CYP11B1

Neurocrine Biosciences has announced that the US Food and Drug Administration (FDA) has accepted its two New Drug Applications (NDA) for crinecerfont, granting them Priority Review designations. The applications cover the treatment of children, adolescents, and adults with classic congenital adrenal hyperplasia (CAH). If approved, crinecerfont would represent the first new treatment for CAH in 70 years and the first-in-class therapy offering a novel mechanism of action to address this rare and serious endocrine disorder. LAS VEGAS, Sept. 30, 2024 /PRNewswire/ -- CAH refers to a rare set of inherited autosomal recessive disorders that impair hormone production in the adrenal glands, which sit on top of the kidneys. Normally, these glands produce three types of hormones: corticosteroids, mineralocorticoids, and androgens. CAH is mostly caused by mutations in the 21-hydroxylase gene, which accounts for more than 90% of cases. In rare instances, mutations in the 11-hydroxylase gene can also lead to CAH. In the 7MM, the US accounted for the highest prevalent cases of congenital adrenal hyperplasia in 2023, with around 50% of the total prevalent cases across the 7MM; these numbers are expected to increase during the forecast period (2024–2034). DelveInsight's analysis reveals that a higher prevalence of diagnosed congenital adrenal hyperplasia is observed in the 18-year-old and above age group across the 7MM. Among mutation-based congenital adrenal hyperplasia cases, 21 OHD (CYP21A2 gene mutation) represents a higher prevalence compared to 11-Beta hydroxylase (CYP11B1 gene mutation), and others. The approach to managing CAH differs significantly based on its type and severity. While CAH cannot be completely cured, it can be managed effectively. For classical CAH, treatment begins shortly after birth and continues throughout the individual's life. Those with classical CAH should work with a team of healthcare professionals, including experts in pediatric endocrinology, uro-gynecologic surgery, psychology, and genetics. With appropriate care, individuals with classical CAH can lead normal and satisfying lives. In contrast, treatment for non-classical CAH may not be necessary, depending on the severity of symptoms. The management of classic CAH focuses on three main objectives: correcting adrenal insufficiency, lowering adrenal androgens to appropriate levels, and preventing iatrogenic hypercortisolism. Hydrocortisone is the primary glucocorticoid used, administered two to three times daily with higher doses in the morning and lower doses in the evening to align with the body's natural circadian rhythm. For NC-CAH, cortisol replacement is generally unnecessary, except in specific situations such as adult women with hyperandrogenism and fertility problems, or pediatric patients experiencing rapidly advancing precocious puberty. Currently, the only medication approved in Europe for CAH treatment is EFMODY (Hydrocortisone Modified-release Hard Capsules) by Neurocrine Biosciences. Learn more about the FDA-approved congenital adrenal hyperplasia drugs @ Drugs for Congenital Adrenal Hyperplasia Treatment EFMODY replicates the natural circadian rhythm of cortisol secretion. It compensates for low cortisol levels in patients with congenital adrenal hyperplasia, aiding in the management of the condition's symptoms. Approved for use in adolescents aged 12 and older, as well as adults, EFMODY uses hydrocortisone—a glucocorticoid that affects various tissues through intracellular steroid receptors. Containing synthetic cortisol, EFMODY gradually releases it in the intestines to mimic the body's natural cortisol release, helping to restore hormone balance and alleviate condition-related issues. In May 2021, the EMA approved EFMODY for treating congenital adrenal hyperplasia in patients aged 12 and above. Diurnal launched the drug in Germany and Austria in September 2021, and later in the United Kingdom. In November 2022, Neurocrine Biosciences acquired Diurnal for approximately USD 55 million. To know more about congenital adrenal hyperplasia treatment options, visit @ New Treatment for Congenital Adrenal Hyperplasia The congenital adrenal hyperplasia pipeline is strong with many companies working in the domain. Various potential therapies that are projected to enter during the forecast period include Neurocrine Biosciences' Crinecerfont, Spruce Biosciences' Tildacerfont (SPR001), Crinetics Pharmaceuticals' Atumelnant (CRN04894), BridgeBio's BBP-631, Lundbeck's Lu AG13909, and others. Discover which therapies are expected to grab major congenital adrenal