Zura Bio Limited (Nasdaq: ZURA) has commenced its Phase 2 TibuSURE study, a global trial evaluating tibulizumab for the treatment of systemic sclerosis (SSc) in adults. This trial represents a significant advancement in the therapeutic landscape for SSc, a rare and life-threatening autoimmune disease affecting approximately 300,000 individuals worldwide, including around 100,000 in the United States.
The TibuSURE study is a double-blind, placebo-controlled trial designed to assess the safety, tolerability, and efficacy of tibulizumab in approximately 80 participants with early diffuse cutaneous systemic sclerosis (dcSSc). The study includes a 24-week efficacy period followed by a 28-week open-label extension (OLE).
The primary endpoint of the trial is the modified Rodnan Skin Score (mRSS), a measure of skin thickening. Key secondary endpoints include assessments of lung disease using quantitative high-resolution computed tomography (qHRCT) and forced vital capacity (FVC), physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the revised Combined Response Index in Systemic Sclerosis (rCRISS).
Rationale for Dual-Pathway Inhibition
Tibulizumab is an investigational humanized, tetravalent bispecific dual-antagonist antibody. It is engineered to bind to and neutralize both IL-17A and BAFF, two pivotal pathways involved in the inflammation and fibrosis characteristic of SSc. This dual-targeting mechanism offers a novel strategy compared to existing treatments that typically focus on single-pathway inhibition.
"Single-pathway inhibition has demonstrated modest effects in rheumatic diseases like SSc. This is why we believe tibulizumab's dual-pathway approach holds the potential to be best-in-class, aiming to provide deeper efficacy and greater benefits for patients affected by this life-threatening autoimmune disease," said Kiran Nistala, MBBS, PhD, Chief Medical Officer and Head of Development at Zura Bio.
Christopher Denton, PhD, FRCP, FMedSci, Professor of Experimental Rheumatology at the University College London and Consultant Rheumatologist and Head of the Centre for Rheumatology at the Royal Free Hospital, London, added, "Systemic sclerosis is a heterogeneous and complex autoimmune disease characterized by both inflammatory and fibrotic processes, for which effective therapies remain limited. Tibulizumab’s dual-targeting mechanism offers a novel strategy by concurrently targeting two pivotal pathways involved in inflammation and fibrosis. This mechanism holds the potential to address the multi-organ pathology of SSc and help improve the lives of patients with SSc."
Systemic Sclerosis: Unmet Needs and Current Therapies
Systemic sclerosis is characterized by chronic inflammation and progressive fibrosis of connective tissues, primarily affecting the skin and lungs, but also potentially impacting the heart, liver, kidneys, digestive tract, and vascular system. Symptoms include skin thickening and extreme sensitivity to cold in the extremities. Currently, only two disease-modifying therapies are FDA-approved for severe lung complications of SSc (SSc-ILD), highlighting the significant unmet medical need for treatments that address the disease across multiple organ systems.
Tibulizumab: A Potential Best-in-Class Therapy
Tibulizumab is a fusion of Taltz® (ixekizumab) and tabalumab. Prior to being in-licensed by Zura Bio, Phase 1/1b studies of tibulizumab were conducted in Sjögren’s syndrome and rheumatoid arthritis. Zura Bio anticipates initiating a Phase 2 clinical trial for tibulizumab in the treatment of hidradenitis suppurativa in Q2 2025. Tibulizumab is currently an investigational compound and is not approved for marketing by the FDA or any other regulatory authority.
With a strong financial position, including a cash balance of $89.8 million as of the first quarter of 2024, Zura Bio is well-positioned to advance its clinical development programs. Analysts maintain a positive outlook on Zura Bio, with price targets ranging from $5 to $26, reflecting confidence in the company's ongoing research and its ability to meet milestones in the development of its therapeutic candidates.
