New data for TEZSPIRE and BREZTRI demonstrate AstraZeneca’s innovation and commitment to transform care in COPD

AstraZeneca will showcase new clinical and real-world data across its leading inhaled, biologic and early science respiratory portfolio at the American Thoracic Society (ATS) International Conference, in San Diego, CA from May 17 - 22, 2024. The company will present 59 abstracts, including 12 late-breaking posters, with a focus on unmet needs in chronic obstructive pulmonary disease (COPD), severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA), as well as other chronic respiratory diseases.

Sharon Barr, Ph.D., Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: “Data at ATS demonstrate our progress in advancing a new wave of innovative treatments, moving beyond symptom control into disease modification, remission and one day, cure. Today, COPD patients have highly limited options if their disease is uncontrolled on inhaled medicines. We’re encouraged by the results of the COURSE Phase IIa data exploring tezepelumab in a broad population of COPD patients beyond those with baseline blood eosinophils above 300 cells/μL and look forward to these data being presented at the ATS International Conference.”

Ruud Dobber, Ph.D, Executive Vice President and President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Our broad pipeline and portfolio of inhaled and biologic medicines are the cornerstone of our bold ambition to transform respiratory care. COPD remains one of the leading causes of death globally, and at ATS we will present important real-world evidence reinforcing the need to address cardiopulmonary risk in COPD as well as the potential for our inhaled triple therapy BREZTRI to reduce this risk.”

Highlights of AstraZeneca data at ATS 2024 include:

Leading transformation in COPD care by investigating novel biologic medicines, targeting key drivers across a broad range of patients including: TEZSPIRE^® (tezepelumab) beyond severe asthma targeting thymic stromal lymphopoietin (TSLP) and tozorakimab, to reduce excess inflammation and epithelial remodelling in IL-33 driven disease

• COURSE Phase IIa trial: late-breaking data from a proof-of-concept trial investigating tezepelumab in moderate to very severe COPD patients. Importantly this trial included COPD patients irrespective of inflammatory drivers, baseline blood eosinophil levels, emphysema, chronic bronchitis, and smoking status.¹
• New mechanistic data from tozorakimab investigating its ability to inhibit IL-33ox biologic effects and block the RAGE-EGFR pathway vs. other IL-33 antibodies.²

Investigating the effect of inhaled triple therapy, BREZTRI^® (budesonide/ glycopyrrolate/ formoterol fumarate, BGF), on cardiopulmonary outcomes and deepening insights into the connection between COPD and cardiopulmonary risk

• ETHOS Phase III trial post-hoc analysis of cardiopulmonary outcomes: the new analysis explores the effect of BGF across a range of cardiopulmonary outcomes beyond traditional COPD endpoints.³
• SKOPOS-MAZI retrospective analysis: the study will provide new real-world evidence comparing mortality rates in patients who start therapy with BGF single inhaler triple therapy (SITT), versus multiple inhaler triple therapy (MITT) [open combination triple therapies (ICS/LABA+ LAMA or LABA/LAMA + ICS)] among patients with COPD in the US.⁴
• EXACOS-CV multi-country retrospective cohort study: late-breaking real-world data across 8 countries, from over 1 million patients with COPD explores the risk of serious cardiovascular events or death following a COPD exacerbation. These data add to the growing body of evidence demonstrating the importance of proactively addressing cardiopulmonary risk in COPD patients.⁵

In asthma, advancing the science in asthma rescue with AIRSUPRA^® (albuterol-budesonide), a first-in-class anti-inflammatory rescue therapy for asthma in the US⁶

• MANDALA Phase III post-hoc analysis: new efficacy data for as-needed AIRSUPRA by baseline blood eosinophil count in patients with moderate-to-severe asthma.⁷
• ACADIA trial design: outlining innovative approaches to study design for the ACADIA study of AIRSUPRA in adolescents.⁸