hyperplasia market share @ Congenital Adrenal Hyperplasia Market Report Crinecerfont is an investigational oral medication that acts as a selective antagonist for the corticotropin-releasing factor Type 1 receptor (CRF1). It's being developed to manage and regulate high levels of Adrenocorticotropic Hormone (ACTH) and adrenal androgens without relying on glucocorticoids, specifically for treating congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. By blocking the CRF1 receptor, Crinecerfont reduces the overproduction of ACTH, which in turn decreases the excess production of androgens seen in CAH patients. This mechanism aims to normalize hormone levels and address the root cause of the condition. In July 2024, Neurocrine Biosciences announced that the FDA has accepted its two New Drug Applications (NDAs) for crinecerfont, both with Priority Review designations. These applications are for treating classic congenital adrenal hyperplasia in children, adolescents, and adults. If approved, crinecerfont would become the first new treatment for CAH in 70 years and a pioneering therapy with a novel approach for this rare endocrine disorder. The NDAs for crinecerfont include (1) a capsule formulation (NDA# 218808) and (2) an oral solution formulation (NDA# 218820), both addressing the efficacy and safety of crinecerfont for classic CAH. The FDA has set Prescription Drug User Fee Act (PDUFA) target action dates for these applications as December 29 and December 30, 2024, respectively. The FDA has indicated it does not plan to hold an advisory committee meeting regarding these NDAs. Crinecerfont received an Orphan Drug designation (ODD) in March 2019 and a Breakthrough Therapy designation (BTD) in December 2023. The results from the CAHtalyst Phase III trial, involving both pediatric and adult patients with CAH caused by 21-OHD, were published online in The New England Journal of Medicine on June 2 and June 1, respectively, and were also presented at ENDO 2024. BBP-631 is a gene therapy in development using adeno-associated virus (AAV) to target the root cause of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This therapy aims to deliver a functional copy of the 21-hydroxylase gene directly to the adrenal glands, where hormones are produced. Animal studies have demonstrated its effectiveness in providing consistent and long-term delivery to the adrenal glands. If successful, BBP-631 could help restore natural hormone and steroid levels in people with CAH, allowing them to produce cortisol and aldosterone—something no current treatments or clinical trials can achieve. BridgeBio envisions this gene therapy as a potential solution to correct the hormonal imbalance caused by CAH. Tildacerfont is a new-generation antagonist targeting the Corticotropin-releasing factor (CRF1) receptor. It aims to significantly enhance disease management and decrease reliance on steroids for patients with classic congenital adrenal hyperplasia and other conditions associated with high ACTH levels. By binding to CRF1 receptors, tildacerfont reduces the overproduction of ACTH and, consequently, lowers the production of adrenal androgens like androstenedione in patients with CAH and Polycystic Ovary Syndrome (PCOS). In August 2024, Spruce Biosciences announced that the top-line results from the CAHmelia-204 study, which evaluates tildacerfont in adult CAH patients, and the CAHptain-205 study, which assesses the drug in both adult and pediatric CAH patients, are expected to be released in the fourth quarter of 2024. Discover more about drugs for congenital adrenal hyperplasia in development @ Congenital Adrenal Hyperplasia Clinical Trials The anticipated launch of these emerging therapies for congenital adrenal hyperplasia are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the congenital adrenal hyperplasia market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for congenital adrenal hyperplasia is expected to grow from USD 20 billion in 2023 with a tremendous CAGR of ~40% by 2034. