CYP3A

Petros begins enrollment in AI integrated Human Factors Study to optimize self-screening, continuing its efforts to make STENDRA (avanafil) the first erectile dysfunction medication to achieve OTC Status (Please see important safety information below) NEW YORK, NY / ACCESSWIRE / March 19, 2024 / Petros Pharmaceuticals, Inc. (NASDAQ:PTPI), a company focused on expanding consumer access to medication through over-the- counter (OTC) drug development programs, announces it has successfully launched its artificial intelligence (AI) tool developed as a result of its collaboration with a multi-billion-dollar software developer. The tool is being integrated into the Company's web app being used for patient self-screening, which it is testing in its recently launched Human Factors study. Fady Boctor, Petros' President and Chief Commercial Officer, commented, "The utilization of AI is a logical progression as we aim to optimize the safe administration of STENDRA (avanafil), in development for OTC availability. In addition, based on our recent interaction with the FDA on our technology approach, we believe the AI component directly addresses requests made by the Agency in order to optimize selection. Ultimately, we believe the AI will help us to gather information to ensure that the patient is appropriate to receive the drug. Importantly, we continue to believe that we have sufficient funding to achieve our development goals as well as significant near-term clinical milestones for STENDRA." The Human Factors Study, which incorporates the AI tool, is designed to assess whether the web tool developed by the company can be used safely and effectively by its intended users. Subjects will be asked to perform critical tasks with the web app without any guidance from the study staff. The study is based on applicable FDA guidance for human factors studies. The outcomes from this study will further contribute to discussions with the U.S. Food and Drug Administration (FDA) regarding the need for the Additional Condition of Nonprescription Use (ACNU) with regard to the web app and the Company's endeavors to develop STENDRA into the first erectile dysfunction medication to go OTC. About Petros Pharmaceuticals Petros Pharmaceuticals is committed to the goal of becoming a leading innovator in the emerging self-care market driving expanded access to key prescription pharmaceuticals as Over-the-Counter treatment options. Currently, Petros is pursuing increased access for its flagship prescription ED therapy, STENDRA, via potential OTC designation. If ultimately approved by the FDA for OTC access, STENDRA may be the first in its class to achieve this marketing status, also establishing company know how as a proven platform for other prospective prescription therapeutics. About the OTC Pathway The process of switching a prescription medication to over the counter (OTC) first involves the design of a Drug Facts Label (DFL) that is well understood by potential consumers. Then data must show that consumers can make an appropriate decision to use or not to use the product based only upon the information on the DFL and their personal medical history. Then consumers must demonstrate that they can properly use the product based upon the information on the DFL. To accomplish these things, the FDA ordinarily requires a consumer tested OTC DFL. This testing includes conduct of iterative Label Comprehension Studies (LCS) in the general population, Self-Selection Studies (SSS) in a population interested in using the product and in specific populations who may be harmed if they use the product, and usually one Actual Use Trial (AUT) demonstrating safe and appropriate use by consumers in a simulated OTC setting. The regulations that FDA is currently finalizing introduced Additional Conditions for Nonprescription Use (ACNU) criteria that enable correct self-selection by consumers and may expand OTC access to medications that formerly could only be available by prescription. An ACNU may be an innovative computerized tool, or the additional conditions may use other approaches that support the switch process. Important Safety Information about STENDRA® (avanafil) STENDRA® (avanafil), originally launched by Auxilium Pharmaceuticals prior to that company's sale to Endo Pharmaceuticals, is an oral phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction. STENDRA is not for use in women or children. It is not known if STENDRA is safe and effective in women or children under 18 years of age. (A 100-mg and 200-mg tablet can be taken as early as ~15 minutes before sexual activity. STENDRA only works with sexual stimulation and should not be taken more than once a day. STENDRA can be taken with or without food; do not drink too much alcohol when taking STENDRA (for example, more than 3 glasses of wine or 3 shots of whiskey) as it can increase