Connect Biopharma's rademikibart advances Phase II trials

Connect Biopharma (Nasdaq: CNTB) reported that an independent Data Monitoring Committee has reviewed interim efficacy data from its Phase II Seabreeze STAT studies of rademikibart in acute asthma and COPD exacerbations, recommending no change to sample size and identifying no safety concerns — a procedural checkpoint that keeps the program on track for mid-2026 topline readouts.

The Seabreeze STAT Asthma and Seabreeze STAT COPD trials are randomized, double-blind, placebo-controlled Phase II studies evaluating rademikibart as add-on treatment in adults experiencing acute exacerbations of asthma or COPD with type 2 inflammation.

The DMC's interim review was triggered after a minimum of 50 patients in each study had completed at least 28 days of follow-up. The committee examined three pre-specified measures: treatment failure at 28 days, rate of new exacerbations through 28 days, and change from baseline in FEV1. No numerical efficacy results were disclosed. On safety, the company said there have been no treatment-related serious or severe adverse events and no discontinuations due to adverse events in either study.

The absence of a sample-size adjustment is a procedural signal rather than an efficacy readout. DMCs typically recommend increases when interim data suggest the study is underpowered to detect a treatment effect, and reductions — or early stopping — when a benefit or harm threshold has been crossed. A recommendation to continue unchanged indicates the trial remains within its pre-specified operating assumptions, though it provides no information about the direction or magnitude of the treatment effect. Topline data remain the relevant evidentiary milestone.

Rademikibart targets the interleukin-4 receptor alpha subunit, blocking both IL-4 and IL-13 signaling and thereby suppressing the Th2 inflammatory pathway implicated in type 2 airway disease. The mechanism is shared with dupilumab, the Sanofi and Regeneron anti-IL-4Rα antibody that generated Phase III COPD data in 2024 through the BOREAS and NOTUS trials. Those programs evaluated dupilumab as a maintenance therapy in patients with type 2 COPD, a distinct clinical context from the acute exacerbation add-on design Connect is pursuing. Cross-trial comparisons are limited by differences in patient population, dosing schedule, endpoints, and treatment setting.

The acute exacerbation niche is mechanistically unoccupied by approved biologics. Current standard of care in acute asthma and COPD exacerbations centers on short-acting bronchodilators, systemic corticosteroids, and, in severe cases, intravenous magnesium sulfate. AstraZeneca's Airsupra, a fixed-dose combination of albuterol and budesonide approved by the FDA in January 2023, introduced an anti-inflammatory rescue option but operates through inhaled corticosteroid rather than cytokine blockade. No biologic targeting the IL-4/IL-13 axis has been approved or previously studied in the acute exacerbation setting, which is the clinical rationale underlying the Seabreeze STAT program design.

Whether that rationale translates into measurable benefit depends on whether rademikibart can act rapidly enough in an acute context to influence the endpoints the DMC reviewed. Biologics targeting cytokine receptors typically require days to weeks to exert meaningful anti-inflammatory effects, and the 28-day treatment failure endpoint in the Seabreeze STAT studies reflects that time horizon. Connect has cited preclinical and early clinical data suggesting a faster onset of FEV1 improvement than might be expected from the class, though that claim awaits Phase II confirmation.

Connect said it plans to meet with the FDA to align on a Phase III program following the mid-2026 topline readouts from both Seabreeze STAT studies.

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