REG - AstraZeneca PLC - Tozorakimab met OBERON/TITANIA primary endpoints

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RNS Number : 4266Y  AstraZeneca PLC  27 March 2026

This announcement contains inside information

 

27 March 2026

 

Tozorakimab met primary endpoint in both OBERON and TITANIA Phase III trials
in patients with COPD

 

First-ever IL-33-targeting biologic to demonstrate statistically significant
and highly clinically meaningful reductions in COPD exacerbations in two
replicate Phase III clinical trials

 

Positive high-level results from the Phase III OBERON and TITANIA trials in
patients with chronic obstructive pulmonary disease (COPD) showed that
tozorakimab reduced the annualised rate of moderate-to-severe COPD
exacerbations compared with placebo, in the primary population of former
smokers, and in the overall population, which included former and current
smokers, and patients across all blood eosinophil* counts and all stages of
lung function severity. Tozorakimab was generally well tolerated with a
favourable safety profile.

 

Tozorakimab is a potential first-in-class monoclonal antibody targeting
interleukin-33 (IL-33), that uniquely inhibits the signalling of the reduced
and oxidised forms of IL-33, offering the potential to both reduce
inflammation and disrupt the cycle of mucus dysfunction that contribute to
COPD worsening.(1-4) In the OBERON and TITANIA trials, tozorakimab was studied
in patients with COPD still experiencing exacerbations while on inhaled
standard of care.(5,6) Patients received tozorakimab 300mg or placebo on top
of standard of care once every four weeks.

Nearly 400 million people are diagnosed with COPD, a heterogenous and
progressive disease and the 3(rd) leading cause of death globally.(7,8) Even
when on inhaled standard of care, more than 50% of patients experience
exacerbations, putting them at an increased risk of cardiopulmonary events and
mortality.(9-12)

 

Frank Sciurba, MD, FCCP, Professor of Pulmonary and Critical Care Medicine,
University of Pittsburgh, Chief Investigator of LUNA programme, said: "These
trial results suggest that targeting the IL-33 pathway with tozorakimab
delivers meaningful clinical benefit in a trial representing a broad COPD
population, independent of smoking status and eosinophilic levels. COPD has
long been a difficult-to-treat disease with inherent heterogeneity and
significant unmet need, with up to half of patients worldwide at risk of
exacerbations, hospitalisations, cardiopulmonary events, and death -
underscoring the importance of these results for advancing COPD science."

 

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "Today's tozorakimab results deliver the first two
confirmatory Phase III trials for an IL-33 biologic, which is a major
scientific advancement in COPD, the world's third leading cause of death.
Tozorakimab works in a fundamentally different way from other biologics,
inhibiting the signalling of the reduced and oxidised forms of IL-33 to both
decrease inflammation and disrupt the cycle of mucus dysfunction that are key
disease drivers in COPD."

 

The full results from the OBERON and TITANIA clinical trials will be shared
with the scientific community at an upcoming medical meeting.

 

Additional Phase III trials of tozorakimab in COPD, PROSPERO and MIRANDA, are
ongoing.(13,14) Tozorakimab is also being studied in a Phase III trial for
severe viral lower respiratory tract disease and in a Phase II trial in
asthma.(15,16)

 

*eosinophil: a type of white blood cell, which at increased levels may
contribute to inflammation in respiratory diseases.(17)

 

Notes

 

COPD

COPD, the third leading cause of death (excluding COVID-19) worldwide, is a
progressive respiratory condition characterised by persistent airflow
limitation and chronic inflammation of the airways.(8,18) Common symptoms
include breathlessness, chronic cough and excess mucus production.(18) 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.(18) These COPD exacerbations have a profound impact on the
lives of those with the disease, accelerating disease progression, increasing
hospitalisations, and increasing the risk of future cardiopulmonary events -
including heart attacks, all of which can be life-threatening.(12,18) In the
US, exacerbations cause more than 2,500 emergency department visits per
day.(19) Only 50% of COPD patients live more than 3.5 years after their first
severe exacerbation.(20)

 

Phase III LUNA programme

Tozorakimab's Phase III COPD development programme includes four clinical
trials: OBERON, TITANIA, PROSPERO and MIRANDA.

