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Expanded savings programs build on company’s longstanding commitment to addressing barriers to access and affordability for patients WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca announced it will expand the savings programs for its entire US inhaled respiratory portfolio, helping eligible patients pay no more than $35 per month for their medicine.* Expanding the savings programs will help make its inhalers more affordable to the most vulnerable patients living with asthma and chronic obstructive pulmonary disease (COPD), including those who are uninsured and underinsured. Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “AstraZeneca’s expanded savings programs build on our longstanding commitment to addressing barriers to access and affordability for patients living with respiratory diseases to ultimately help patients lead healthier lives. We remain dedicated to addressing the need for affordability of our medicines, but the system is complex and we cannot do it alone. It is critical that Congress bring together key stakeholders to help reform the healthcare system so patients can afford the medicines they need, not just today, but for the future.” Starting June 1, 2024, eligible patients will pay no more than $35 per month for all AstraZeneca US inhaled respiratory medicines, including: AIRSUPRA® (albuterol and budesonide) BEVESPI AEROSPHERE® (glycopyrrolate and formoterol fumarate) Inhalation Aerosol BREZTRI AEROSPHERE® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol SYMBICORT® (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol In addition, AstraZeneca substantially reduced the list price of SYMBICORT on January 1, 2024. The Company will continue to provide discounts and rebates off the list price to help patients afford its inhaled respiratory medicines. For more than 50 years, AstraZeneca has served respiratory patients by investing in the research and development of new drug-device combinations, as well as next-generation biologics and novel mechanisms to address the vast unmet needs of these chronic, often debilitating diseases. AstraZeneca remains dedicated to transforming patient outcomes, while ensuring access and affordability of our innovative medicines. *Terms and conditions apply. Government restrictions exclude people enrolled in federal government insurance programs from co-pay support. IMPORTANT SAFETY INFORMATION 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 Please see full Prescribing Information, including Patient Information. You may report side effects related to AstraZeneca products. BEVESPI AEROSPHERE® (glycopyrrolate and formoterol fumarate) Inhalation Aerosol CONTRAINDICATIONS All long-acting beta2-adrenergic agonists (LABAs), including formoterol fumarate, are contraindicated in patients with asthma without use of an inhaled corticosteroid. BEVESPI is not indicated for the treatment of asthma. BEVESPI is contraindicated in patients with hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of the product. WARNINGS AND PRECAUTIONS The safety and efficacy of BEVESPI AEROSPHERE in patients with asthma have not been established. BEVESPI AEROSPHERE is not indicated for the treatment of asthma Use of LABAs as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When LABAs are 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 to ICS alone. Available data do not suggest an increased risk of death with use of LABAs in patients with chronic obstructive pulmonary disease (COPD) BEVESPI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition BEVESPI should not be used for the relief of acute symptoms (ie, as rescue therapy for the treatment of acute episodes of bronchospasm). Acute symptoms should be treated with an inhaled short-acting beta2-agonist (SABA) BEVESPI should not be used more often or at higher doses than recommended, or with other LABAs, as an overdose may result If paradoxical bronchospasm occurs, discontinue BEVESPI immediately and institute alternative therapy If immediate hypersensitivity reactions occur, in particular, angioedema, urticaria, or skin rash, discontinue BEVESPI at once and consider alternative treatment BEVESPI can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, blood pressure, or symptoms. If such effects occur, BEVESPI may need to be discontinued Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines Be alert to hypokalemia and hyperglycemia Worsening of narrow-angle glaucoma or urinary retention may occur. Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction, and instruct patients to contact a physician immediately if symptoms occur ADVERSE REACTIONS The most common adverse reactions with BEVESPI (≥2% and more common than placebo) were cough, 4.0% (2.7%) and urinary tract infection, 2.6% (2.3%). DRUG INTERACTIONS Use caution if administering additional adrenergic drugs because the sympathetic effects of formoterol may be potentiated Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of formoterol Use with caution in patients taking non-potassium-sparing diuretics, as the ECG changes and/or hypokalemia may worsen with concomitant beta2-agonists The action of adrenergic agonists on the cardiovascular system may be potentiated by monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval. Therefore, BEVESPI should be used with extreme caution in patients being treated with these agents Use beta-blockers with caution as they not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in patients with COPD Avoid co-administration of BEVESPI with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects INDICATION BEVESPI AEROSPHERE is a combination of glycopyrrolate, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA), indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. LIMITATION OF USE Not indicated for the relief of acute bronchospasm or for the treatment of asthma. Please read 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. SYMBICORT® (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are 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 to ICS alone SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms SYMBICORT should not be initiated in patients during rapidly deteriorating episodes of asthma or COPD Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason Localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. Patients should rinse the mouth after inhalation of SYMBICORT Lower respiratory tract infections, including pneumonia, have been reported following the administration of ICS Due to possible immunosuppression, potential worsening of infections could occur. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur, particularly at higher doses. Particular care is needed for patients who are transferred from systemically active corticosteroids to ICS. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available ICS Caution should be exercised when considering administration of SYMBICORT in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT Immediate hypersensitivity reactions may occur, as demonstrated by cases of urticaria, angioedema, rash, and bronchospasm Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension Long-term use of ICS may result in a decrease in bone mineral density (BMD). Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating SYMBICORT and periodically thereafter ICS may result in a reduction in growth velocity when administered to pediatric patients Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of ICS, including budesonide, a component of SYMBICORT. Close monitoring is warranted in patients with a change in vision or history of increased intraocular pressure, glaucoma, or cataracts In rare cases, patients on ICS may present with systemic eosinophilic conditions SYMBICORT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, pharyngitis, rhinitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis The most common adverse reactions ≥3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection SYMBICORT should be administered with caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents Beta-blockers may not only block the pulmonary effect of beta-agonists, such as formoterol, but may produce severe bronchospasm in patients with asthma ECG changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with concomitant beta-agonists. Use caution with the coadministration of SYMBICORT INDICATIONS SYMBICORT is indicated for the treatment of asthma in patients 6 years and older not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA (also see DOSAGE AND ADMINISTRATION). SYMBICORT 160/4.5 is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and to reduce COPD exacerbations. SYMBICORT is NOT indicated for the relief of acute bronchospasm. Please see full Prescribing Information, including Patient Information. You may report side effects related to AstraZeneca products. Notes About Asthma Asthma is a chronic, inflammatory respiratory disease with variable symptoms that affects as many as 262 million people worldwide,1 including approximately 25 million in the US.2 Patients with asthma experience recurrent breathlessness and wheezing, which varies over time, and in severity and frequency.3 These patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.4-5 There are an estimated 136 million asthma exacerbations globally per year,6 including approximately 10 million in the US2; these are physically threatening and emotionally significant for many patients7 and can be fatal.3,8 Inflammation is central to both asthma symptoms4 and exacerbations.9 Many patients experiencing asthma symptoms use a SABA (e.g., albuterol) as a rescue medicine10-12; however, taking a SABA alone does not address inflammation, leaving patients at risk of severe exacerbations,13 which can result in impaired quality of life,14 hospitalization15 and frequent oral corticosteroid (OCS) use.15 Treatment of exacerbations with as few as 1-3 short courses of OCS are associated with an increased risk of adverse health conditions including type 2 diabetes, depression/anxiety, renal impairment, cataracts, cardiovascular disease, pneumonia and fracture.16 International recommendations from the GINA no longer recommend SABA alone as the preferred rescue therapy.3 About COPD COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.17 Affecting an estimated 16 million Americans, COPD is the third leading cause of death due to chronic disease and the sixth overall leading cause of death in the US.18-19 About AIRSUPRA® AIRSUPRA (albuterol and 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. 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. About BEVESPI AEROSPHERE® BEVESPI AEROSPHERE (glycopyrronium and formoterol fumarate) is a fixed-dose dual bronchodilator in a pMDI, combining glycopyrronium, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-agonist (LABA). PMDIs are an important choice for COPD patients where limited lung function, advanced age and reduced dexterity or cognition are significant considerations for patients to achieve therapeutic benefits from their medicines. BEVESPI AEROSPHERE is the only LABA/LAMA with Aerosphere delivery technology. Results from an imaging trial have shown that BEVESPI AEROSPHERE effectively delivers medicine to both the large and small airways. About BREZTRI AEROSPHERE® BREZTRI AEROSPHERE (budesonide, glycopyrrolate, and 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 in a pressurized 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. About SYMBICORT® Symbicort (budesonide and formoterol fumarate dihydrate) is the number one ICS/LABA combination therapy in asthma and chronic obstructive pulmonary disease (COPD) in China. It is a combination formulation containing budesonide, an ICS that treats underlying inflammation, and formoterol, a LABA with a fast onset of action, in a single inhaler. Symbicort was launched in 2000 and is approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbuhaler or Symbicort pMDI (pressurised metered-dose inhaler). About AstraZeneca in 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. 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. Please visit and follow us on social media @AstraZeneca. About AZ&Me™ AstraZeneca’s patient assistance program, AZ&Me Prescription Savings Program (AZ&Me), is part of the Company’s commitment to addressing barriers to access and affordability to improve medication adherence, enhance patient care, and help patients lead healthier lives. AZ&Me is just one of the ways that AstraZeneca makes its life-changing medicines widely available, accessible, and affordable. For over 40 years, AstraZeneca has offered a patient assistance program through AZ&Me and prior legacy free drug programs, making it one of the longest standing patient assistance programs in the country. Since 2007, over five million people have benefited from this program. In addition to its patient assistance programs, AstraZeneca offers other affordability programs and resources to help increase patients’ access to medicines and reduce their out-of-pocket costs including a co-pay savings program for commercially-insured patients and additional affordability resources. Each of these programs offer financial support to particular patient populations, consistent with applicable legal requirements. The goal of AZ&Me is to help patients who have been prescribed an AstraZeneca medication and are having difficulty affording it. Patients enrolled in AZ&Me receive their AstraZeneca medicine for free. To learn more, visit AZ&Me.com. References The Global Asthma Report 2022. Accessed: March 2024. Centers for Disease Control and Prevention (CDC). Most Recent National Asthma Data. Accessed: March 2024. Global Initiative for Asthma. Updated May 2023. Accessed: March 2024. Price D, et al. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009. Papi A, et al. Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2018;6(6): 1989-1998.e3. Data on File. REF-173201. AstraZeneca Pharmaceuticals LP. Sastre J, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016;9:13. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014;40(4):364-372. Wark PA, et al. Asthma exacerbations. 3: Pathogenesis. Thorax. 2006;61(10):909-915. Johnson DB, et al. Albuterol. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan 10. Montemayor T, et al. Albuterol: Often Used and Heavily Abused. Respiratory Care. November 2021, 66 (Suppl 10) 3603775. ClinCalc.com. Albuterol Drug Usage Statistics, United States, 2013-2020. Accessed: March 2024. Nwaru BI, et al. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020;55(4):1901872. Lloyd A, et al. The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Prim Care Respir J. 2007;16(1):22-27. Bourdin A, et al. ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions. Eur Respir J. 2019;54(3):1900900. Price DB, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193-204. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. [Online]. Accessed: March 2024. National Heart, Lung, and Blood Institute. What is COPD? Accessed: March 2024. Centers for Disease Control and Prevention. Leading Causes of Death. Accessed: March 2024. # US-87197 Last Updated 3/24 View source version on businesswire.com: Contacts Brendan McEvoy +1 302 885 2677 Jillian Gonzales +1 302 885 2677 US Media Mailbox: usmediateam@astrazeneca.com Source: AstraZeneca View this news release online at:

ReOpen was the first ever large placebo-controlled clinical trial program to demonstrate statistically significant reduction of symptoms in chronic sinusitis patients without nasal polyps Clinical trial program also showed reduction in sinus inflammation and in acute exacerbations, which frequently result in use of antibiotics XHANCE uses the proprietary Exhalation Delivery System to enable deposition of a proven steroid in target areas of inflammation deep in the nose not typically reached by standard nasal sprays Chronic sinusitis affects approximately 30 million adults in the U.S. YARDLEY, Pa., March 15, 2024 (GLOBE NEWSWIRE) -- Optinose (NASDAQ:OPTN), a pharmaceutical company focused on patients treated by ear, nose and throat (ENT) and allergy specialists, today announced the U.S. Food and Drug Administration (FDA) has approved XHANCE® (fluticasone propionate) nasal spray for the treatment of chronic rhinosinusitis without nasal polyps in patients 18 years of age and older. Chronic sinusitis (also called “chronic rhinosinusitis” or “CRS”) is one of the most common chronic diseases, affecting approximately 30 million adults in the United States. Research shows that the disease impairs quality of life to a similar degree as other serious chronic conditions, such as chronic obstructive pulmonary disease, sciatica, or migraine. Chronic sinusitis is also one of the most common diagnoses in adult outpatient medicine. Chronic sinusitis is diagnosed in approximately 10 million outpatient visits, of which approximately 70% result in antibiotic prescriptions, and leads to more than 600,000 surgeries annually. Although there are FDA–approved medications to treat nasal polyps, including XHANCE, no medication had ever been approved for the more than two-thirds of chronic sinusitis patients who do not have nasal polyps – until today.1 “The FDA approval of XHANCE for the treatment of CRS without nasal polyps is an important milestone,” said Rick Chandra, M.D., Professor of Otolaryngology-Head and Neck Surgery, Endowed Director, Roland “Ron” Eavey, MD, SM Endowed Directorship in Leadership and Education, Service Chief, Rhinology and Skull Base Surgery, Vanderbilt University. “Until today, we have been forced to use unproven therapies to try and alleviate the symptoms that these patients suffer. While we often resort to using nasal steroid sprays in this patient population, they have never been shown to be effective in large placebo-controlled clinical studies. XHANCE, which uses the Exhalation Delivery System to enable delivery of an established topical steroid to the areas of the nasal cavity and sinuses we know to be extensively inflamed, is now proven to be effective in treating our CRS patients both with and without nasal polyps.” “People who don’t suffer from chronic sinusitis may not appreciate how burdensome the condition can be. More than 80% of patients with chronic sinusitis report frustration with symptom relief when using a standard-delivery nasal steroid sprays, and patients commonly use multiple unproven over the counter medications in an effort to find symptom relief.” said Ramy Mahmoud, MD, MPH, CEO of Optinose. “Although chronic sinusitis is one of the most common diagnoses in outpatient physician visits, and surgery is available, there has never been a prescription medication approved by the FDA as safe and effective to treat the millions of patients without nasal polyps suffering from this debilitating disease. We are thrilled to now be able to offer new hope to these patients and believe XHANCE has the potential to become part of the standard of care for the treatment of chronic sinusitis.” The approval was based on data from the ReOpen program evaluating XHANCE for treatment of adults with chronic sinusitis. A drug-device combination product, XHANCE uniquely combines a widely used nasal steroid with the Exhalation Delivery System™, an innovative delivery system designed to target the sites where inflammation occurs, especially difficult-to-access sinuses and sinonasal drainage tracts not typically reached by standard-delivery nasal sprays. The safety pro tolerability of XHANCE for patients in the ReOpen trials was generally consistent with its currently labeled safety profile. The most common adverse reactions (incidence ≥ 3%) in the ReOpen program were epistaxis, headache, and nasopharyngitis. About Optinose Optinose is a global specialty pharmaceutical company focused on serving the needs of patients cared for by ear, nose and throat (ENT) and allergy specialists. To learn more, please visit or follow us on X and LinkedIn. About XHANCE XHANCE® is a drug-device combination product that uses the Exhalation Delivery System™ (also referred to as the EDS®) designed to deliver a topical steroid to the high and deep regions of the nasal cavity where sinuses ventilate and drain. XHANCE is approved by the U.S. Food and Drug Administration for the treatment of chronic rhinosinusitis (with and without nasal polyps) in patients 18 years of age or older. About the ReOpen Program The ReOpen program comprised two global, randomized, double-blind, placebo-controlled Phase 3 trials that evaluated the efficacy and safety of one or two sprays of XHANCE in each nostril twice daily, over 24 weeks, in patients suffering from chronic sinusitis. In ReOpen1, the first of the two trials, 332 chronic sinusitis patients either with or without concurrent nasal polyps were treated. In ReOpen2, 222 chronic sinusitis patients who did not have polyps in the nasal cavity were treated. The co-primary endpoints were change from baseline in symptoms, as measured by composite symptom score (nasal congestion, facial pain or pressure, and nasal discharge) at the end of week 4, and change in inflammation inside the sinus cavities, as measured by CT scans (change in the average of the percentages of volume occupied by disease in the ethmoid and maxillary sinuses) at week 24. The ReOpen trial program is a landmark research program that included the first ever large, placebo-controlled trials we are aware of to demonstrate that any nasal medication produces significant improvement in both symptoms and inflammation inside the sinuses for patients with chronic sinusitis, regardless of whether or not nasal polyps are present, and to show reduction in the number of acute exacerbations.1 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE. WARNINGS AND PRECAUTIONS: Local nasal adverse reactions, including epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing, can occur. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred. Glaucoma and cataracts may occur with long-term use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use XHANCE long-term. Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur. Immunosuppression and infections can occur, including potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly. Assess for decrease in bone mineral density initially and periodically thereafter. ADVERSE REACTIONS: Chronic rhinosinusitis without nasal polyps: The most common adverse reactions (incidence ≥3%) are epistaxis, headache, and nasopharyngitis. Chronic rhinosinusitis with nasal polyps: The most common adverse reactions (incidence ≥3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis. DRUG INTERACTIONS: Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects. USE IN SPECIFIC POPULATIONS: Hepatic impairment. Monitor patients for signs of increased drug exposure. Please see full Prescribing Information, including Instructions for Use References James N. Palmer, Nithin D. Adappa, Rakesh K. Chandra, Greg E. Davis, Mahboobeh Mahdavinia, John Messina, Randall A. Ow, Zara M. Patel, Anju T. Peters, Harry Sacks, Rodney J. Schlosser, Raj Sindwani, Zachary M. Soler, Andrew A. White, Sarah K. Wise, Ramy A. Mahmoud, Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), The Journal of Allergy and Clinical Immunology: In Practice, 2024,, ISSN 2213-2198, ( ) Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, statements relating to the benefits of XHANCE for the treatment of chronic sinusitis (also called chronic rhinosinusitis) with and without nasal polyps; the benefits of the approval of XHANCE for the treatment of chronic rhinosinusitis without nasal polyps; the potential for XHANCE to become part of the standard of care for the treatment of chronic sinusitis; the benefits of the Exhalation Delivery System; and other statements regarding the Company's future operations, prospects, objectives, and other future events. Forward-looking statements are based upon management’s current expectations and assumptions and are subject to a number of risks, uncertainties and other factors that could cause actual results and events to differ materially and adversely from those indicated by such forward-looking statements including, among others: physician and patient acceptance of XHANCE for its new indication (treatment of adults with chronic rhinosinusitis without nasal polyps); the Company’s ability to maintain adequate third party reimbursement for XHANCE (including its new indication); potential for varying interpretation of clinical trial results of XHANCE for the treatment of chronic sinusitis; ; the prevalence of chronic sinusitis and market opportunities for XHANCE may be smaller than the Company expects; and the risks, uncertainties and other factors discussed under the caption "Item 1A. Risk Factors" and elsewhere in our most recent Form 10-K and Form 10-Q filings with the Securities and Exchange Commission - which are available at . As a result, you are cautioned not to place undue reliance on any forward-looking statements. Any forward-looking statements made in this press release speak only as of the date of this press release, and we undertake no obligation to update such forward-looking statements, whether as a result of new information, future developments or otherwise. Optinose Investor Contact Jonathan Neely jonathan.neely@optinose.com 267.521.0531

Hyloris Reports Full Year Results for 2023 & Provides Business Outlook Total revenue and other income amounted to €4.4 millionStronger growth expected in 2024 of both sales and gross margin, mainly fueled by the recent launch in the U.S. of Maxigesic® IV and Podofilox gel, the global roll out of Maxigesic IV® and commercial dealsIncreased operating R&D expenses while net operating cash outflow remained stable versus 2022Significant R&D progress including clinical and regulatory achievements with multiple NDA submissions expected within the next 15 monthsAttractive commercial deals, including an out-licensing deal for Atomoxetine Oral Liquid in CanadaPromising new product candidates driving innovation, targeting a portfolio of 30 assets by 2025€30.2 million in cash & cash equivalents, no financial debtWebcast on 14 March 2024 at 1PM GMT / 2PM CET/ 9AM EST (Register here) Liège, Belgium – 14 March 2023 – 7AM CET – Regulated Information – Inside Information - Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announces its financial and operational results for the year ending on 31 December 2023, as well as its business outlook for 2024. Stijn Van Rompay, Chief Executive Officer of Hyloris, commented: “Despite a challenging year for the global healthcare industry, 2023 proved to be a year of significant accomplishment for Hyloris. As a company built on the unique and successful strategy of repurposing and reformulating existing pharmaceuticals, we achieved a major milestone with the U.S. approval of Maxigesic® IV in partnership with AFT Pharmaceuticals, marking a crucial step in delivering this innovative pain management solution to American patients. Additionally, approval was secured for Podofilox gel, the first generic version of Condylox® Gel, expanding access to this medication. Our unwavering commitment to research and development yielded impressive progress across our diverse product pipeline. These advancements solidify our position as a leader in providing solutions to unmet medical needs in the years to come. We are incredibly proud of our team's dedication and resilience throughout this transformative year. Looking ahead to 2024, Hyloris is poised for continued growth and innovation. We plan to significantly bolster our pipeline with the addition of several new product candidates addressing critical unmet medical needs. Recent additions, including treatments for Vulvar Lichen Sclerosus and Burning Mouth Syndrome, demonstrate our commitment to expanding our portfolio and addressing a wider range of patient needs. We remain confident in our ability to continue delivering value to patients, shareholders, and all stakeholders and expect continued growth beyond 2024. Commercial Highlights Maxigesic® IV is a patented, unique combination, intravenous formulation for the treatment of post-operative pain and is currently licensed to partners covering over 100 countries across the globe. During 2023 and early 2024: A marketing authorization was granted by the United States Food and Drug Administration (FDA) in October 2023.Hikma Pharmaceuticals (Hikma), a leading supplier of complex injectable hospital products, has launched the product in the U.S. under the tradename Combogesic® IV. An exclusive license and distribution agreement had previously been signed between Hyloris’ partner AFT Pharmaceuticals (AFT) and Hikma.Additional submissions for marketing authorization were made in 13 countries in the Middle East, Africa, Latin America, and Asia.Additional marketing authorizations have been granted in 8 countries including Poland, South Africa, and Spain. In early 2024, Health Canada granted approval bringing the total number of approvals to 50.Launches occurred in 14 countries including Norway, Singapore, Belgium, The Netherlands, the Czech Republic, and Romania. Imminent launches are expected in several additional countries, bringing the total number of countries where Maxigesic® IV will be available up to more than 30. In the United States, chronic opioid usage in patients following surgery averages around 9%, ranging from 4% to 24% among various specialties. Drug overdoses involving opioids resulted in over 80.000 deaths in the U.S. in 2021. Patients who experienced an opioid overdose accounted for nearly $2 billion in annual hospital costs. Sotalol IV is a patented, intravenous formulation of Sotalol for the treatment of atrial fibrillation, and life-threatening ventricular arrhythmias developed for the U.S. Sotalol IV potentially allows to significantly reduce the length of hospital stay and the overall cost of care and potentially improve patient outcomes. Hyloris is taking further steps targeting to increase product related revenues in the future (see also: Ongoing Legal Proceedings). Podofilox Gel (Product previously referenced as HY-016) In December 2023, our partner Padagis US LLC (Padagis) received marketing authorization for Podofilox gel 0.5% from the FDA. Padagis launched the product in December 2023. It is the first generic for Condylox® Gel in the U.S. Podofilox Gel is an antimycotic drug for the topical treatment of external genital and perianal warts caused by certain types of the Human Papilloma Virus (HPV). Around 1% of the sexually active population in the U.S. presents with genital or perianal warts.1 To date there is a vaccine for HPV but no cure. For the 12 months period ending December 2022, Condylox® Gel had U.S. sales of approximately $9 million according to IQVIA Health. Other