New data at CHEST 2026 provide further evidence supporting the favorable clinical profile of tozorakimab in COPD

Key analyses from the positive Phase III OBERON and TITANIA trials and results from the PROSPERO long-term extension trial reinforce tozorakimab's broad and durable benefits in patients with chronic obstructive pulmonary disease (COPD).^1,2,3 These benefits were seen in a broad population of patients including former and current smokers, and patients across all blood eosinophil counts (BEC) and all stages of lung function severity.^1,2,3 The findings are being presented as three late-breaking presentations at The American College of Chest Physicians (CHEST) 2026 Annual Meeting.

New analysis of key secondary endpoint in OBERON and TITANIA: Evaluating Respiratory Symptoms in COPD (E-RS:COPD)

A new analysis of OBERON and TITANIA demonstrates that tozorakimab 300mg, administered once every four weeks, led to rapid reduction in daily symptoms from the first dose with nominally significant benefits sustained throughout the treatment period to week 52, compared to placebo; the reductions were seen in patients recruited irrespective of blood eosinophil counts.¹ These results were measured by the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) tool, which evaluates common daily respiratory symptoms across three domains: breathlessness, chest symptoms (chest discomfort, tightness, or pain) and cough/mucus-related symptoms (cough frequency, severity and sputum production).¹ See Table 1.

Phase III long-term extension trial: PROSPERO

Findings from the PROSPERO long-term extension trial of the OBERON and TITANIA trials will also be presented at CHEST. PROSPERO had a different primary endpoint than the OBERON and TITANIA trials: the annualized rate of severe COPD exacerbations (those leading to hospitalizations and death) in the primary population of former smokers up to 104 weeks.² While the results from the primary endpoint in former smokers showed a numerical, but not statistically significant reduction in severe exacerbations (21%; 0.26 vs 0.33 annualized rates; RR 0.79 [95% CI 0.61,1.01] p=0.0587) there was a nominally significant reduction in severe exacerbations in the overall population of former and current smokers (27%; 0.26 vs 0.36 annualized rates; RR 0.73 [95% CI 0.58, 0.91] p=0.0046).² Consistent with the primary endpoint of the OBERON and TITANIA pivotal trials, PROSPERO results showed continued tozorakimab treatment maintained the reduction in moderate and severe COPD exacerbations in former smokers (32%; 1.37 vs 2.02 annualized rates; RR 0.68 [95% CI 0.59, 0.78] p<0.0001) and the overall population (30%; 1.43 vs 2.05 annualized rates; RR 0.70 [95% CI 0.62, 0.79] p<0.0001) a secondary endpoint in PROSPERO.^2,4 See Table 2. The safety and tolerability profile of tozorakimab through 104 weeks in PROSPERO was consistent with the profile observed in the OBERON and TITANIA trials.^2,4

Exploratory analysis on mucus plugging from PROSPERO

The data further reinforce tozorakimab as the first biologic to reduce mucus plugging in a broad population of patients with COPD.³ Mucus plug score is an important emerging outcome measure, as mucus plugs have been associated with worse outcomes in COPD.⁵ The LUNA program performed the largest-to-date evaluation in a COPD development program of computed tomography (CT) imaging scans assessing mucus plugs in the lungs, and the analysis showed that tozorakimab reduced the mean segmental mucus plug score by 28% from baseline at week 52, with this reduction maintained through week 80, compared with a 17% increase from baseline with placebo at week 80.³ See Table 3.

The full results from the OBERON and TITANIA trials were published in the New England Journal of Medicine.

Henrik Watz, MD, LUNA program Investigator, Principal Investigator at Velocity Clinical Research in Ahrensburg and Professor of Clinical Research in Respiratory Medicine at Luebeck University, Germany said: "Tozorakimab has an important impact on breathlessness, cough, and chest symptoms in a broad population of patients in addition to its significant and sustained reduction in moderate and severe COPD exacerbations, with a favorable safety profile. Based on the totality of the data, I believe tozorakimab has the potential to be a groundbreaking step forward in the treatment of COPD."

Caterina Brindicci, Senior Vice President & Global Head Research and Development, Respiratory, AstraZeneca, said: "These results reinforce tozorakimab's unique approach of inhibiting the signaling of two forms of IL-33 which translates to real clinical impact delivering durable and consistent benefits across a broad population. With these data, we further our understanding of the underlying drivers of COPD and how tozorakimab has the potential to help address how we treat this complex disease in a fundamentally new way."

Tozorakimab is a potential first-in-class monoclonal antibody targeting interleukin-33 (IL-33) that uniquely inhibits the signaling of the reduced and oxidized forms of IL-33, offering the potential to both reduce inflammation and disrupt the cycle of mucus dysfunction that contribute to COPD worsening.^6-10

The Biologics License Application for tozorakimab 300mg, administered once every four weeks, has been accepted for Priority Review by the US Food and Drug Administration as an add-on maintenance treatment for adult patients with COPD. The Prescription Drug User Fee Act date is anticipated during the first quarter of 2027 following use of a Priority Review voucher. Tozorakimab is currently under regulatory review for the treatment of COPD in major markets, including the EU, Japan and China. It is also being studied in a Phase II trial in severe asthma and a Phase III trial in severe viral lower respiratory tract disease.^11,12

Table 1: Tozorakimab treatment was shown to improve daily respiratory symptoms in patients with COPD: new analysis from the OBERON and TITANIA studies (Abstract: 2989224)¹

*Confidence intervals are not adjusted for multiplicity.

