Connect Biopharma (NASDAQ:CNTB) shared new clinical and preclinical updates on rademikibart, its IL-4 receptor alpha monoclonal antibody, highlighting preliminary top-line results from an intravenous (IV) clinical pharmacology study in asthma and COPD and presenting phase III atopic dermatitis data from a late-breaker session at the American Academy of Dermatology meeting.
Company frames rademikibart as differentiated within the IL-4Rα class
Barry Quart, Chief Executive Officer and Director, said the company believes rademikibart is “highly differentiated” from other drugs targeting IL-4 receptor alpha, citing a faster onset of effect, larger lung function improvements in asthma patients, the potential for less frequent dosing, and a different eosinophil profile versus dupilumab.
Quart also said the company has “consistently” observed low conjunctivitis rates with rademikibart that were not differentiated from placebo, which he positioned as a potential advantage given conjunctivitis rates cited for dupilumab.
Preclinical airway findings point to potential beta-agonist interaction
Quart reviewed preclinical work in human airway smooth muscle cells and human precision-cut lung slice models exploring airway relaxation biology. He said rademikibart increased phosphorylated HSP20, which he described as a marker of airway smooth muscle relaxation, and that this effect differed from what was observed with dupilumab.
In lung slice experiments, Quart said rademikibart improved bronchodilation and shifted the formoterol dose-response curve back toward baseline in the presence of inflammatory cytokines, while dupilumab showed no effect in that model. He said a second lab reproduced the observation in a larger set of samples. In Q&A, Quart characterized the potentiation of beta agonists as an “off-target effect,” adding that the “exact molecular basis” remains unclear, though the company believes the phenomenon is real and differentiated from dupilumab and potentially other biologics used in asthma and COPD.
Preliminary IV study results show rapid FEV1 improvements in asthma and COPD
Quart said Connect’s current development emphasis is on treating acute exacerbations of asthma and COPD, describing the acute setting as a “complete white space” because existing biologics and newer therapies are approved for chronic management and have warnings not to be used for acute exacerbations or bronchospasm.
He presented preliminary top-line results from an IV clinical pharmacology study, including a healthy volunteer component (Part A) and a patient component (Part B). In Part A, Quart said a 2-minute IV push was “very well tolerated” with similar pharmacokinetics to slower infusion, allowing the company to use that approach in patients.
In Part B, Connect evaluated stable asthma and COPD patients to assess whether IV dosing could accelerate improvement in lung function. Quart emphasized that it was a small study (12 patients total, with 10 active and 2 placebo) and that bronchodilators were withheld for the first day to better isolate rademikibart’s effect.
- Asthma: Quart said placebo-corrected FEV1 improvement was observed as early as 15 minutes, with variability in early timepoints. By 3–4 hours, he said the improvement stabilized in the 200–250 mL range and reached the 200–300 mL range by the end of the first day, with effects maintained through 29 days of follow-up.
- COPD: Quart said the COPD cohort showed “very robust” FEV1 improvement within 15–30 minutes and that the improvement was generally maintained in the 300–400 mL range, despite variability typical of spirometry in COPD patients.
Quart said the rapid onset supports the view that a “second mechanism” may contribute to rademikibart’s airway effects beyond IL-4Rα blockade, pointing back to the preclinical HSP20 and bronchodilation findings as potential clues.
He also compared the COPD signals to other therapies, citing smaller placebo-corrected changes reported for other approaches and noting that, in this small study, rademikibart produced larger improvements. Quart said the IV approach could also support emergency department use with a lower dose due to subcutaneous bioavailability of “about 50%,” and he said the company may evaluate lower IV doses going forward.
On safety, Quart said there were “none to speak of” in the small IV study.
Mid-year readouts expected from acute exacerbation phase II trials
Quart said Connect has two acute exacerbation phase II studies ongoing in asthma and COPD, with top-line results anticipated “mid-year.” The trials use standard of care (prednisone and a beta-agonist bronchodilator) and then randomize patients to rademikibart or placebo, with the primary goal of reducing “treatment failure,” which he described as returning for additional medical care—including another course of prednisone—during the 28-day endpoint window.
Quart said the company used data suggesting roughly 45% of patients return for medical care within four weeks following an exacerbation, referencing the investigator-initiated ABRA study from the U.K. He said Connect is targeting a 50% reduction in treatment failure.
In Q&A, Quart said the company is planning to switch to IV dosing as it moves toward phase III for acute treatment, while evaluating whether additional bridging work is needed between the small IV study and larger trials. He also attributed early variability in asthma spirometry to test variability and the small sample size, stating he would not “read too much into an individual data point.”
Partner-led phase III atopic dermatitis data highlights 52-week efficacy and low conjunctivitis rates
Quart also reviewed phase III atopic dermatitis data from RADIANT-AD, a study sponsored by Simcere Pharmaceutical, Connect’s partner in Greater China. Quart said Connect is eligible for milestones and tiered royalties from Simcere and, during Q&A, confirmed there is “$110 million” in remaining milestones tied to development, regulatory, and commercial endpoints, though the company has not disclosed individual milestone amounts. He said the first approval milestone would be expected to be tied to atopic dermatitis, with another milestone potentially tied to an asthma approval in China following Simcere’s ongoing chronic asthma study.
On RADIANT-AD, Quart described response rates at 16 weeks and particularly at 52 weeks as “quite impressive,” citing:
- IGA: 87.1% responders at 52 weeks
- EASI-75: 96.6% response rate at 52 weeks
- EASI-90: high response rates (Quart did not provide a specific percentage on the call)
- Pruritus: substantial improvement
He said conjunctivitis rates during the placebo-controlled phase were not differentiated from placebo and remained “substantially lower” than other products over longer-term follow-up. Quart also reiterated that prior Connect-sponsored atopic dermatitis data suggested efficacy could be maintained with every-four-week dosing (Q4W) after an induction period, with high maintenance of response through 52 weeks.
Looking ahead, Quart said the most significant upcoming catalyst is the mid-year readout from the two phase II acute exacerbation studies. He also said there is a pending new drug application in China for atopic dermatitis, with potential approval timing “between midyear and end of year.” Quart added that Connect reported $55 million in cash equivalents and short-term investments at the end of the third quarter, plus proceeds from a financing announced that morning, and said the company expects its cash to fund operations into the second half of 2027.
About Connect Biopharma (NASDAQ:CNTB)
Connect Biopharma Holdings Ltd. is a clinical-stage biopharmaceutical company focused on the discovery and development of monoclonal antibody therapies for immune-mediated disorders. Headquartered in Singapore with a research and commercial presence in the United States, the company applies proprietary technology platforms to target novel pathways in inflammatory and autoimmune diseases.
The company’s lead product candidate, CBP-201, is a fully human monoclonal antibody that antagonizes the interleukin-31 receptor, a key mediator of chronic pruritus in conditions such as atopic dermatitis and prurigo nodularis.