Commercial Highlights Tranexamic Acid RTU Additional out-licensing agreements were signed for Tranexamic Acid RTU in 2023. These agreements cover a large European country and several major Asian countries, with a combined population of over 60 million people. Previous agreements have been signed in 2021 for Australia, New-Zealand and Canada. In 2023, our licensing partner for Canada submitted an application for approval by Health Canada. Additional regulatory submissions in the partnered territories are in progress, and more out-licensing agreements are expected going forward. An Abbreviated New Drug Application (ANDA) has been submitted to the U.S. FDA. Tranexamic acid injection is an established antifibrinolytic agent used in emergency situations with major hemorrhages and is also used as a prophylactic agent in surgeries. Hyloris is developing a ready-to-use (RTU) formulation for infusion. Atomoxetine Oral Liquid An out-licensing agreement was signed with Kye Pharmaceuticals (Kye) in October 2023. Kye will exclusively commercialize the product in Canada where atomoxetine is currently not available as an oral liquid formulation. The introduction of an oral liquid formulation in the ADHD (Attention Deficit Hyperactivity Disorder) medication category has historically led to significant market share gains2. This suggests a strong potential for Atomoxetine Oral Liquid in Canada, where an estimated 1.8 million people (or 4-6% of adults and 5-7% of children) are diagnosed with ADHD3. ADHD is a chronic condition, with symptoms persisting into adulthood for 60-80% of patients4. Under the terms of the agreement, Hyloris will be eligible to receive attractive sales-related milestone payments (totaling up to USD 7.5 million), and a substantial share of the generated revenue. New Pipeline Product Candidates Our business development team leverages its expertise in existing products, real-world data, and a vast network to identify unmet medical needs. This includes collaborating with healthcare professionals, patient groups, insurers (payors), and industry partners. In 2023 over 87 opportunities were screened and 3 product candidates will meet our investment criteria of €7 million5 in 7 years or less. For product candidates which Hyloris intends to out-license, the strategic goal is to capture a substantial part of the net product margin realized by our commercial partners. Hyloris aims to achieve this by partnering these assets close to regulatory submission, except in countries where additional local clinical trials are required. In general, we will prioritize in-market product sales or profit-based participation over (upfront) milestone payments. We aim to increase our product portfolio to 30 assets by 2025, with a focus on accelerating pipeline growth in the near future. HY-091, a novel topical treatment candidate for Vulvar Lichen Sclerosus (VLS) was announced in January 2024. VLS is a chronic inflammatory condition affecting an estimated 3% of women, causing severe pain, itching, and discomfort, significantly impacting their quality of life. HY-091 is being developed as a convenient and user-friendly treatment specifically designed to target these VLS symptoms. Hyloris has partnered with AFT for co-development, registration, and worldwide commercialization. HY-090, a promising new treatment candidate for Burning Mouth Syndrome (BMS) was announced in December 2023. BMS is a chronic condition affecting millions, primarily postmenopausal women, causing a burning, tingling, or scalding sensation in the mouth for months at a time. While the mouth appears healthy, sufferers may also experience dry mouth or taste alterations, the exact cause of BMS remains unknown. Studies suggest that 0.7% to 5% of individuals in the U.S. might be affected6. Hyloris has partnered with AFT to co-develop and commercialize the product worldwide. HY-088 was announced in January 2023. This novel, proprietary oral formulation will be administered to patients with hypophosphatemia – a condition where the blood level of phosphorus is lower than 2.5mg/dL. Patients can develop hypophosphatemia from either a genetic abnormality (such as Cushing Syndrome or osteomalacia) or an acquired condition (like long-term use of diuretics or phosphate binders). It is estimated hypophosphatemia affects around 5% of hospitalized patients, and a subpopulation needs direct treatment during and/or after their hospital stay. Treatment protocols for patients deficient in phosphate are well-established and have proven useful in other situations of bone mineral imbalance. Oral administration is the preferred way of treating hypophosphatemia, although in most countries no approved drugs exist. Currently, physicians mostly rely on compounded drugs which have, by definition, not been submitted for regulatory scrutiny regarding safety, efficacy, and quality. R&D Update Throughout 2023, Hyloris achieved significant advancements across the entire R&D portfolio, propelling the 18 product candidates and 3 high-barrier generics closer to commercialization. Key milestones were met for multiple programs, and discussions with regulatory agencies and partners are underway to solidify development plans. As a result, Hyloris anticipates submitting multiple INDs (Investigational New Drug applications) and NDAs (New Drug Applications) throughout 2024 and early 2025. Enhanced Capabilities Drive Efficiency Further bolstering our R&D efforts, Hyloris officially opened its new and improved R&D lab at the Montlegia Science Park in June 2023. This on-site facility allows Hyloris to perform drug formulation and analytical activities in-house, streamlining processes and optimizing resource allocation for the expanding pipeline. Cardiovascular Portfolio Hyloris is actively engaged in advancing a comprehensive portfolio dedicated to addressing a wide range of conditions within the largest global treatment category – cardiovascular care. These products are currently progressing through or towards clinical trials, with the aim of significantly enhancing the quality of life for patients. Main highlights for 2023 and selected expected milestones for 2024 include: Aspirin IV: Registration batches have been manufactured and the stability study is ongoing. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. Aspirin IV is an intravenous (IV) formulation of acetylsalicylic acid (ASA) to be used in an emergency setting. Aspirin is not available in the U.S. as an IV product. Currently, most patients suspected of having an emergency cardiovascular event (such as a myocardial infarction or stroke) are immediately given oral aspirin to decrease their risk of morbidity and mortality. Milrinone: The optimization of the extended-release formulation for alcohol resistance marked a significant development milestone. Preparations for a pilot pharmacokinetic (PK) study are in progress. Oral milrinone is being developed as a novel, extended-release formulation offering convenient oral dosing for a selected population of end-stage heart failure (HF) patients who have Left Ventricular Assist Devices (LVADs). HY-074: All non-clinical studies were completed in 2023. A patent application was filed through the Patent Cooperation Treaty (PCT) which allows an applicant to seek patent protection in several different countries – including the U.S. Hyloris is targeting an IND submission for Q2 2024 for the PK bridging study expected to start at the end of 2024. HY-074 is an intravenous formulation of current standard of care treatment for acute coronary syndrome (ACS) to offer faster onset of action, more convenient administration, and dosage control. It is currently available in oral form, which should allow for an optimal switching strategy from the oral form to an IV in a hospital setting. Dofetilide IV: Registration batches have been manufactured and the stability study is ongoing. A CRO has been selected for the required clinical study. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. A pivotal clinical study to support regulatory submission for Dofetilide IV is nearing completion, with results expected by Q3 2024. Additional U.S. patent applications have been filed to bolster the drug's intellectual property protection. Other Value-Added Programs Hyloris, in collaboration with its development partners, is achieving consistent progress on all stages of our value-added programs. Main highlights for 2023 and expected milestones for 2024 include: Tranexamic Acid Oral Mouth Rinse (previously HY-004): A Type A meeting with the FDA resulted in alignment on the phase 3 study protocol. The phase 3 trial began in November 2023, enrolling the first patient in early 2024. Completion of enrollment (Last Patient Last Visit - LPLV) is expected by year-end, with study results anticipated in the first half of 2025. This rinse targets patients on blood thinners (anticoagulant therapies) undergoing dental procedures with a high risk of excessive bleeding. Additionally, Hyloris intends to explore the effectiveness in a wider range of related oral surgery procedures, encompassing both patients with and without bleeding disorders who could benefit from a localized treatment to reduce blood clotting. Miconazole/Domiphen Bromide: Hyloris is co-developing Miconazole/Domiphen Bromide (MCZ/DB) with Purna Female Healthcare, a topical cream combining miconazole and domiphen bromide. This innovative treatment targets Recurrent Vulvovaginal Candidiasis (rVVC), a chronic and often debilitating vaginal yeast infection affecting nearly 1 in 10 women throughout their lives. The Phase 2 clinical trial, completed in late 2023 (Q4), showed promising results. The low-dose group exhibited evidence of delayed disease recurrence at day 29. These findings will be used to design the next clinical trial, scheduled to begin by year-end 2024. MCZ/DB presents a strong scientific and commercial potential for addressing rVVC. AlenuraTM: Hyloris is co-developing Alenura™ with Vaneltix. It is a first-in-class drug candidate designed to bring immediate pain relief to patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS). This chronic condition affects at least 6 million people in the U.S. alone. Alenura™ stands out for its innovative dual mode-of-action. It combines a new, alkalinized form of lidocaine for fast pain relief with heparin to potentially aid in the regeneration of the bladder lining. This unique approach holds promise for providing both immediate symptom relief and long-term benefits for IC/BPS patients. June 2023 marked a significant milestone with the enrollment of the first patient in the Phase 2 clinical trial of Alenura™. This pivotal study will compare the effectiveness of Alenura™ against its individual components (lidocaine and heparin) as well as a placebo. PTX-252: PTX-252 is a novel chelating agent in development for the treatment of Acute Myeloid Leukemia (AML). This product candidate incorporates a novel molecular entity that is a derivative of a known established molecule. This advancement was followed by positive news: Hyloris' co-development partner, Pleco, secured Orphan Drug Designation from the FDA for PTX-252 specifically for AML. PTX-252's potential lies in its ability to potentially improve the effectiveness of existing chemotherapy for AML patients. This is particularly significant as AML affects approximately 160,000 people globally. Previous research suggests a correlation between high levels of toxic metals and lower survival rates in AML patients. A Pre-Investigational New Drug (PIND) meeting with the FDA is planned. Valacyclovir: A successful study demonstrating bioequivalence was completed in 2023. An additional pivotal study can be expected to start and close in H1 of 2024. Registration batches have been manufactured to demonstrate pharmaceutical quality of the product and robustness of the manufacturing process. Hyloris is developing a liquid formulation of valacyclovir which is currently only available in oral solid form. Valayclovir is an antiviral drug commonly used to treat the Herpes Simplex Viruses (HSV) that cause cold sores, genital herpes, chicken pox, and shingles. Management & Board changes The total headcount of the Company grew to 42 people, with several key recruitments occurring over the summer. To enhance the development activities, only limited additional hiring is required. Both the C-level executives and all board members remained in their respective positions, providing continuity in the company's leadership. Business Outlook With 18 reformulated and repurposed molecules, and 3 high-barrier generics, several clinical trials are expected to start and/or finish within 2024. The Company is actively accelerating the growth of its product pipeline, aiming to reach 30 product candidates by 2025. The company is expecting several clinical and regulatory achievements in the next 15 months. Several clinical studies will be initiated or completed. The Company is anticipating multiple NDA submissions to the U.S. FDA and other regulatory agencies. Webcast Details The Company will host a webcast conducted in English to present its 2023 annual results and 2024 Business Outlook, followed by a live Q&A session. The webcast will start on March 14th 2024 at 2PM CET / 1PM GMT / 9AM EST. To join the webcast, please register at the following link: Hyloris: 2023 Full Year Results, Outlook for 2024, and Q&A For those unable to join via webcast, please find dial in information below: Phone Conference ID: 598 167 742# Belgium: +32 4 290 22 87France: +33 1 73 24 00 56Netherlands: +31 20 708 1382Switzerland: +41 43 434 66 31United Kingdom: +44 20 7660 8327United States: +1 347 378 4531Japan: +81 3 4540 5088 Financial Highlights 2023 Year ended 31 December (in € thousand)20232022 Restated*VarianceTotal Revenues and Other income4,4062,38685%Revenues2,8141,951*44%Other operating income1,5924357266%Operating expenses(20,642)(14,024)47%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)44%General and administration expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating result (EBIT)(16,236)(11,638)*40%Net financial result474(127)-473%Income Taxes-(4) Profit/(Loss) for the period(15,762)(11,770)*34%Net operating cash flow(12,726)(12,499)82%Other investment-10,000 Cash and cash equivalents30,19633,457-10%Total cash and Other investment30,19643,457 *See Note: Restatement of the year 2022 and Press Release dated 14th of March 2024 related to restatement for additional information on HY-038 and HY-088. Total Revenue and Other Income In 2023, total revenue and other income increased to €4,406 thousand compared to €2,386 thousand in 2022, which is 85% higher compared to last year. The strong growth is mainly driven by increase of royalties of the 3 early-stage commercialized products, services provided to external partners and non-dilutive funding which we received from a US State Government and the Walloon region in Belgium. Results The Company realized a net loss of €15,762 thousand in 2023, compared to a net loss of €11,770 thousand last year. The net loss is mainly resulting from the increase in R&D expenditure and G&A expenses for supporting the development of the Company. R&D expenditure during 2023 amounted to €14,749 thousand, compared to €10,272 thousand in 2022. The increase was mainly driven by the progressive shift from early to late-stage development of several product candidates as well as the increased headcount of the