Tibulizumab (ZB-106) was well tolerated and
neutralized IL-17A and BAFF in a Phase 1 study in patients with
Sjogren’s syndrome
Preclinical data demonstrating the potential of
dual inhibition of IL-17A and BAFF in a rheumatoid arthritis animal
model support clinical development
Zura Bio Limited (Nasdaq: ZURA) (“Zura Bio”), a clinical-stage
immunology company developing novel dual-pathway antibodies for
autoimmune and inflammatory diseases, today 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.
“Collectively, these data add to early-phase evidence
demonstrating that dual-inhibition of both IL-17A and BAFF could be
a breakthrough approach for autoimmune and inflammatory diseases in
which single-pathway inhibition is the standard of care,” stated
Robert Lisicki, Chief Executive Officer. “The results in Sjogren’s
syndrome demonstrate that tibulizumab achieved robust target
engagement, nearing maximum serum levels following single,
well-tolerated subcutaneous doses at four-week intervals. Further,
the preclinical results suggest dual-pathway inhibition may warrant
clinical exploration in RA and other autoimmune diseases, adding to
the breadth of potential we see with tibulizumab.”
Key Findings from Phase 1 Study of Tibulizumab in Sjogren’s
Syndrome
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 poster is available in the News and Events section on the
Zura Bio website and will be archived for at least 30 days
following presentation.
Key Findings from Preclinical Study of Tibulizumab in an RA
Model
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).
The study abstract, which was accepted for publication only, is
available on the EULAR website.
ABOUT TIBULIZUMAB
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.
ABOUT ZURA BIO
Zura Bio is a clinical-stage, multi-asset immunology company
developing novel dual-pathway antibodies for autoimmune and
inflammatory diseases. Currently, Zura Bio is developing three
assets which have completed Phase 1/1b studies and are Phase 2
ready. The company is developing a portfolio of therapeutic
indications for tibulizumab (ZB-106), ZB-168, and torudokimab
(ZB-880), with a goal of demonstrating their efficacy, safety, and
dosing convenience in autoimmune and inflammatory diseases,
including systemic sclerosis and other novel indications with unmet
needs.
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version on businesswire.com: https://www.businesswire.com/news/home/20240614812438/en/
Megan K. Weinshank Head of Investor Relations ir@zurabio.com
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