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the disease. DelveInsight's latest published market report titled as Congenital Adrenal Hyperplasia Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the congenital adrenal hyperplasia country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The congenital adrenal hyperplasia market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of Congenital Adrenal Hyperplasia Gender-specific Cases of Congenital Adrenal Hyperplasia Age-specific Cases of Congenital Adrenal Hyperplasia Mutation-based Cases of Congenital Adrenal Hyperplasia Type-specific Cases of Congenital Adrenal Hyperplasia The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM congenital adrenal hyperplasia market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this congenital adrenal hyperplasia market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the congenital adrenal hyperplasia market. Also, stay abreast of the mitigating factors to improve your market position in the congenital adrenal hyperplasia therapeutic space. Related Reports Congenital Adrenal Hyperplasia Pipeline Congenital Adrenal Hyperplasia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key CAH companies, including Spruce Biosciences, Lundbeck, among others. Congenital Adrenal Hyperplasia Epidemiology Forecast Congenital Adrenal Hyperplasia Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and CAH epidemiology trends. Adrenal Crisis Market Adrenal Crisis Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key adrenal crisis companies including Eton Pharmaceuticals, Antares Pharma , among others. Adrenal Crisis Pipeline Adrenal Crisis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key adrenal crisis companies, including Eton Pharmaceuticals, Antares Pharma, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CHICAGO--(BUSINESS WIRE)-- Xeris Biopharma, Inc. (Nasdaq: XERS), a growth-oriented biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies, today announced that the Food and Drug Administration (FDA) granted its subsidiary Xeris Pharmaceuticals, Inc., orphan-drug exclusivity (ODE) for Recorlev® (levoketoconazole) for the treatment of adult patients with endogenous Cushing’s syndrome for whom surgery is not an option or has not been curative. As the first approval of levoketoconazole (Recorlev) for Cushing’s syndrome, Xeris is entitled to seven years of orphan-drug market exclusivity from its FDA approval date of December 30, 2021. The FDA's Orphan Drug Designation program is designed to advance the development of drugs that treat a condition affecting 200,000 or fewer U.S. patients annually. This regulatory exclusivity is in addition to the patent exclusivity under Xeris’ U.S. patents covering Recorlev and its therapeutic use, which extends to at least March 2040. “Cushing’s syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options," said Paul R. Edick, Xeris’ Chairman and CEO. “We are excited to receive this important orphan-drug exclusivity approval for Recorlev on a new therapeutic option that can address symptoms while treating the root cause of the disease for this underserved Cushing’s patient community.” Mr. Edick continued, “Recorlev is an important and welcome therapeutic option for clinicians to help manage patients with endogenous Cushing's syndrome, a severe, potentially life-threatening rare disease. The approval of Recorlev was based upon data from two positive Phase 3 studies that evaluated a combined study population of 166 patients and was shown to be effective for reducing and normalizing cortisol.” In order to serve and support this community, Xeris is committed to ensuring everyone who needs access to their therapies will receive it. Xeris has created Xeris CareConnection™ to provide a comprehensive program for patients and their caregivers throughout the treatment journey, including financial assistance, one-on-one support, and educational resources. Xeris CareConnection also supports healthcare professionals and their teams through education on access and reimbursement. For more information visit our website ( ) or contact Xeris CareConnection (available Monday–Friday from 8 a.m–7 p.m ET) at 1-844-444-RCLV (7258). About Cushing’s Syndrome Endogenous Cushing’s syndrome is a rare, serious, and potentially fatal endocrine disease caused by chronic elevated cortisol exposure—often the result of a benign tumor of the pituitary gland. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period of time, which often results in characteristic physical signs and symptoms that are distressing to patients. The disease is most common among adults between the ages of 30–50, and it affects women three times more often than men. Women with Cushing's syndrome may experience a variety of health issues, including menstrual problems, difficulty becoming pregnant, excess male hormones (androgens), primarily testosterone, which can cause hirsutism (growth of coarse body hair in a male pattern), oily skin, and acne.3 Additionally, the multisystem complications of the disease are potentially life threatening. These include metabolic changes such as high blood sugar or diabetes, high blood pressure, high