Tilrekimig – BiotechReality – Information Intelligence System for Biopharma

NEW YORK – Pfizer Inc. (NYSE: PFE) has reported positive topline results from its Phase 2 clinical trial of tilrekimig atopic dermatitis phase 2 data, marking a significant milestone for the investigational trispecific antibody (PF-07275315). The study successfully met its primary efficacy endpoint, demonstrating that the treatment significantly improved skin clearance in adults suffering from moderate to severe atopic dermatitis compared to a placebo. Breakthrough Efficacy in Skin Clearance (EASI-75) The Phase 2 study focused on the percentage of participants achieving EASI-75 a standard industry metric representing at least a 75% reduction in the Eczema Area and Severity Index at Week 16. Tilrekimig, which is administered once monthly, showed competitive and dose-dependent efficacy across the tested groups. In Stage 2 of the trial, the placebo-adjusted results for achieving EASI-75 were: Low Dose: 38.7% Middle Dose: 51.9% High Dose: 49.4% The data suggests that the two highest dose levels may offer meaningful improvements over current standard-of-care biologics. By simultaneously targeting three key pathways interleukin-4 (IL-4), interleukin-13 (IL-13), and thymic stromal lymphopoietin (TSLP) tilrekimig aims to provide a more comprehensive approach to treating Type 2 (Th2) immune-mediated inflammation. Primary Efficacy Data (EASI-75 at Week 16) The primary endpoint of the study was the percentage of patients achieving EASI-75 (a 75% or greater reduction from baseline in the Eczema Area and Severity Index) at Week 16. The trial utilized a placebo-controlled, dose-ranging design. Placebo-Adjusted EASI-75 Success Rates: Low Dose: 38.7% (statistically significant vs. placebo) Middle Dose: 51.9% (statistically significant vs. placebo) High Dose: 49.4% (statistically significant vs. placebo) Key Finding: The middle and high doses demonstrated efficacy levels that Pfizer describes as "potentially meaningful improvements" over currently approved standard-of-care biologics (such as IL-4Rα inhibitors like dupilumab). Trial Design & Methodology The Phase 2 study was a randomized, double-blind, placebo-controlled trial conducted in four overlapping stages to evaluate two different trispecific antibodies: Stage 1 (Proof of Concept): Tested a high dose of tilrekimig vs. placebo and a high dose of ompekimig (PF-07264660, targeting IL-4, IL-13, and IL-33) vs. placebo. Both met their primary endpoints. Stage 2 (Dose-Ranging): Evaluated three monthly dosing regimens of tilrekimig to determine the optimal dose for Phase 3. Stage 3 (Prior Biologic Users): Specifically testing tilrekimig in patients who have previously failed or transitioned from other biologic treatments (Ongoing). Stage 4 (Ompekimig Dose-Ranging): Evaluating dose-ranging for the second trispecific candidate, ompekimig (Ongoing). Mechanism of Action (The "Trispecific" Advantage) Tilrekimig is a first-in-class trispecific antibody. Its data is significant because it simultaneously inhibits three distinct pro-inflammatory pathways involved in Type 2 (Th2) inflammation: IL-4 (Interleukin-4): Drives Th2 cell differentiation. IL-13 (Interleukin-13): A central mediator in skin barrier disruption and itch. TSLP (Thymic Stromal Lymphopoietin): An "upstream" cytokine that triggers the initial inflammatory cascade. By blocking TSLP in addition to IL-4/13, the data suggest a more comprehensive suppression of the "itch-scratch" cycle than targeting IL-4/13 alone. Safety and Tolerability Data The safety profile of tilrekimig was a critical component of the Phase 2 readout, as multi-target antibodies can sometimes increase the risk of side effects. General Safety: Tilrekimig was well-tolerated with no dose-dependent safety signals. Adverse Events (AEs): Rates were comparable to the placebo group. Common AEs: Infections, skin/subcutaneous tissue disorders, and administration site reactions. Serious Adverse Events (SAEs): Three SAEs were reported during the study; however, all three were adjudicated as unrelated to the study treatment. Ocular Safety (Conjunctivitis): Notably, the frequency of conjunctivitis (eye inflammation) was lower than the rates typically reported for existing IL-4 receptor alpha inhibitors. This is a significant clinical differentiator for patients who struggle with eye-related side effects on current biologics. Clinical Implications & Pipeline Expansion Based on this data, Pfizer is moving tilrekimig into a pivotal Phase 3 study for Atopic Dermatitis later in 2026. The trial data also support its expansion into other Th2-mediated diseases: Asthma: Currently in Phase 2. COPD (Chronic Obstructive Pulmonary Disease): Phase 2b/3 study recently initiated. A Potential First-in-Class Trispecific Antibody Unlike traditional monoclonal antibodies that target a single receptor, tilrekimig is a trispecific antibody. This "three-in-one" mechanism is designed to inhibit multiple drivers of inflammation without impacting healthy cell receptors. We are encouraged by the topline Phase 2 results for tilrekimig, Combining the potent inhibition of IL-4/13 and TSLP pathways has the potential to deliver improved efficacy over the current standard of care for atopic dermatitis. Mike Vincent, Pfizer’s Chief Inflammation & Immunology Officer Pfizer Last Modified:

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Pfizer Announces Positive Phase 2 Results for Trispecific Antibody Tilrekimig in Moderate to Severe Atopic Dermatitis

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