Early pipeline science exploring innovative modalities including novel inhaled medicines for moderate-severe add-on treatment (“pre-biologics”) to reach a broader population of patients

• Two potential first-in-class pre-biologic medicines being explored in asthma:
  • New Phase I safety and efficacy data for AZD8630/AMG 104, an inhaled TSLP inhibitor in patients with moderate-to-severe asthma.⁹
  • Findings from a preclinical study of AZD4604, an inhaled, small molecule selective JAK1 inhibitor in development for the treatment of moderate-to-severe asthma. The data explores JAK selectivity and implications for clinical inhibition compared to other currently marketed JAK inhibitors.¹⁰

Additional AstraZeneca presentations of note include results from the MANDARA Phase III trial for patients with EGPA. A highlight of the MANDARA data is the impact of FASENRA^® (benralizumab) to reduce or completely eliminate oral glucocorticoid use in these patients.¹¹

Key AstraZeneca presentations during ATS 2024:

INDICATIONS AND LIMITATIONS OF USE / ISI

AIRSUPRA^® (albuterol and budesonide)

• Contraindications: Hypersensitivity to albuterol, budesonide, or to any of the excipients
• Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a marker of destabilization of asthma and requires evaluation of the patient and their treatment regimen
• Paradoxical Bronchospasm: AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. Discontinue AIRSUPRA immediately and institute alternative therapy if paradoxical bronchospasm occurs. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister
• Cardiovascular Effects: AIRSUPRA, like other drugs containing beta₂-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, and/or other symptoms. If such effects occur, AIRSUPRA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. Therefore, AIRSUPRA, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
• Do Not Exceed Recommended Dose: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
• Hypersensitivity Reactions, Including Anaphylaxis: Can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA, as demonstrated by cases of anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria. Discontinue AIRSUPRA if such reactions occur
• Risk of Sympathomimetic Amines with Certain Coexisting Conditions: AIRSUPRA, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines
• Hypokalemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients. The decrease in serum potassium is usually transient, not requiring supplementation
• Immunosuppression and Risk of Infections: Due to possible immunosuppression from the use of inhaled corticosteroids (ICS), potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
• Oropharyngeal Candidiasis: Has occurred in patients treated with ICS agents. Monitor patients periodically. Advise patients to rinse his/her mouth with water, if available, without swallowing after inhalation
• Hypercorticism and Adrenal Suppression: May occur with very high doses in susceptible individuals. If such changes occur, consider appropriate therapy
• Reduction in Bone Mineral Density: Decreases in bone mineral density have been observed with long-term administration of ICS. For patients at high risk for decreased bone mineral density, assess initially and periodically thereafter
• Glaucoma and Cataracts: Have been reported following the long-term administration of ICS, including budesonide, a component of AIRSUPRA
• Effects on Growth: Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population
• Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, and dysphonia
• Drug Interactions: AIRSUPRA should be administered with caution to patients being treated with:
  • Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
  • Short-acting bronchodilators (concomitant use of additional beta-agonists with AIRSUPRA should be used judiciously to prevent beta-agonist overdose)
  • Beta-blockers (may block pulmonary effects of beta-agonists and produce severe bronchospasm)
  • Diuretics or non-potassium-sparing diuretics (may potentiate hypokalemia or ECG changes). Consider monitoring potassium levels
  • Digoxin (may decrease serum digoxin levels). Consider monitoring digoxin levels
  • Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants (Use AIRSUPRA with extreme caution; may potentiate effect of albuterol on the cardiovascular system)
• Use AIRSUPRA with caution in patients with hepatic impairment, as budesonide systemic exposure may increase. Monitor patients with hepatic disease

INDICATION

AIRSUPRA is a combination of albuterol, a beta2-adrenergic agonist and budesonide, a corticosteroid, indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older.

Please see full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products.