cholesterol, fragility of various tissues, including blood vessels, skin, muscle, and bone, and psychological disturbances such as depression, anxiety, and insomnia.3 Untreated, the five-year survival rate is only approximately 50%.4 About Recorlev® Recorlev® (levoketoconazole) is a cortisol synthesis inhibitor for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.1 Endogenous Cushing’s syndrome is a rare but serious and potentially fatal endocrine disease caused by chronic elevated cortisol exposure.2 Recorlev is the pure 2S,4R enantiomer of ketoconazole, a steroidogenesis inhibitor.1 Recorlev has demonstrated in two successful Phase 3 studies to significantly reduce mean urinary free cortisol.1 The Phase 3 program for Recorlev included LOGICS and SONICS, two multinational studies designed to evaluate the safety and efficacy of Recorlev when used to treat endogenous Cushing’s syndrome. LOGICS, a double-blind, placebo-controlled, randomized-withdrawal study met its key endpoint of normalizing and maintaining therapeutic response compared with placebo.1 The supportive SONICS study met its primary and secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase.1,2 The ongoing open-label OPTICS study will gather further useful information related to the long-term use of Recorlev. Recorlev received orphan drug designation from the FDA and the European Medicines Agency for the treatment of endogenous Cushing's syndrome. Indication & Important Safety Information for Recorlev® BOXED WARNING: HEPATOTOXICITY AND QT PROLONGATION HEPATOTOXICITY Cases of hepatotoxicity with fatal outcome or requiring liver transplantation have been reported with oral ketoconazole. Some patients had no obvious risk factors for liver disease. Recorlev is associated with serious hepatotoxicity. Evaluate liver enzymes prior to and during treatment. QT PROLONGATION Recorlev is associated with dose-related QT interval prolongation. QT interval prolongation may result in life-threatening ventricular dysrhythmias such as torsades de pointes. Perform ECG and correct hypokalemia and hypomagnesemia prior to and during treatment. INDICATION Recorlev is a cortisol synthesis inhibitor indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Limitations of Use Recorlev is not approved for the treatment of fungal infections. CONTRAINDICATIONS Cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT > 3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease. Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes. Prolonged QTcF interval > 470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or prolonged QT syndrome. Known hypersensitivity to levoketoconazole, ketoconazole or any excipient in Recorlev. Taking certain drugs that are sensitive substrates of CYP3A4 or CYP3A4 and P-gp. WARNINGS AND PRECAUTIONS Hepatotoxicity Serious hepatotoxicity has been reported in patients receiving Recorlev, irrespective of the dosages used or the treatment duration. Drug-induced liver injury (peak ALT or AST greater than 3 times upper limit of normal) occurred in patients using Recorlev. Avoid concomitant use of Recorlev with hepatotoxic drugs. Advise patient to avoid excessive alcohol consumption while on treatment with Recorlev. Routinely monitor liver enzymes and bilirubin during treatment. QT Prolongation Use Recorlev with caution in patients with other risk factors for QT prolongation, such as congestive heart failure, bradyarrhythmias, and uncorrected electrolyte abnormalities, with more frequent ECG monitoring considered. Routinely monitor ECG and blood potassium and magnesium levels during treatment. Hypocortisolism Recorlev lowers cortisol levels and may lead to hypocortisolism with a potential for life-threatening adrenal insufficiency. Lowering of cortisol levels can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significant lowering of serum cortisol levels may result in adrenal insufficiency that can be manifested by hypotension, abnormal electrolyte levels, and hypoglycemia. Routinely monitor 24-hour urine free cortisol, morning serum or plasma cortisol, and patient’s signs and symptoms for hypocortisolism during treatment. Hypersensitivity Reactions Hypersensitivity to Recorlev has been reported. Anaphylaxis and other hypersensitivity reactions including urticaria have been reported with oral ketoconazole. Risks Related to Decreased Testosterone Recorlev may lower serum testosterone in men and women. Potential clinical manifestations of decreased testosterone concentrations in men may include gynecomastia, impotence, and oligospermia. Potential clinical manifestations of decreased