Zura Bio Advances Dual-Target Bispecific Tibulizumab Through Phase 2 Trials in Autoimmune Diseases
核心洞察
Zura Bio is advancing tibulizumab, a bispecific antibody targeting IL-17A and BAFF (搜索), through two Phase 2 trials for autoimmune inflammatory disorders.
The company expects Phase 2 data from hidradenitis suppurativa (搜索) trials in Q4 2024, with 225 patients enrolled and primary endpoint measuring abscess and nodule count reduction.
A second Phase 2 trial in systemic sclerosis (搜索) is planned for first half 2027, focusing on patients with diffuse subtype and using modified Rodnan skin score as primary endpoint.
Zura Bio outlined its clinical strategy at Guggenheim Securities' Emerging Outlook Biotech Summit 2026, highlighting upcoming Phase 2 readouts for tibulizumab, its lead bispecific antibody targeting autoimmune and inflammatory diseases. The company expects two key data readouts over the next 12-18 months as it transitions "from being an execution company to being a data company," according to newly appointed CEO Sandeep Kulkarni.
Dual-Target Bispecific Approach
Tibulizumab represents a novel therapeutic approach, simultaneously targeting IL-17A and BAFF (搜索) (B-cell activating factor). Kulkarni described these two immune targets as "orthogonal," suggesting the dual mechanism may be particularly suited for complex autoimmune disorders that cannot be easily categorized as primarily T-cell mediated or B-cell mediated.
The bispecific was licensed from Eli Lilly in 2023 and engineered using sequences from tabalumab, a BAFF (搜索)-targeting program Lilly advanced into Phase 3, grafted with complementarity-determining regions from ixekizumab, which is approved as Taltz across multiple indications. Lilly designed tibulizumab to have drug-like properties including low immunogenicity and a naturally long half-life.
Phase 1 Safety and Dosing Profile
Lilly previously tested tibulizumab in 78 subjects across three Phase 1 programs, including healthy volunteers and cohorts in rheumatoid arthritis (搜索) and Sjögren's syndrome (搜索). Chief Medical Officer Kiran Nistala reported that in Lilly's multidose study, only one participant developed a treatment-emergent anti-drug antibody, representing under 5% of participants, which he characterized as "low...for bispecifics."
The molecule was designed so both binding arms have high potency with relatively similar affinity, supporting equivalent target engagement for BAFF (搜索) and IL-17. For Phase 2 dosing, the steady-state regimen is once every four weeks, with an initial loading period using three doses in the first four weeks. The top dose of 300 mg every four weeks is predicted to provide at least 98% target engagement for both arms.
Hidradenitis Suppurativa Trial
Zura's first key readout will come in Q4 2024 from its Phase 2 trial in hidradenitis suppurativa (搜索) (HS), a chronic inflammatory dermatologic condition with complex and heterogeneous biology. The company expanded the HS study size to 225 patients and selected a dermatology-focused contract research organization, limiting investigators to those with HS experience.
While IL-17 inhibition has clinical validation in HS, the company emphasized evidence supporting a B-cell/BAFF (搜索) component, citing translational observations including B-cells detected in HS lesions and elevated BAFF in affected areas. They also referenced recent clinical data from Novartis' platform study that included ianalumab (a BAFF pathway modulator), remibrutinib (a BTK (搜索) inhibitor), and iscalimab (a CD40 (搜索)-targeting agent), with all three agents targeting the "B-cell axis" showing clinical efficacy.
The trial allows up to 30% TNF inhibitor failures but otherwise focuses on biologic-naïve patients and excludes IL-17 failures. The primary endpoint is reduction in abscess and nodule count, with the trial powered for HiSCR 75, assuming a 20%-25% delta versus placebo. The company views this range as broadly appropriate for clinically meaningful benefit.
Systemic Sclerosis Program
Zura's second Phase 2 program targets systemic sclerosis (搜索) (SSc), with data expected in the first half of 2027. Kulkarni said the company chose SSc due to high unmet need and the lack of approved therapies for the disease as a whole, describing it as associated with high morbidity and mortality.
The trial focuses on patients with the diffuse subtype, selected for sufficiently severe skin disease to detect signal. Approximately two-thirds of enrolled patients are expected to have interstitial lung disease (搜索). The primary endpoint is modified Rodnan skin score (mRSS), with the study powered around a three-to-four unit mRSS delta, referencing a minimal clinically important difference of about four units.
The 24-week study duration is designed to observe skin changes, while the company will use more sensitive methods for lung assessment, including AI-based quantification of high-resolution CT scans. Standard of care is allowed, with mycophenolate mofetil being most typical, requiring patients to be on a stable dose for at least four months.
Pipeline and Strategic Focus
Beyond tibulizumab, Zura has two additional assets: crebankitug (an IL-7 receptor (搜索) antibody acquired from Pfizer) and torudokimab (an IL-33 (搜索) program acquired from Lilly). However, Kulkarni emphasized that the company's primary focus is executing the tibulizumab clinical plan, describing Zura as "ruthless" in capital allocation. The company indicated it would provide more details later this year on potential additional indications beyond HS and SSc.