BREZTRI AEROSPHERE^® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol

• BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients
• BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with use of LABA in patients with COPD
• BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition
• BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist
• BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
• Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation
• Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap
• Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
• Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI
• Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy
• Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur
• If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy
• Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy
• Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles
• Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content
• Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur
• Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur
• Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines
• Be alert to hypokalemia or hyperglycemia
• Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%)
• BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system
• BREZTRI should be administered with caution to patients being treated with:
  • Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
  • Adrenergic drugs (may potentiate effects of formoterol fumarate)
  • Xanthine derivatives, steroids, or non-potassium sparing diuretics (may potentiate hypokalemia and/or ECG changes)
  • Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm)
  • Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI
• Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored

INDICATION

BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

LIMITATIONS OF USE

Not indicated for the relief of acute bronchospasm or for the treatment of asthma.

Please see full BREZTRI Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products.

FASENRA ^® (benralizumab)

CONTRAINDICATIONS

Known hypersensitivity to benralizumab or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). Discontinue in the event of a hypersensitivity reaction.

Acute Asthma Symptoms or Deteriorating Disease

FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.

Injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.

USE IN SPECIFIC POPULATIONS

A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/Fasenra.

The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATION

FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 6 years and older, and with an eosinophilic phenotype.

• FASENRA is not indicated for treatment of other eosinophilic conditions
• FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus

Please read full Prescribing Information, including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products.

TEZSPIRE^® (tezepelumab)

CONTRAINDICATIONS

Known hypersensitivity to tezepelumab-ekko or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions were observed in the clinical trials (eg, rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (ie, days). In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE.

Acute Asthma Symptoms or Deteriorating Disease

TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.

Abrupt Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves.

Live Attenuated Vaccines

The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥3%) are pharyngitis, arthralgia, and back pain.

USE IN SPECIFIC POPULATIONS

There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATION

TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.

Please see full Prescribing Information, including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products.

Notes

Data presented does not reflect any head-to-head comparisons.

Chronic Obstructive Pulmonary Disease (COPD)

COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.¹² COPD is the third leading cause of death due to chronic disease and the sixth leading cause of mortality in the United States. COPD accounts for the majority of chronic lower respiratory mortality in the US at 150,000 deaths per year, and data suggests patients with COPD are, on average, 50 times more likely to die from their condition compared to those with asthma. ^13,14

The lungs and heart are fundamentally linked and work together.¹⁵ COPD mechanisms elevate the risk of both lung and heart events, including severe or even fatal COPD exacerbations and cardiac events, known as cardiopulmonary risk.^16-19 Approximately 1 in 5 patients with COPD will die within a year of their first hospitalisation for an exacerbation, and pulmonary and cardiac events are a key driver of mortality and the most common reasons for death in patients with COPD.^16,20-22

Severe asthma

Severe asthma is an often-debilitating, potentially fatal condition affecting up to 26 million people worldwide.^23-26 Patients may be uncontrolled despite high dosages of standard of care asthma controller medicines, experiencing frequent exacerbations and significant limitations on lung function and health-related quality of life as a result.^23,25-27

Eosinophilic granulomatosis with polyangiitis (EGPA)

EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels.^28,29 It is estimated that 118,000 people throughout the world live with EGPA.³⁰

EGPA can result in damage to multiple organs, including lungs, upper airway, skin, heart, gastrointestinal tract and nerves.²⁸ The most common symptoms and signs include extreme fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath. Without treatment, the disease may be fatal.^28,31 Almost half (47%) of patients do not achieve remission with current treatments.^28,32

AIRSUPRA

AIRSUPRA (albuterol/budesonide), formerly known as PT027, is a first-in-class SABA/ICS rescue treatment for asthma in the US, to be taken as needed. It is an inhaled, fixed-dose combination rescue medication containing albuterol (also known as salbutamol), a SABA, and budesonide, a corticosteroid, and has been developed in a pMDI using AstraZeneca’s Aerosphere delivery technology.³³

The FDA approval of AIRSUPRA was based on MANDALA and DENALI Phase III trials (Approval press release). In MANDALA, AIRSUPRA significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate-to-severe asthma when used as an as-needed rescue medication in response to symptoms. For patients treated with AIRSUPRA 180 mcg/160 mcg the annualized total systemic corticosteroids dose when compared with albuterol 180 mcg was statistically significantly different, with a reduction in mean annualized dose of 40 mg per patient. In DENALI, AIRSUPRA significantly improved lung function compared to the individual components albuterol and budesonide in patients with mild to moderate asthma.