testosterone concentrations in women include decreased libido and mood changes. ADVERSE REACTIONS Most common adverse reactions (incidence > 20%) are nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema. DRUG INTERACTIONS Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating Recorlev.Sensitive CYP3A4 or CYP3A4 and P-gp Substrates: Concomitant use of Recorlev with these substrates is contraindicated or not recommended.Atorvastatin: Use lowest atorvastatin dose possible and monitor for adverse reactions for dosages exceeding 20 mg daily.Metformin: Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed.Strong CYP3A4 Inhibitors or Inducers: Avoid use of these drugs 2 weeks before and during Recorlev treatment.Gastric Acid Modulators: See Full Prescribing Information for recommendations regarding concomitant use with Recorlev. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed during treatment and for one day after final dose. To report SUSPECTED ADVERSE REACTIONS, contact Xeris Pharmaceuticals, Inc. at 1-877-937-4737 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see Full Prescribing Information, including Boxed Warning. About Xeris Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical company committed to improving patients’ lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, Keveyis®, the first FDA-approved therapy for primary periodic paralysis, and Recorlev® for the treatment of endogenous Cushing’s syndrome. Xeris also has an increasingly diverse pipeline of development and partnered programs using its proprietary formulation technology platforms, XeriSol™ and XeriJect™, bringing new products forward for the company as well as its partners Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit www.xerispharma.com, or follow us on Twitter, LinkedIn, or Instagram.

Acquisition to access global rights to baxdrostat, a novel aldosterone synthase inhibitor in development for blood pressure lowering LONDON, UK I January 09, 2023 I AstraZeneca has entered into a definitive agreement to acquire CinCor Pharma, Inc. (CinCor), a US-based clinical-stage biopharmaceutical company, focused on developing novel treatments for resistant and uncontrolled hypertension as well as chronic kidney disease. The acquisition will bolster AstraZeneca’s cardiorenal pipeline by adding CinCor’s candidate drug, baxdrostat (CIN-107), an aldosterone synthase inhibitor (ASI) for blood pressure lowering in treatment-resistant hypertension. Baxdrostat represents a potentially leading next-generation ASI as it is highly selective for aldosterone synthase and spares the cortisol pathway in humans 1 . The opportunity also brings the potential for combination with Farxiga and complements AstraZeneca’s strategy to provide added benefit across cardiorenal diseases, where there is a high unmet medical need. Mene Pangalos, Executive Vice President BioPharmaceuticals R&D, AstraZeneca, said: “Acquiring CinCor supports our commitment to cardiorenal disease and further strengthens our pipeline with baxdrostat. Excess levels of aldosterone are associated with hypertension and several cardiorenal diseases, including chronic kidney disease and coronary artery disease and being able to effectively reduce this would offer a much-needed treatment option for these patients.” Marc de Garidel, CEO CinCor, said: “We are excited about the proposed acquisition of CinCor Pharma by AstraZeneca as we believe it offers the prospect of accelerating the development timeline and expanding the breadth of benefits patients with cardiorenal diseases might obtain from baxdrostat, if approved. CinCor is committed to ensuring a smooth transition of the development responsibilities to AstraZeneca once the acquisition is consummated. Thank you to all who have played, and will continue to play, essential roles in developing and evaluating baxdrostat as a potential novel treatment for cardiorenal diseases.” Financial considerations Under the terms of the agreement, AstraZeneca will initiate a tender offer to acquire all of CinCor’s outstanding shares for a price of $26 per share in cash at closing, plus a non-tradable contingent value right of $10 per share in cash payable upon a specified regulatory submission of a baxdrostat product. The upfront cash portion of the consideration represents a transaction value of approximately $1.3bn and a 121% premium over CinCor’s closing market price on 06 January 2023. Combined, the upfront and maximum potential contingent value payments represent, if achieved, a transaction value of approximately $1.8bn and a 206% premium over CinCor’s closing market price on 