research and development team leading to additional costs. General and administrative expenses increased to €5,653 thousand in 2023 versus €3,517 thousand in 2022, mainly driven by higher legal costs related to the AltaThera’s litigation compared to last year. The net financial income in 2023 was €474 thousand compared to a net financial loss of €127 thousand in 2022. The positive evolution of the financial result is mainly due to the impact of an active cash management strategy in a context of high short term interest rates both in EURO and USD. As a result, net losses in 2023 increased to €15,762 thousand versus €11,770 thousand in the same period of 2022. Balance Sheet The Company’s non-current assets mainly consist of (1) investments in joint ventures of € 3,801 thousand, (2) intangible assets of €3,828 thousand including capitalized development, purchased assets and in-licensing costs, versus €3,600 thousand in 2022, (3) Right of use assets related to the leasing of the office, lab and cars, (4) shares in Pleco of €1,000 thousand, (5) a prepayment of future royalties to a third party of $700 thousand and (6) a tax credit. Hyloris does not capitalize research and development expenses until the filing for a marketing authorization for the applicable product candidate. Research and development expenditures incurred during the period were accounted for as operating expenses. When an intangible asset is acquired and capitalized, the amortization begins when the asset is available for commercialization. The Company’s current assets mainly consist of €30,196 thousand in cash and cash equivalents on total assets of €47.61 million, and trade and other receivables of €4.1 million. The increase in Right-of-use assets and borrowings is due to the start of the lease for the new lab. The Company received an advance payment related to a government grant from the Walloon region. €43 thousand of this advance is a financial liability and €37 thousand is part of Trade and other liabilities. Cash Position and cash flow The Company maintains its strong cash position, with a current cash and cash equivalents totaled €30,196 thousand at the end of 2023, compared to €43,457 thousand at the end of 2022 (which includes a deposit for an amount of €10 million which has been reclassified to Other investment in 2022). Net cash outflow generated from operating activities was €12,726 thousand in 2023, compared to a net operating cash outflow of €12,499 thousand in 2022. The stable net operating cash outflow is attributed to an internal control system implemented to oversee expenditure and cash flow, which includes effective management of working capital. CONSOLIDATED STATEMENT OF FINANCIAL POSITION FOR THE YEAR ENDED DECEMBER 31 ASSETS (in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Non-current assets12,33611,063 Intangible assets3,8283,607 Property, plant and equipment429176 Right-of-use assets1,724885 Equity accounted investments3,8013,948 Other investment, including derivatives1,0001,000 Trade and other receivables1.5541.447 Current assets35,27649,801 Trade and other receivables4,1004,127 Other investment, including derivatives49910,4699 Prepayments4811,748 Cash and cash equivalents30,19633,4579 TOTAL ASSETS47,61260,864 EQUITY AND LIABILITIES(in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Equity 38.82254.045 Share capital140140 Share premium121,513121,513 Retained earnings, excluding profit (loss) for the reporting period(65,246)(53,476) Result of the period, profit (loss) for the reporting period(15,762)(11,770) Share based payment2.1611,621 Cost of Capital(4,460)(4,460) Other reserves476476 Non-current liabilities1.8531,047 Borrowings1,510747 Other financial liabilities344300 Current liabilities6,9375,772 Borrowings241138 Other financial liabilities3,2003,212 Trade and other liabilities3,4962,422 Current tax liabilities-- TOTAL EQUITY AND LIABILITIES47,61260,864 CONSOLIDATED STATEMENT OF PROFIT OR LOSS AND OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED DECEMBER 31 in € thousands20232022 restated*VarianceRevenue 2,8141,95147%Other operating income1,5924353252%Operating income4,4062,38685%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)1044%Selling, general and administrative expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating expenses(20,642)(14,024)47%Operating profit/(loss) (EBIT)(16,236)(11,638)40%Financial income86746686%Financial expenses(393)(594)-34%Profit/(loss) before taxes(15,762)(11,766)34%Income taxes-(4) PROFIT/(LOSS) FOR THE PERIOD(15,762)(11,770)34% CONSOLIDATED STATEMENT OF CHANGES IN EQUITY FOR THE YEAR ENDED DECEMBER 31 2023 (in thousands of euros) Attributable to equity holders of the CompanyTotal EquityShare capital Share premium Other reservesRetained earnings Share-based payment reserveCost of CapitalOther reservesBalance at December 31, 2021129103,6932,391(3,827)476(54,805)48,056Private Placement Via an Accelerated Bookbuild Offering514,995 (634) 14,366Equity Transaction via Transaction Warrants 62,826(1,329) 1,3292,832Share-based payments 560 560Total comprehensive income (11,770)(11,770)Balance at December 31, 2022140121,5131,622(4,460)476(65,246)54,045Share-based payments 539 539Total comprehensive income (15,762)(15,762)Balance at December 31, 2023140121,5132,161(4,460)476(81,008)38,822 CONSOLIDATED STATEMENT OF CASH FLOWS FOR THE YEAR ENDED DECEMBER 31 2023 in € thousands20232022 Restated* CASH FLOW FROM OPERATING ACTIVITIES Net result(15,762)(11,770) Adjustments to reconcile net loss to net cash provided by operating activities: Depreciation, amortisation and impairments349196 Share-based payment expense539560 Derivatives financial instruments(52)52 Interest income on deposits and current accounts-164 Net finance result(474)- Change in fair value of financial assets311- Loss on derecognition of shareholders loans-486 Equity transaction costs-29 Share of profit of equity-accounted investees, net of tax147130 Losses on disposal of PPE-16 Other non-cash adjustments(17)16 Changes in working capital: Trade and other receivables(293)(921) Other investment, including derivatives(31)4 Prepayments1,268(650) Trade and Other liabilities1,236(468) Cash generated from operations(12,779)(12,157) Interest paid527 Income Taxes paid-(349) Net cash generated from operating activities(12,726)(12,499) CASH FLOW FROM INVESTING ACTIVITIES Interest received403 Purchases of property, plant and equipment(298)(101) Purchases of Intangible assets(425)(638) Acquisition of Other Investments(0)(500) Loans made to third parties- (655) Deposits10,000(10,000) Discontinued operations Net cash provided by/(used in) investing activities9,654(11,894) CASH FLOW FROM FINANCING ACTIVITIES Reimbursements of borrowings and other financial liabilities(12)(7,376) Proceeds from borrowings and other financial liabilities44- Reimbursements of lease liabilities(222)(79) Modifications/terminations Right of Use Assets2- Proceeds from Private Placement via Accelerated Book Building- 14,337 Proceeds from Execution Transactions Warrants-2,832 Interests paid-(1,877) Net cash provided by/(used in) financing activities(188)7,838 NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS(3,261)(16,555) CASH AND CASH EQUIVALENTS at beginning of year33,45750,012 CASH AND CASH EQUIVALENTS at end of year, calculated30,19633,457* RESTATEMENT OF THE YEAR 2022 and HALF-YEAR 2023 Accounting treatment of the transactions with Qliniq Hyloris initially recognized (a) €1 million in revenue in 2022 from the divestment of HY-038, and (b) € 1 million in R&D expenses and € 0,2 million in intangible assets in H1 2023 for the purchase of HY-088. A reassessment determined that both transactions qualify as a non-monetary exchange because negotiations