BREZTRI

BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol fumarate) is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered via the AEROSPHERE pressurised metered-dose inhaler. BREZTRI AEROSPHERE is approved to treat COPD in more than 50 countries worldwide including the US, EU, China and Japan, and is currently being studied in Phase III trials for asthma.

FASENRA

FASENRA is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).^34,35

FASENRA (benralizumab) is currently approved in more than 80 countries, including the US, EU, and Japan, and is approved for self-administration in the US, EU and other countries.^36-38 FASENRA has been prescribed to over 100,000 patients in the US.³⁹

FASENRA is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.^40-42

FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

TEZSPIRE

TEZSPIRE (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness.^44,45 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.^46-48

Amgen collaboration

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, Amgen and AstraZeneca will jointly commercialize TEZSPIRE in North America. Amgen will record product sales in the US, with AZ recording its share of US profits as Collaboration Revenue. Outside of the US, AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue.

In addition, we are also collaborating with AstraZeneca on AMG104/AZD8630, an inhaled anti-TSLP compound currently in development for asthma. In November 2021, Amgen and AstraZeneca agreed to include AMG 104 / AZD8630 in the existing collaboration agreement. The companies share both costs and income, with no inventor royalty. AstraZeneca will be the development, manufacturing and commercial lead. AstraZeneca and Amgen will jointly commercialize AMG 104 / AZD8630 in North America, and AstraZeneca will distribute the product and book sales globally, including for the US.