chances of side effects. Of people enrolled in clinical trials, 1.4%, 2.0%, and 2.0%, respectively, stopped taking STENDRA (50 mg, 100 mg, or 200 mg) due to side effects compared to 1.7% on placebo. STENDRA® was designed and developed expressly for erectile dysfunction. STENDRA is contraindicated with any form of organic nitrates, in patients with known hypersensitivity to any component of the tablet, and in patients who are using a guanylate cyclase stimulator. Patients should not use STENDRA if sexual activity is inadvisable due to cardiovascular status or any other reason. Before taking STENDRA tell your doctor if you have had any kind of heart issues including heart attack, heart failure, angina and irregular heartbeat or have elevated or low blood pressure. Use of STENDRA with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension. Patients should seek emergency treatment if an erection lasts greater than 4 hours. Patients should stop STENDRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss with patients the increased risk of NAION in patients with a history of NAION. Patients should stop taking STENDRA and seek prompt medical attention in the event of sudden decrease or loss of hearing. STENDRA can potentiate the hypotensive effect of nitrates, alpha blockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase STENDRA exposure. For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir and telithromycin), do not use STENDRA. Combination with Other PDE5 Inhibitors or Erectile Dysfunction Therapies is not recommended. The safety of STENDRA is unknown in patients with bleeding disorders and patients with active peptic ulceration. The use of STENDRA offers no protection against sexually transmitted diseases including HIV. Consider counseling patients on protective measures for sexually transmitted diseases. The most common adverse reactions reported with use of STENDRA include headache, flushing, nasal congestion, nasopharyngitis, and back pain. For more information about STENDRA, call 844-458-4887. If you would like to report an adverse event or product complaint, please contact us at 844-458-4887. You are encouraged to report negative side effects of prescription drugs to the FDA by calling 1-800-FDA-1088, or at . Please see the full Prescribing Information and Patient Information. Cautionary Note Regarding Forward-Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements are based upon Petros Pharmaceuticals, Inc.'s ("Petros," "we," "our," "us" or the "Company") management's assumptions, expectations, projections, intentions, and beliefs about future events. In some cases, predictive, future-tense or forward-looking words such as "intend," "develop," "goal," "plan," "predict", "may," "will," "project," "estimate," "anticipate," "believe," "expect," "continue," "potential," "opportunity," "forecast," "should," "target," "pursuit," "strategy" and similar expressions, whether in the negative or affirmative, that reflect our current views with respect to future events and operational, economic and financial performance are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. Such forward-looking statements are only predictions, and actual results and the timing of certain events and circumstances may differ materially from those described by the forward-looking statements as a result of risks and uncertainties, including, without limitation, Petros' ability to execute on its business strategy, including its plans to develop and commercialize its product candidates; Petros' ability to receive clearance from the FDA to sell STENDRA as an Over-the-Counter treatment; Petros' ability to comply with obligations as a public reporting company; Petros' ability to maintain compliance with the Nasdaq Stock Market's listing standards; risks related to Petros' ability to continue as a going concern; risks related to Petros' history of incurring significant losses; risks related to Petros' dependence on the commercialization of a single product, STENDRA®; and risks related to Petros' ability to obtain regulatory approvals for, or market acceptance of, any of its products or product candidates. Additional factors that could cause actual results to differ materially from the results anticipated in these forward-looking statements are contained in the Company's periodic reports and in other filings that the Company has or may file, with the U.S. Securities and Exchange Commission (the "SEC") under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere. The Company cautions readers that the forward-looking statements included in this press release represent our beliefs, expectations, estimates and assumptions only as of the date of hereof and are not intended to give any assurance as to future results. New factors emerge from time to time, and it is not possible for us to predict all these factors. Further, the