and valuations occurred simultaneously. Due to the development stage of the products exchanged, the fair value of neither the asset received, nor the asset given up can be reliably determined. As a result of this reassessment, the restated financials for 2022 will reverse the €1 million revenue from the divestment of HY-038. This adjustment will also affect the half-year 2023 financial statements, resulting in a reversal of €1 million in R&D expenses for HY-088. These expenses are offset against the €1 million received by Hyloris for HY-038. (See Press Release dated 14th of March 2024 on the restatement for more information) The following tables summarize the impact of the restatement on the consolidated financial statements. Consolidated statement of financial position Per 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedCurrent assets50.801-1.00049.801Trade and other receivables5.127-1.0004.127Total assets61.864-1.00060.864 Equity55.045-1.00054.045Result of the period(10.770)-1.000(11.770)Total equity and liabilities61.864-1.00060.864 Consolidated statement of profit or loss and other comprehensive income For the year ended 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedRevenues2.951-1.0001.951Gross profit2.857-1.0001.857Operating profit/(loss) (EBIT)(10.638)-1.000(11.638)Profit (loss) before taxes(10.766)-1.000(11.766)PROFIT (LOSS) FOR THE PERIOD(10.770)-1.000(11.770)TOTAL COMPREHENSIVE INCOME FOR THE PERIOD(10.770)-1.000(11.770)For the year ended 31 December 2022(in €) Impact of correction of errorAs previously reportedAdjustmentAs restatedBasic/diluted earnings/(loss) per share(0.380)(0.035)(0.435) Consolidated statement of cash flows Even though there was an actual cash inflow of EUR 1 million from the out-licensing of HY-038 and a cash outflow of EUR 1.2 million resulting from the in-licensing of HY-088, the transactions are presented in the consolidated statement of cash flows for the year ended per December 31, 2023 (i.e., EUR 200k prepaid expenses), as this most faithfully presents the substance of the transactions. There is no impact on the consolidated statement of cash flows for the year ended per December 31, 2022, as no cash inflow occurred yet. Audit Report The statutory auditor, KPMG Bedrijfsrevisoren - Réviseurs d’Entreprises, represented by Olivier Declercq, has informed us that the audit procedures were not yet completed. ONGOING LEGAL PROCEEDINGS In August 2022, AltaThera Pharmaceuticals LLC filed a complaint before the District Court for the Northern District of Illinois against Academic Pharmaceuticals Inc, Dr. Somberg and Hyloris Pharmaceuticals, for (a.o.) alleged misappropriation of AltaThera’s trade secrets and confidential information, improper inventorship, and breach of contract, which seeks (punitive) damages and termination of the agreement whereby Hyloris licenses Sotalol IV to AltaThera (the “Litigation”). Hyloris moved to dismiss the complaint for improper service of process and lack of jurisdiction. Further, in November 2022, Hyloris initiated an arbitration against AltaThera for breach of the same licensing agreement between Hyloris and AltaThera in relation to Sotalol IV, including the failure of AltaThera to use commercially reasonable efforts in selling Sotalol IV as required under the licensing agreement, which seeks damages and termination of the licensing agreement (the “Arbitration”). AltaThera responded and counter-demanded, reasserting its claims from the Litigation. At the end of August 2023, all parties agreed to stipulate to the dismissal of the Litigation and to consolidate the Litigation and the Arbitration before the American Arbitration Association (“AAA”) in New York. Hyloris contests the claims asserted by AltaThera and, based upon Hyloris’ assessment of the documents and expert reports put forward to date by AltaThera to support its claims, Hyloris is of the view that there is no convincing evidence supporting AltaThera’s claims for liability or damages. On the other hand, Hyloris believes strongly in the merits of its claims against AltaThera, and that its position is well supported by its expert reports and other documents and evidence submitted to the arbitration panel. Arbitration hearings are scheduled in April 2024 with a final decision expected by the end of H1 2024. Hyloris remains fully confident about the outcome of this litigation in its favor. Hyloris however cannot guarantee that the outcome of the litigation, even if in its favor, may not have a negative impact on future sales of Sotalol IV. About Hyloris Pharmaceuticals SA Hyloris is a specialty biopharma company focused on innovating, reinventing, and optimizing existing medications to address important healthcare needs and deliver relevant improvements for patients, healthcare professionals and payors. The Company’s development strategy primarily focuses on leveraging established regulatory pathways, such as the FDA’s 505(b)2 pathway in the U.S or equivalent regulatory frameworks in other regions which are specifically designed for pharmaceuticals for which safety and efficacy of the molecule have already been established. This approach can reduce the clinical burden required for market entry, and significantly shorten the development timelines, leading to reduced costs and risks. Hyloris has built a broad, patented portfolio of 18 reformulated and repurposed value-added medicines that have the potential to offer significant advantages over existing alternatives. Two products are currently in early phases of commercialization in collaboration with commercial partners: Sotalol IV for the treatment of atrial fibrillation, and Maxigesic® IV, a non-opioid post-operative pain treatment. In addition to its core strategic focus, the Company has 1 approved high barrier generic product launched in the U.S. and 2 high barrier generic products in development. Hyloris is based in Liège, Belgium. For more information, visit www.hyloris.com and follow-us on LinkedIn. For more information, contact Hyloris Pharmaceuticals:Stijn Van Rompay, CEOstijn.vanrompay@hyloris.com+32 (0)4 346 02 07Jean-Luc Vandebroek, CFOjean-luc.vandebroek@hyloris.com+32 (0)478 27 68 42Jessica McHarguejessica.mchargue@hyloris.com+1 919 451 4740 Disclaimer and forward-looking statements Hyloris means “high yield, lower risk”, which relates to the 505(b)(2) regulatory pathway for product approval on which the Company focuses, but in no way relates or applies to an investment in the Shares. Certain statements in this press release are “forward-looking statements.” These forward-looking statements can be identified using forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. These statements relate to future events or the Company’s future financial performance and involve known and unknown risks, uncertainties, and other factors, many of which are beyond the Company’s control, that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law. 1 https://www-aafp-org.libproxy1.nus.edu.sg/pubs/afp/issues/2010/1115/p1209.html2 IQVIA3 https://caddac.ca/about-adhd/4 https://journals-sagepub-com.libproxy1.nus.edu.sg/doi/10.1177/10600280135106995 Not adjusted for inflation6 Based on combination of different sources: population-based study, clinical based study and key opinion leaders' estimation7 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates)8 Reclassification of the loan to third-party from Operating to Investing activities in the Cash flow statement9 Reclassification of deposit from Cash and cash equivalents to Other investment including derivatives for an amount of €10 million in 202210 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates) for an amount of €120k Attachment 20240314 Full Year Results 2023 ENG