Connect Biopharma (CNTB) Study result summary

Study design and objectives

• Preliminary top-line results from IV clinical pharmacology studies of rademikibart in asthma, COPD, and phase III atopic dermatitis were presented at major conferences.

• The IV studies included healthy volunteers and stable asthma/COPD patients, focusing on safety, pharmacokinetics, and rapidity of FEV1 improvement, with most patients being current smokers.

• Entry criteria for asthma/COPD included a lower limit of 200 eosinophils to select for T2-mediated disease.

• The atopic dermatitis RADIANT-AD trial was a randomized, double-blind, placebo-controlled phase 3 study in China for moderate-to-severe AD, enrolling 259 patients aged ≥12 years.

• Ongoing phase II studies in acute exacerbations of asthma and COPD are designed to assess reduction in treatment failure, with top-line results expected mid-year or mid-2026.

Key findings and results

• IV rademikibart demonstrated immediate and robust FEV1 improvements, with effects seen as early as 15 minutes and maintained through 29 days in both asthma and COPD patients.

• COPD patients showed particularly strong FEV1 improvements (300–400 mL), with peak increases up to 600 mL at 3 hours and AUC 0–12h values around 400 mL.

• Atopic dermatitis results showed 87.1% IGA responders and 96.6% EASI-75 at 52 weeks, with sustained efficacy and low rates of conjunctivitis.

• Q4-week dosing in atopic dermatitis maintained high response rates, outperforming dupilumab in long-term maintenance.

• Placebo patients switched to rademikibart showed rapid improvement, approaching active group results by week 52.

Mechanistic insights and differentiation

• Rademikibart binds IL-4 receptor alpha at a different epitope than dupilumab, with tighter binding and greater receptor internalization.

• This leads to decreased eosinophils (versus increases with dupilumab) and may explain the lower rates of conjunctivitis and enhanced efficacy.

• Preclinical models showed rademikibart increases phosphorylation of HSP20, enhancing airway relaxation and potentiating beta-agonist effects, a mechanism not seen with dupilumab.

• IV rademikibart demonstrated bronchodilation effects independent of IL-4Ra blockade, suggesting a unique mechanism.