Connect Biopharma (NASDAQ:CNTB) CEO Barry Quart outlined the company’s focus on rademikibart, an IL-4 receptor alpha monoclonal antibody he described as a “next-generation DUPIXENT,” during a presentation at the Leerink Partners Global Healthcare Conference. Quart emphasized both chronic and acute-care opportunities in respiratory disease, pointing to upcoming clinical catalysts and recent mechanistic findings that the company believes differentiate the drug from existing IL-4/IL-13 pathway therapies.
Positioning rademikibart as a “next-generation” IL-4Rα antibody
Quart said rademikibart has shown “excellent activity” in both atopic dermatitis and asthma. He highlighted data from a chronic asthma study where the company observed a rapid onset of effect for a biologic, including “very dramatic improvements in FEV1” in less than 24 hours.
- A “modest decline in eosinophils” observed with rademikibart, compared with a “pretty substantial increase” seen with DUPIXENT.
- In precision-cut lung slice experiments, rademikibart improved the effectiveness of beta-agonists, while DUPIXENT had “no impact” on beta-agonist effect.
Quart also discussed what he called a longer “functional half-life,” tying it to receptor internalization and prolonged pharmacologic effect even when drug levels fall. In atopic dermatitis, he cited results showing “excellent efficacy at Q4 weeks,” and said that in a dosing comparison similar to a DUPIXENT study design, Connect’s Q4-week data looked “identical” to Q2-week dosing, whereas the prior DUPIXENT experience showed a significant drop-off at Q4 weeks.
Moving into acute exacerbations in asthma and COPD
Quart said the rapid onset observed in chronic asthma created an opportunity to pursue acute exacerbations—an area he characterized as largely unchanged for decades, where standard treatment remains bronchodilators and prednisone. He argued that despite stabilizing patients short-term, outcomes are often poor, with roughly half of patients seeking additional medical care within four weeks.
Connect has initiated two Phase II studies—one in asthma and one in COPD—enrolling patients experiencing acute exacerbations. Patients receive standard of care and are then randomized to rademikibart or placebo, with endpoints focused on “the rate and the time to treatment failure” over four weeks post-treatment. Quart said top-line results are expected mid-year.
IV administration study aims to accelerate onset for emergency departments
To potentially speed onset further, Connect is evaluating intravenous administration. Quart said the company is running a small IV study in stable asthma and COPD patients to see if improvements can occur earlier than with subcutaneous dosing. He said data from the IV study are expected late in the current quarter.
Quart provided additional details on the IV program, noting that an initial phase in healthy volunteers established pharmacokinetics and tolerability, including the ability to administer as a “two-minute IV push” that was “very well tolerated.” He said the company is now looking for earlier FEV1 improvement in patients, acknowledging variability in FEV1 measurements. Quart referenced clinical relevance thresholds from the literature, stating that in COPD, improvements over about 100 mL can be clinically meaningful, and he said the company would like to see benefits similar to the prior chronic study, where improvements were approximately 250 mL to 350 mL across arms, but achieved more quickly.
Quart also said having both IV and subcutaneous presentations could enable different pricing strategies: IV use in the emergency department setting and a subcutaneous autoinjector for chronic administration. He argued that differential presentations could help meet pricing constraints in hospitals while preserving flexibility in outpatient markets.
Trial design, enrollment approach, and rationale for the “white space”
Quart described acute exacerbation treatment as a competitive “white space,” stating there are no other drugs in development for acute treatment and that currently approved biologics for asthma and COPD carry labeling that warns not to use them for acute exacerbations. He said about 1 million asthma patients and about 1.3 million COPD patients visit U.S. emergency departments annually, with similar numbers in Europe, adding that urgent care and clinic visits expand the total addressable population.
Asked why other biologics have not been developed for acute use, Quart cited expectations that anti-inflammatory effects take days to weeks. He pointed to a prior study of benralizumab (the ABRA study), where separation in treatment failure curves emerged after three weeks but not earlier, contrasting that with rademikibart’s rapid onset in earlier asthma work.
On Seabreeze trial design, Quart said Connect is using treatment failure as the primary endpoint, similar to ABRA. He cited ABRA’s reported treatment failure rate of about 45% within four weeks and said Connect is using 45% as the assumed standard-of-care failure rate. Quart said the studies are powered at about 85% to detect a 50% reduction in treatment failure and will also collect additional data including FEV1, symptoms, and hospitalization duration for health economic analyses.
Quart acknowledged enrollment challenges in emergency settings and said Connect is using a dual enrollment strategy: enrolling directly from emergency departments and also “pre-enrolling” high-risk patients identified by pulmonologists and allergists, who provide consent and baseline data in a calmer environment. He said the time from pre-enrollment to exacerbation has been “less than two months” so far and added that additional sites were expected to come online soon. Quart also said the company is running studies in both Northern and Southern Hemispheres to capture peak seasons for asthma and COPD.
Market access work and China partnership update
Quart said early payer work suggested a “small band” of acceptable pricing for a hospital-based biologic, citing approximately $600 to $700 per dose. He contrasted that with DUPIXENT’s monthly wholesale acquisition cost, which he stated as $3,800, and said a lower price point is important for adoption in ER and hospital settings.
He also discussed market research indicating that an acute indication could serve as a pathway to chronic use: Quart said clinicians showed significantly greater interest in chronic prescribing when a drug is known to work quickly, and that after acute administration, clinicians wanted to keep patients on the same drug chronically “75% of the time.”
On the company’s China partnership with Simcere, Quart said Simcere has a one-year atopic dermatitis dataset scheduled for a late-breaking oral presentation at the American Academy of Dermatology meeting later in the month, and that a New Drug Application is pending in China. He said Connect anticipates a potential approval in the second half of the year, which would trigger milestones. Quart said $110 million in milestones remain under the agreement across regulatory, development, and commercial events, and that Connect is entitled to tiered royalties starting in the high single digits and reaching low double digits. He added that Simcere has a large chronic asthma study ongoing that should complete early next year.
Quart also noted evolving FDA openness to a single Phase III trial in some cases, and said the company believes Phase III studies conducted in China could serve as supportive data for additional development in Western markets.
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.
