaluate tibulizumab, a novel dual-pathway antibody, in adults with systemic sclerosis (SSc). This study marks a significant step forward in the quest for more effective treatments for this life-threatening autoimmune disease.

Systemic sclerosis, also known as scleroderma, is a rare and potentially fatal autoimmune disease characterized by tissue inflammation and fibrosis. It primarily affects the skin and lungs but can also impact the heart, liver, kidneys, digestive tract, and vascular system. The most common symptoms include skin thickening, extreme sensitivity to cold in the extremities, muscle numbness and swelling, joint stiffness and reduced mobility, fibrosis in the lungs and heart, kidney dysfunction, and gastrointestinal issues. Despite its severity, there is a high unmet medical need due to the limited treatment options available for individuals living with SSc.

Tibulizumab, an investigational humanized, tetravalent bispecific dual-antagonist antibody, is a fusion of Taltz® (ixekizumab) and tabalumab, engineered to bind to and neutralize both IL-17A and BAFF. This dual-pathway approach offers a novel strategy for managing SSc by concurrently targeting two pivotal pathways involved in inflammation and fibrosis. By addressing the multi-organ pathology of SSc, tibulizumab holds the potential to provide deeper efficacy and greater benefits for patients compared to current treatments.

The planned Phase 2 clinical trial, a double-blind, randomized (1:1), placebo-controlled study, is designed to evaluate the safety, tolerability, and efficacy of tibulizumab in approximately 80 participants with early diffuse cutaneous systemic sclerosis (dcSSc). The anticipated study aims to demonstrate improvements in skin and lung symptoms, two primary complications of SSc, and includes an open-label extension. The trial is expected to initiate in Q4 2024, with an Orphan Drug Designation request already submitted to the FDA in the same quarter.

Tibulizumab's convenient Q4W subcutaneous dosing schedule can significantly enhance patient adherence and treatment satisfaction. This dosing regimen allows for less frequent administration compared to monthly or weekly injections, reducing the burden on patients. A study in rheumatoid arthritis patients showed that a Q4W dosing schedule for an anti-IL-17A antibody improved adherence and reduced the risk of treatment discontinuation (Ann Rheum Dis, 2019). Additionally, a Q4W dosing schedule for an anti-BAFF antibody in systemic lupus erythematosus patients was associated with higher treatment satisfaction and better quality of life (Arthritis Rheumatol, 2018).



Tibulizumab's dual-pathway approach offers a potential advantage over single-pathway inhibitors in treating SSc. By simultaneously targeting IL-17A and BAFF, tibulizumab can address both inflammatory and fibrotic processes, which are key drivers of SSc. This mechanism holds the potential to provide deeper efficacy and greater benefits for patients affected by this life-threatening autoimmune disease. In contrast, single-pathway inhibition has demonstrated modest effects in rheumatic diseases like SSc.



The TibuSURE study aims to evaluate tibulizumab's safety, tolerability, and efficacy in approximately 80 participants with early diffuse cutaneous systemic sclerosis (dcSSc), with primary endpoint being the modified Rodnan Skin Score (mRSS). Key efficacy endpoints include lung disease assessment, physical function measurement, and the revised Combined Response Index in Systemic Sclerosis (rCRISS). If successful, tibulizumab could become a best-in-class treatment for SSc, addressing certain urgent, unmet needs of this patient population.

In conclusion, Zura Bio's TibuSURE study represents a significant step forward in the quest for more effective treatments for systemic sclerosis. Tibulizumab's dual-pathway mechanism offers a novel approach to managing this life-threatening autoimmune disease, with the potential to provide deeper efficacy and greater benefits for patients. The convenient Q4W subcutaneous dosing schedule can enhance patient adherence and treatment satisfaction, further improving the lives of those affected by SSc. As the study progresses, the medical community eagerly awaits the results, hoping that tibulizumab will pave the way for a new era of SSc treatment.