 

OBERON and TITANIA

OBERON and TITANIA are 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 enrolment. A total of 2,306 patients
were randomised in both trials irrespective of blood eosinophil count or
smoking status and across all stages of lung function severity.(5,6) 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 enrolment, patients received standard-of-care inhaled maintenance
therapy for at least three months. The primary endpoint is annualised rate of
moderate-to-severe COPD exacerbations in former smokers with COPD.  A key
secondary endpoint measured the annualised rate of moderate-to-severe COPD
exacerbations in the overall population of former and current smokers.(5,6)

 

PROSPERO

The PROSPERO trial is a randomised, long-term extension clinical trial that
enrolled patients who completed the OBERON or TITANIA trials. The primary
endpoint is the annualised rate of severe COPD exacerbations in former smokers
with COPD over 104 weeks. A total of 1,713 patients were randomised in this
trial.(13) Results are expected in H1 2026.

 

MIRANDA

MIRANDA is a Phase III double-blind, placebo-controlled trial 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 enrolment. A total of 1,454 patients were randomised in this trial,
recruited irrespective of blood eosinophil count or smoking status and across
all stages of lung function severity.(14) Patients were placed on a regimen of
tozorakimab 300mg once every two weeks, or placebo over the course of 52 weeks
on top of inhaled therapy.

 

Prior to enrolment, patients received standard-of-care inhaled maintenance
therapy for at least three months. The primary endpoint is annualised rate of
moderate-to-severe COPD exacerbations in former smokers with COPD. Key
secondary endpoints include the annualised rate of moderate-to-severe COPD
exacerbations in the overall population of former and current smokers.(14)
Results are expected in H1 2026.

 

Tozorakimab

Tozorakimab is being developed by AstraZeneca as a first-in-class potent human
immunoglobulin monoclonal antibody that binds to interleukin (IL-33).
Tozorakimab targets the top of the inflammatory cascade uniquely inhibiting
IL-33 signalling in two ways, thereby suppressing inflammation and disrupting
the cycle of mucus dysfunction.(1) Tozorakimab is currently being investigated
in Phase III clinical trials for COPD and severe viral lower respiratory tract
disease and a Phase II trial for asthma.(5,6,13-16) 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.(21)

 

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 (https://www.astrazeneca.com/)

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, 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 (http://www.astrazeneca.com/) and follow the
Company on Social Media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

Contacts

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.

 

References

1.   England E, Rees DG, Scott IC, et al. Tozorakimab (MEDI3506): an
anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to
reduce inflammation and epithelial dysfunction. Sci
Rep. 2023;13:9825.    

2.   Singh D, Guller P, Reid F, et al. A Phase 2a trial of the IL-33 mAb
tozorakimab in patients with COPD: FRONTIER-4. Eur Respir J 2025;doi
10.1183/13993003.02231-2024.

3.   Strickson S, Houslay KF, Negri VA, et al. Oxidised IL-33 drives COPD
epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex. Eur
Respir J 2023;62:2202210.

4.   Strickson S, et al. Distinct Pharmacological Profiles of IL-33
Antibodies. [Poster Presentation]. Presented at the American Thoracic Society
(ATS) 2024. May 2024.

5.   Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in
Symptomatic Chronic Obstructive Pulmonary Disease With a History of
Exacerbations (OBERON).  Online . Available at:
https://clinicaltrials.gov/study/NCT05166889. Accessed March 2026.   

6.   Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in
Symptomatic Chronic Obstructive Pulmonary Disease With a History of
Exacerbations. (TITANIA).  Online . Available at:
https://clinicaltrials.gov/study/NCT05158387. Accessed March 2026.

