By Fineline Cube HBM Holdings Limited (HKG: 2142) announced that Windward Bio AG, the company’s partner, has reported positive interim results from the Phase 2 portion of the POLARIS‑1 clinical trial of HBM9378/WIN378, a fully human ultra‑long‑acting monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), in asthma — and that the Phase 3 portion of POLARIS‑1 has been initiated.
Trial Milestone
| Item | Detail |
|---|---|
| Trial | POLARIS‑1 (NCT07120503) — global Phase 2/3 study in adults with uncontrolled asthma |
| Conducted By | Windward Bio AG (development partner of HBM Holdings) |
| Milestone 1 | Positive interim analysis from the Phase 2 portion (147 patients enrolled) |
| Milestone 2 | Phase 3 portion initiated |
| Originator | HBM Holdings Limited (HKG: 2142) |
| Announcement Date | 8 Sep 2026 |
| Next Steps | Phase 3 execution (trial design, dosing interval, endpoints, enrollment targets, and readout timing not disclosed) |
Drug Profile & Mechanism of Action
- Molecule: HBM9378/WIN378 — a novel fully human, ultra‑long‑acting monoclonal antibody with a unique binding mode to inhibit TSLP. The dual nomenclature reflects the originator/partner structure between HBM Holdings and Windward Bio.
- Target Biology: TSLP (thymic stromal lymphopoietin) is an epithelial‑derived alarmin cytokine released in response to allergens, viruses, and pollutants; because it acts at the apex of the inflammatory cascade — upstream of both type 2 (eosinophilic) and non‑type 2 pathways — its blockade can benefit a broader asthma population than phenotype‑restricted interleukin‑targeted biologics.
- Innovation: The only known investigational drug that blocks TSLP signaling by binding to two different sites on TSLP, interfering with the binding of TSLP to both of its co‑receptors on the cell surface of epithelial cells.
- Engineering: Designed for improved potency, extended half‑life, and silenced effector function — Fc modifications intended to sustain target suppression over long dosing intervals, consistent with the durable Week 24 responses observed after a single dose.
Clinical Evidence – POLARIS‑1 Phase 2 Interim Analysis
| Endpoint | Result (Single Dose, Week 24) | Placebo‑Adjusted | Statistical Significance |
|---|---|---|---|
| FEV1 (forced expiratory volume in one second) | Dose‑dependent mean increases of up to 174 mL | Up to +256 mL | p=0.033 |
| FeNO (fractional exhaled nitric oxide) | Dose‑dependent mean reductions of up to 24 ppb (−43 %) | – | p=0.006 |
| Blood EOS (eosinophil count) | Mean reductions of up to 200 cells/µL (−51 %) | – | p<0.0001 |
| Safety | Well tolerated with favorable safety results | – | Detailed AE profile not disclosed |
The interim analysis evaluated responses at Week 24 following a single dose of HBM9378/WIN378 in the 147‑patient Phase 2 cohort of the global POLARIS‑1 study (NCT07120503) in adults with uncontrolled asthma. All three disclosed endpoints — lung function (FEV1), type 2 airway inflammation (FeNO), and systemic type 2 inflammation (blood eosinophils) — moved favorably and dose‑dependently, forming the data package that supported initiation of the Phase 3 portion.
Market Impact & Outlook
- Competitive Positioning: The results position HBM9378/WIN378 against tezepelumab, the only approved TSLP‑blocking antibody, in a biologic asthma market otherwise crowded with IL‑5 and IL‑4Rα agents. TSLP’s upstream mechanism keeps the addressable population broader than phenotype‑restricted competitors.
- Dosing Differentiation: The dual‑site binding and ultra‑long‑acting pharmacokinetics — evidenced by sustained Week 24 responses after a single dose — translate into a potential infrequent‑dosing regimen, a commercially meaningful advantage in a chronic indication where injection burden drives adherence and payer preference.
- Licensing Model Validation: For HBM Holdings (HKG: 2142), the data validate its platform‑driven out‑licensing model: the company originated the asset while Windward Bio runs global development, with HBM positioned to benefit from milestones and deal economics — terms not disclosed.
- Program‑Defining Advance: Initiation of the Phase 3 portion commits Windward Bio to the registration path, signaling confidence that the interim package cleared the pre‑specified bar for advancement.
- Franchise Expansion Potential: As a market observation, TSLP’s upstream alarmin biology keeps the class expandable into adjacent indications — such as COPD and chronic rhinosinusitis — should asthma Phase 3 succeed; no such plans were disclosed.
- Key Metrics to Watch: Full Phase 2 data presentation at upcoming respiratory congresses, Phase 3 design disclosure including dosing interval and exacerbation‑rate endpoints, and any milestone payments triggered for HBM Holdings.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical development timelines, Phase 3 execution, and therapeutic expectations for HBM9378/WIN378. Actual results may differ due to risks including confirmatory Phase 3 outcomes, long‑interval dosing safety profiles, competitive shifts in the biologic asthma landscape, and the terms of the HBM–Windward collaboration.-Fineline Info & Tech