Company cannot assess the effect of each such factor on our business or the extent to which any factor, or combination of factors, may cause actual results to be materially different from those contained in any forward-looking statement. Accordingly, you should not unduly rely on any forward-looking statements. The Company undertakes no obligation to update or revise any forward-looking statements contained in this press release, whether as a result of new information, future events, a change in our views or expectations or otherwise, except as required by federal securities laws. Contacts Investors: CORE IR ir@petrospharma.com Media: Jules Abraham CORE IR 917-885-7378 pr@coreir.com SOURCE: Petros Pharmaceuticals, Inc. View the original press release on accesswire.com

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:

ROCKVILLE, Md., March 13, 2024 /PRNewswire/ -- Expert Systems, a leader in AI-enabled drug discovery, proudly announces a significant milestone in partnership with Eilean Therapeutics LLC: the start of Phase 1 trial of balamenib (ZE63-0302), a highly selective inhibitor of the menin–KMT2A binding interaction, under the Clinical Trial Notification (CTN) scheme of the Australian Therapeutics Goods Administration (TGA). "Balamenib has a highly differentiated pre-clinical pro indicates important advantages over molecules in the same class in safety, tolerability and feasibility of outpatient treatment," commented Bill Farley, CBO at Expert Systems. "We are proud that our comprehensive hybrid AI-based platform has helped accelerate the development of a new promising & safe treatment for AML." Supported by Orbimed, Torrey Pines Investment, and Dr. John C. Byrd, Eilean Therapeutics is committed to leading the development of innovative therapies that significantly enhance treatment outcomes in both hematologic and solid malignancies. This effort is bolstered by leveraging Expert Systems' cutting-edge AI platform to speed up the discovery and development process. About Balamenib Balamenib (ZE63-0302) is an oral small molecule inhibitor of the menin-KMT2A interaction. In vitro studies with KMT2Ar specific cell lines and in vivo studies using xenograft models demonstrated that balamenib is a potent menin inhibitor when administered both as a stand-alone agent or in combination with other compounds used for the treatment of r/rAML, in particular with eiletoclax (ZE50-0134), and lomonitinib (ZE46-0134), Eilean Therapeutics' BCL-2 selective inhibitor and pan FLT3/IRAK4 inhibitor, respectively. Balamenib demonstrates improved safety compared to other molecules in the same class, with an absence of QTc prolongation and is neither a substrate nor inducer of cytochrome P450 3A4 metabolism. Furthermore, balamenib shows significantly reduced susceptibility to "hot spot" menin mutations currently being encountered in the clinic with other menin inhibitors. About Expert Systems, Inc. Expert Systems, Inc., an advanced accelerator platform, is equipped with a comprehensive, hybrid AI-based system that covers the entire spectrum of preclinical drug discovery and early development phases. This includes target identification, virtual screening, non-clinical and clinical pharmacology, chemical liability assessment, and toxicology. Utilizing a unique combination of proprietary and public databases, Expert Systems employs specialized software tools to evaluate the intellectual property landscape and construct a competitive drug intelligence strategy to de-risk candidate selection for rapid transition from in silico to first-in-human trials. Expert Systems has been pivotal in establishing seed and Series A companies, organizing and managing over 30 research and development programs across various financial investors and strategic partners in North America, Europe, and Australia. To learn more, visit About Eilean Therapeutics Eilean Therapeutics LLC is a cutting-edge biopharmaceutical company, established through a collaboration between Orbimed, Torrey Pines Investment, and Dr. John C. Byrd, dedicated to the identification of both best-in-class and first-in-class small molecule inhibitors targeting escape mutations in both hematologic and solid cancers. The company harnesses the Expert Systems Inc. hybrid AI platform alongside its key partners' exclusive data, chem-bio platforms, knowledge, and expertise. This enables Eilean Therapeutics to select molecular mechanisms of pathology with high clinical relevance, precisely designing and expediting the discovery and development processes for leading-edge therapies. Eilean Therapeutics is committed to leveraging its unique capabilities and platform to create novel, groundbreaking medicines for patients with hematologic and solid malignancies, marking a new era in targeted cancer therapy. For more information, visit Bill Farley CBO bfarley@expertsystems.inc