6 January 2023. As part of the transaction, AstraZeneca will acquire the cash and marketable securities on CinCor’s balance sheet, which totalled approximately $522m as of 30 September 2022. Notes Baxdrostat (CIN-107) Baxdrostat is a highly selective, oral small molecule inhibitor of aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal gland, in development for patient populations with significant unmet medical needs, including treatment-resistant hypertension, primary aldosteronism and chronic kidney disease. Baxdrostat selectively targets aldosterone synthase, which is encoded by the CYP11B2 gene while having a much lower affinity for the blocking activity of 11ß-hydroxylase, the enzyme responsible for cortisol synthesis, which is encoded by the CYP11B1 gene. In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels, across a wide range of doses 1 . In patients with treatment-resistant hypertension, a key focus area, baxdrostat met the primary endpoint in the BrigHTN Phase II trial showing a statistically significant reduction in systolic blood pressure (SBP) after a 12-week treatment period 1,2 . Baxdrostat did not meet the primary endpoint of showing a statistically significant reduction in SBP at eight weeks in the HALO Phase II trial in patients with uncontrolled hypertension 3,4 . Baxdrostat was well tolerated in both trials. Two additional Phase II trials are ongoing in hypertensive patients with primary aldosteronism (Spark-PA) 5 and in chronic kidney disease (CKD) 6 . A Phase III trial of baxdrostat is planned to start in treatment-resistant hypertension during the first half of 2023. CinCor holds the exclusive, worldwide licence to baxdrostat, which will remain in place following the transaction. Farxiga Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Farxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas 7-9 . Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and chronic kidney disease (CKD) 10-13 . Transaction details The closing of the tender offer will be subject to certain conditions, including the tender of shares representing at least a majority of the total number of CinCor’s outstanding shares, and other customary regulatory clearances. Upon the successful completion of the tender offer, AstraZeneca’s acquisition subsidiary will be merged with and into CinCor, and any remaining shares of common stock of CinCor will be cancelled and converted into the right to receive the same merger consideration (including the contingent value right) per share payable in the tender offer. Subject to the satisfaction of the conditions in the merger agreement, the acquisition is expected to close in the first quarter of 2023. Important information about the tender offer The tender offer described in this announcement has not yet commenced. This announcement is for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell any shares of the common stock of CinCor or any other securities, nor is it a substitute for the tender offer materials described herein. At the time the planned tender offer is commenced, a tender offer statement on Schedule TO, including an offer to purchase, a letter of transmittal and related documents, will be filed by AstraZeneca PLC (AstraZeneca), AstraZeneca Finance and Holdings Inc. and Cinnamon Acquisition, Inc., a wholly-owned indirect subsidiary of AstraZeneca, with the Securities and Exchange Commission (the SEC), and a solicitation/recommendation statement on Schedule 14D-9 will be filed by CinCor with the SEC. INVESTORS AND SECURITY HOLDERS ARE URGED TO CAREFULLY READ BOTH THE TENDER OFFER MATERIALS (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND CERTAIN OTHER TENDER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT ON SCHEDULE 14D-9 REGARDING THE OFFER, AS THEY MAY BE AMENDED FROM TIME TO TIME, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT INVESTORS AND SECURITY HOLDERS SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SECURITIES. Investors and security holders may obtain a free copy of the Offer to Purchase, the related Letter of Transmittal, certain other tender offer documents and the Solicitation/Recommendation Statement (when available) and other documents filed with the SEC at the website maintained by the SEC at www.sec.gov or by directing such requests to the information agent for the tender offer, which will be named in the tender offer statement. In addition, CinCor files annual, quarterly and current reports and other information, and AstraZeneca files annual reports and other information with the SEC, which are available to the public from commercial