MSL: Thank you for meeting with me today, Dr. Williams. I'd like to discuss our biologic for severe eosinophilic asthma and some of the recent data.

Dr. Williams: I've been using several biologics for my severe asthma patients. What differentiates your IL-5 receptor antagonist from the other approved options?

MSL: Our molecule binds directly to the IL-5 receptor alpha on eosinophils rather than to IL-5 itself. This results in antibody-dependent cell-mediated cytotoxicity in addition to blocking the IL-5 pathway. In our phase 3 program, we demonstrated a 50% reduction in annual exacerbation rate compared to placebo across all comers, but a 65% reduction in patients with blood eosinophils ≥300 cells/μL.

Dr. Williams: How does that compare with the IL-5 inhibitors already on the market?

MSL: While there haven't been direct head-to-head studies, our indirect comparison analysis suggests potentially greater reductions in exacerbations in patients with higher eosinophil counts. We also see a more rapid and complete depletion of blood eosinophils, typically within 24 hours of the first dose.

Dr. Williams: I have several patients with both asthma and COPD overlap. Any data in this population?

MSL: We have a dedicated phase 3b study in asthma-COPD overlap syndrome that completed enrollment last year. Preliminary data suggest efficacy in reducing exacerbations regardless of fixed airflow obstruction. The full results will be presented at the upcoming ATS conference.

Dr. Williams: What about oral corticosteroid reduction? Many of my severe patients are steroid-dependent.

MSL: Our oral corticosteroid reduction study demonstrated a median reduction of 50% in daily OCS dose, with 56% of patients able to reduce their dose to ≤5mg per day. Importantly, 23% were able to completely eliminate OCS use while maintaining asthma control.

Dr. Williams: Those are impressive results. How durable is the response? I've seen some patients lose efficacy over time with biologics.

MSL: Our open-label extension data through 3 years show sustained reductions in exacerbation rates and improvements in lung function. The eosinophil-depleting effect is maintained with no evidence of tachyphylaxis. We have some patients now out to 5 years with continued benefit.

Dr. Williams: What about comorbidities? Many of my severe asthma patients also have chronic rhinosinusitis with nasal polyps or atopic dermatitis.

MSL: We've observed improvements in nasal polyp scores in patients with comorbid CRSwNP, with a 54% reduction in the need for nasal polyp surgery in our long-term follow-up. For atopic dermatitis, we don't see significant improvement, which is expected given the different pathophysiology. We're currently studying the combination with an IL-4/IL-13 inhibitor for patients with multiple Type 2 inflammatory conditions.

Dr. Williams: Safety is always a concern with biologics. What's been observed in the long-term studies?

MSL: The most common adverse events are injection site reactions and headache, which typically diminish over time. We haven't identified any new safety signals in patients treated for up to 5 years. Helminth infections were rare but did occur at a slightly higher rate than placebo, consistent with the eosinophil-depleting mechanism of action.

Dr. Williams: What about administration? The regimen seems similar to other biologics.

MSL: It's administered subcutaneously every 4 weeks. A unique aspect is our auto-injector device, which has an ultra-thin needle and slow injection technology that our patient satisfaction surveys show is associated with less injection pain compared to other devices. We also offer a comprehensive patient support program that includes injection training and reimbursement assistance.

Dr. Williams: That's helpful. I have several patients who might benefit from this approach. Are there any ongoing studies looking at biomarkers beyond blood eosinophils for patient selection?

MSL: Yes, we're exploring several biomarkers including periostin, FeNO, and urinary LTE4. Preliminary data suggest that a composite score incorporating multiple biomarkers may better predict super-responders than eosinophils alone. We're also investigating bronchial epithelial gene signatures through an optional bronchoscopy substudy.

Dr. Williams: Very interesting. Is there a registry or real-world evidence study I could participate in?

MSL: We have an ongoing severe asthma registry that's collecting real-world data on biologic use and outcomes. I'd be happy to connect you with our clinical operations team to discuss potential participation. The registry is designed to follow patients for up to 10 years, regardless of which therapies they receive.

Dr. Williams: I'd appreciate that information. Thank you for the scientific discussion.

MSL: Thank you for your time, Dr. Williams. I'll send over the registry information along with our recent publications on the OCS-sparing data.