Respiratory & Immunology

Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

1. Singh D, Bafadhel M, Brightling C, et al. Tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD): efficacy and safety from the Phase 2a COURSE study. [Late breaking Mini Symposium Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
2. Cohen ES, Strickson S, Scott IC, et al. Distinct pharmacology profiles of IL-33 antibodies. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
3. Singh D, Martinez FJ, Hurst JR, et al. Effect of triple inhaled therapy with budesonide/glycopyrrolate/formoterol fumarate on cardiopulmonary events in chronic obstructive pulmonary disease: a post-hoc analysis of ETHOS. [Poster Discussion]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
4. Pollack M, Rapsomaniki E, Anzueto A, et al. Increased risk of mortality for COPD patients associated with initiation of treatment with multiple inhaler triple therapy initiation versus single inhaler (budesonide/glycopyrrolate/formoterol) in the United States: the MAZI study. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
5. Pollack M, Nordon C, Rhodes K, et al. Association between severe cardiovascular events and time following exacerbations of COPD: meta-analyses of EXACOS-CV observational studies from 8 countries. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
6. AstraZeneca. AIRSUPRA® (PT027) approved in the US for asthma. Available at: https://www.astrazeneca-us.com/media/press-releases/2023/airsupra-pt027-approved-in-the-us-for-asthma.html. [Last accessed: April 2024].
7. Papi A, Chipps B, Beasley R, et al. Efficacy of as-needed albuterol-budesonide by baseline blood eosinophil count in patients greater than or equal to 18 years with moderate-to-severe asthma. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
8. Bacharier LB, Bardsley S, Dunsire L, et al. A Bayesian Dynamic Borrowing Approach to Evaluate the Efficacy of Albuterol-Budesonide As Needed in Adolescents with Asthma: Design of the ACADIA Study. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
9. Doffman S, Dosanjh D, Sadiq MW. Phase 1 safety and efficacy of AZD8630/AMG 104 inhaled anti-TSLP in healthy volunteers and patients with asthma on medium-high dose inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) with elevated baseline fractional exhaled nitric oxide (FeNO). [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
10. Riff C, Larsson J, Nilsson M, et al. Inhaled AZD4604: local Janus Kinase 1 inhibition without systemic activity. [Thematic Poster Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
11. Nair P, Wechsler M, Bourdin A, et al. Effect of benralizumab versus mepolizumab on reduction in oral glucocorticoid use in patients with eosinophilic granulomatosis with polyangiitis: Phase 3 MANDARA study. [RAPiD Poster Discussion Session]. Presented at the American Thoracic Society International Conference 2024 (17-22 May).
12. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2023. [Online]. Available at: http://goldcopd.org. [Last accessed: April 2024].
13. Centers for Disease Control and Prevention (CDC). Leading Causes of Death. United States: CDC; January 17, 2024, https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed April 11, 2024.
14. National Heart, Lung, and Blood Institute (NIH). Learn More Breathe Better: United States: NIH. https://www.nhlbi.nih.gov/BreatheBetter. Accessed April 11, 2024.
15. American Lung Association. Your Heart and Lungs: The Ultimate Relationship (2023) Available at: https://www.lung.org/blog/heart-lung-relationship. [Last accessed: April 2024].
16. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866.
17. Donaldson GC et al. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010;137:1091-1097;9-2029.
18. Watz H et al. Spirometric changes during exacerbations of COPD: A post hoc analysis of the WISDOM trial. Respir Res. 2018;19(1):251.
19. Suissa S et al. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963.
20. Lindenauer PK, Dharmarajan K, Qin L, et al. Risk Trajectories of Readmission and Death in the First Year After Hospitalization for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1009-1017.
21. García-Sanz MT, Cánive-Gómez JC, Senín-Rial L, et al. One-year and long-term mortality in patients hospitalized for chronic obstructive pulmonary disease. J Thorac Dis. 2017; 9 (3): 636‐645. doi:10.21037/jtd.2017.03.34.
22. Mannino DM et al. Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med. 2006;100: pp.115-122.
23. Chung, KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73.
24. The Global Asthma Network. The Global Asthma Report 2022. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2022.pdf. [Last accessed: April 2024].
25. Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-60.
26. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40: 364-372.
27. Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006;100(7):1139-51.
28. American Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/. [Last accessed: April 2024].
29. Furuta S, Iwamoto T, Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436.
30. AstraZeneca Data on file. 2022. REF-167820.
31. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543.
32. Cottin V, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Eur Respir J. 2016;48:1429-1441.
33. Airsupra (albuterol/budesonide) US prescribing information; 2022.
34. Kolbeck R, et al. MEDI-563, a humanized anti-IL-5 receptor a mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125:1344-1353.e2.
35. Pham TH, et al. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29.
36. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html. [Last accessed: April 2024].
37. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html. [Last accessed: April 2024].
38. AstraZeneca Annual Report 2023. Available at: https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2023/pdf/AstraZeneca_AR_2023.pdf. [Last accessed: April 2024].
39. AstraZeneca plc. FY and Q4 2023 Results. Conference call and webcast for investors and analysts. Available at: https://www.astrazeneca.com/media-centre/press-releases/2024/full-year-and-q4-2023-results.html. [Last accessed April 2024].
40. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE). Available from: https://clinicaltrials.gov/ct2/show/NCT04053634. [Last accessed: April 2024].
41. Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available at: https://clinicaltrials.gov/ct2/show/NCT04157335. [Last accessed: April 2024].
42. Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). Available from: https://clinicaltrials.gov/ct2/show/NCT04191304. [Last Accessed: April 2024].
43. Airsupra (albuterol/budesonide) US prescribing information; 2022.
44. Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.
45. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
46. AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html. [Last accessed: April 2024].
47. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html. [Last accessed: April 2024].
48. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: April 2024].

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