document-retrieval services and at the SEC’s website at www.sec.gov . Copies of the documents filed with the SEC by AstraZeneca may be obtained at no charge on the investor relations page of AstraZeneca’s internet website at www.astrazeneca.com /investors. Copies of the documents filed with the SEC by CinCor may be obtained at no charge under the “Investors” section of CinCor’s internet website at www.cincor.com . Forward-looking statements This announcement may include statements that are not statements of historical fact, or “forward-looking statements,” including with respect to AstraZeneca’s proposed acquisition of CinCor. Such forward-looking statements include, but are not limited to, the ability of AstraZeneca and CinCor to complete the transactions contemplated by the acquisition agreement, including the parties’ ability to satisfy the conditions to the consummation of the offer contemplated thereby and the other conditions set forth in the merger agreement, statements about the expected timetable for completing the transaction, AstraZeneca’s and CinCor’s beliefs and expectations and statements about the benefits sought to be achieved in AstraZeneca’s proposed acquisition of CinCor, the potential effects of the acquisition on both AstraZeneca and CinCor, the possibility of any termination of the acquisition agreement, as well as the expected benefits and success of baxdrostat and any combination product. These statements are based upon the current beliefs and expectations of AstraZeneca’s and CinCor’s management and are subject to significant risks and uncertainties. There can be no guarantees that the conditions to the closing of the proposed transaction will be satisfied on the expected timetable or at all or that baxdrostat or any combination product will receive the necessary regulatory approvals or prove to be commercially successful if approved. If underlying assumptions prove inaccurate or risks or uncertainties materialise, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, uncertainties as to the timing of the offer and the subsequent merger; uncertainties as to how many of CinCor’s stockholders will tender their shares in the offer; the risk that competing offers or acquisition proposals will be made; the possibility that various conditions to the consummation of the offer and the merger contemplated by the acquisition agreement may not be satisfied or waived; the ability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing; the effects of disruption from the transactions contemplated by the acquisition agreement and the impact of the announcement and pendency of the transactions on CinCor’s business; the risk that stockholder litigation in connection with the offer or the merger may result in significant costs of defense, indemnification and liability; the possibility that the milestone related to the contingent value right will not be achieved; general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of COVID-19; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; competition from other products; and challenges inherent in new product development, including obtaining regulatory approval. Neither AstraZeneca nor CinCor undertakes any obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in AstraZeneca’s Annual Report on Form 20-F for the year ended 31 December 2021, CinCor’s Annual Report on Form 10-K for the year ended 31 December 2021 and CinCor’s Quarterly Reports on Form 10-Q for the three months ended 31 March 2022, 30 June 2022 and 30 September 2022, in each case as amended by any subsequent filings made with the SEC. These and other filings made by AstraZeneca and CinCor with the SEC are available at the SEC’s Internet site (www.sec.gov). AstraZeneca in CVRM Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca . References 1. Freeman MW, et al. (2022) Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. NEJM , DOI: 10.1056/NEJMoa2213169. 2. A Study of CIN-107 in Adults With Treatment-Resistant Hypertension (rHTN) (BrigHTN). Available from: https://www.clinicaltrials.gov/ct2/show/NCT04519658?term=cin-107&draw=2&rank=2 [Last accessed 28 Dec 2022] 3. CinCor Pharma Announces Topline Data for Phase 2 HALO Trial Evaluating Selective Aldosterone Synthase Inhibitor Baxdrostat in Uncontrolled Hypertension. Available from: https://www.cincor.com/news-releases/news-release-details/cincor-pharma-announces-topline-data-phase-2-halo-trial [Last accessed 30 Dec 2022]. 4. A Study of CIN-107 in Patients With Uncontrolled Hypertension Receiving 1 Antihypertensive Agent (HALO). 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