Table 2: Long-term efficacy of tozorakimab in COPD: an integrated analysis of OBERON, TITANIA and the PROSPERO extension study (Abstract: 2989298)²

# Rate of severe exacerbations in former smokers was the primary endpoint of PROSPERO. P-values for subsequent endpoints should be interpreted in terms of nominal significance only.

*Note: Reduction in the annualized rate of moderate and severe exacerbations was the primary endpoint of the OBERON and TITANIA Phase III trials.

Table 3: In an exploratory analysis, tozorakimab leads to long-term reductions in the number of lung segments with mucus plugs in patients with COPD: results from the Phase III PROSPERO extension study (Abstract: 2989378)³

* P-values are not adjusted for multiplicity and should be interpreted in terms of nominal significance only.

Notes

COPD
COPD, the third leading cause of death (excluding COVID-19) worldwide, is a progressive respiratory condition characterized by persistent airflow limitation and chronic inflammation of the airways.^13,14 Common symptoms include breathlessness, chronic cough and excess mucus production.¹⁴ These symptoms can worsen over time and contribute to ongoing inflammation and bronchoconstriction, making it difficult to breathe and increasing the risk of COPD exacerbations.¹⁴ These COPD exacerbations have a profound impact on the lives of those with the disease, accelerating disease progression, increasing hospitalizations, and increasing the risk of future cardiopulmonary events - including heart attacks, all of which can be life-threatening.^14,15 In the US, exacerbations cause more than 2,500 emergency department visits per day.¹⁶ Only 50% of COPD patients live more than 3.5 years after their first severe exacerbation.¹⁷

OBERON and TITANIA
OBERON and TITANIA were replicate Phase III double-blind, placebo-controlled trials investigating the efficacy and safety of tozorakimab in adults with symptomatic COPD with a history of ≥2 moderate or ≥1 severe COPD exacerbations in the 12 months prior to enrollment. A total of 2,306 patients were randomized in both trials, including former and current smokers, and patients across all blood eosinophil counts and all stages of lung function severity.^18,19 Patients were placed on a regimen of tozorakimab 300mg once every four weeks, or placebo over the course of 52 weeks on top of inhaled therapy.

Prior to enrollment, patients received standard-of-care inhaled maintenance therapy for at least three months. The primary endpoint was annualized rate of moderate-to-severe COPD exacerbations in former smokers with COPD. A key secondary endpoint measured the annualized rate of moderate-to-severe COPD exacerbations in the overall population of former and current smokers.^18,19

AstraZeneca announced positive high-level results from these trials in March and announced the positive full results in September.^20,21

PROSPERO
The PROSPERO trial was a randomized, long-term extension clinical trial that enrolled patients who completed the OBERON or TITANIA trials. PROSPERO had a different primary endpoint, which is the annualized rate of severe COPD exacerbations (hospitalizations and death) in former smokers with COPD over 104 weeks. A total of 1,713 patients were randomized in this trial.²²

Tozorakimab

Tozorakimab is being developed by AstraZeneca as a first-in-class potent human immunoglobulin monoclonal antibody that binds to interleukin-33 (IL-33). Tozorakimab targets the top of the inflammatory cascade uniquely inhibiting IL-33 signaling in two ways, thereby suppressing inflammation and disrupting the cycle of mucus dysfunction.^6-10 Tozorakimab is currently being investigated in a Phase III clinical trial for severe viral lower respiratory tract disease and a Phase II trial for asthma.^11,12 Tozorakimab was granted Fast Track Designation by the US Food and Drug Administration for the treatment of severe viral lower respiratory tract disease in November 2023 and for COPD in December 2024.²³

AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

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Reference

1. Sciurba FC, Bhatt SP, Watz H, et al. Tozorakimab treatment improves daily respiratory symptoms in patients with chronic obstructive pulmonary disease: results from the OBERON and TITANIA studies. [Abstract: 2989224]. Presented at: The American College of Chest Physicians (CHEST) 2026 Annual Meeting; October 18-21, 2026; Phoenix, Arizona.

2. Watz H, Sciurba FC, Bourdin A, et al. Long-term efficacy and safety of tozorakimab in patients with COPD: an integrated analysis of OBERON, TITANIA and the PROSPERO extension study. [Abstract: 2989298]. Presented at: The American College of Chest Physicians (CHEST) 2026 Annual Meeting; October 18-21, 2026; Phoenix, Arizona.

3. Washko G, Sciurba FC, Watz H, et al. Tozorakimab leads to long-term reductions in the number of lung segments with mucus plugs in patients with COPD: results from the Phase III PROSPERO extension study [Abstract: 2989378]. Presented at: The American College of Chest Physicians (CHEST) 2026 Annual Meeting; October 18-21, 2026; Phoenix, Arizona.

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