7.   Montes de Oca M, Perez-Padilla R, Celli B, et al. The global burden of
COPD: epidemiology and effect of prevention strategies. Global Epidemiology of
Chronic Respiratory Disease. 2025; 13(18):709-724.

8.   World Health Organization (WHO). The top 10 causes of death. 2024.
Available from:
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
Accessed March 2026.

9.   Chen S, Small M, Lindner L, Xu X. Symptomatic burden of COPD for
patients receiving dual or triple therapy. Int J Chron Obstruct Pulmon Dis
2018;13:1365-1376. 

10.  Chen S, Miravitlles M, Rhee CK, et al. Patients with chronic
obstructive pulmonary disease and evidence of eosinophilic inflammation
experience exacerbations despite receiving maximal inhaled maintenance
therapy. Int J Chron Obstruct Pulmon Dis 2022;17:2187-2200. 

11.  Nordon C, Carstens D, Fageras M, et al. Exacerbation and mortality
in COPD patients on triple inhaler and at high exacerbation
risk. Eur Respir J 2024;64(Suppl. 68):PA1287 (Abstract). 

12.  Singh D, Han MK, Hawkins NM, et al. Implications of cardiopulmonary risk
for the management of COPD: a narrative review. Adv
Ther. 2024;41:2151-2167. 

13.  Clinicaltrials.gov. Long-term Efficacy and Safety of Tozorakimab in
Participants With Chronic Obstructive Pulmonary Disease With a
History of Exacerbations (PROSPERO).  Online . Available at:
https://clinicaltrials.gov/study/NCT05742802. Accessed March 2026.

14.  Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in
Symptomatic Chronic Obstructive Pulmonary Disease With a History of
Exacerbations (MIRANDA).  Online . Available at:
https://clinicaltrials.gov/study/NCT06040086. Accessed March 2026.

15.  Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Patients
Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (TILIA).
 Online . Available at: https://clinicaltrials.gov/study/NCT05624450 Accessed
March 2026.

16.  Clinicaltrials.gov Dose Range Finding Study to Assess Efficacy and
Safety of Tozorakimab in Adults With Uncontrolled Asthma on Medium-to-High
Dose Inhaled Corticosteroids (UMBRIEL).  Online . Available at:
https://clinicaltrials.gov/study/NCT06932263 Accessed March 2026.

17.  Jackson D, Akuthota P, Roufosse F, Eosinophils and eosinophilic immune
dysfunction in health and disease. Eur Respir Rev 2022 31(163):210150.

18.  GOLD. Global Strategy for the Diagnosis, Management, and Prevention of
Chronic Obstructive Pulmonary Disease: 2026 Report. Available from:
https://goldcopd.org/2026-gold-report-and-pocket-guide/ Accessed March 2026.

19.  American Lung Association. COPD Trends Brief: Burden. Available from:
https://www.lung.org/research/trends-in-lung-disease/copd-trends-brief/copd-burden
Accessed March 2026.

20.  Suissa S, Dell'Aniello S, Ernst P. Long-term natural history of chronic
obstructive pulmonary disease: severe exacerbations and mortality. Thorax
2012;67:957-963.

21.  AstraZeneca. Clinical Trials Appendix Q3 2025 Results Update. Available
from:
https://www.astrazeneca.com/content/dam/az/PDF/2025/9m-q3/9M-and-Q3-2025-results-clinical-trials-appendix.pdf
Accessed March 2026.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

This announcement contains information that AstraZeneca PLC is obliged to make
public pursuant to the EU Market Abuse Regulation (596/2014) and the
assimilated EU Market Abuse Regulation (596/2014) as it forms part of the law
of the United Kingdom by operation of the European Union (Withdrawal) Act
2018. This announcement was submitted for publication, through the agency of
the contact person(s) set out above, at 7:00 GMT on 27 March 2026.

 

 

 

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