Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency

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

- Increase in endogenous cortisol production achieved in all patients in higher dose cohorts of BBP-631, a result seen for the first time ever in CAH patients - The gene therapy was well tolerated with no treatment-related serious adverse events (SAEs) reported - Despite novel scientific advancements achieved with this program, the data do not warrant additional capital investment at this time and the gene therapy budget is being significantly reduced PALO ALTO, Calif., Sept. 10, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases, today announced topline results from the Phase 1/2 open-label ADventure study investigating BBP-631, the Company’s investigational adeno-associated virus (AAV) 5 gene therapy, for the treatment of congenital adrenal hyperplasia (CAH). The Phase 1/2 open-label ADventure study was designed to evaluate the safety, tolerability and pharmacodynamic activity of BBP-631 in adults with classic CAH. To date, key results from the study include: Increased endogenous cortisol production was achieved in all patients at higher doses. A maximum change from baseline post-ACTH stimulation test of 4.7 μg/dL and 6.6 μg/dL was observed at the two highest dose levels, respectively, with cortisol levels as high as 11 μg/dL achieved. Substantial and durable increases in 11-deoxycortisol, the product of 21-hydroxylase, and reductions in 17-hydroxyprogesterone (17-OHP), the substrate of 21-hydroxylase, provide compelling evidence of durable BBP-631 transgene activity. At the highest dose levels, sustained 11-deoxycortisol averaged a 55-fold increase from baseline with a maximum of 99-fold increase from baseline. These represent an average maximum of 23-fold the upper-limit of normal. Robust reduction in 17-hydroxyprogesterone, with the majority of patients reaching a reduction of ≥50%, with a max reduction of 95%. BBP-631 has been well tolerated with only mild to moderate treatment-emergent adverse events (TEAEs) and no treatment-related SAEs reported. “While the data to date are not yet transformational, the study showed for the first time that people living with CAH can indeed make their own cortisol, and that gene therapy can be safely administered in this patient population. We remain committed to finding the right partner for those in the CAH community and are grateful to the participants and those who expressed interest in both the pre-screening study and the ADventure study. We also want to thank the ADventure study investigators and staff, the CAH patient advocacy organizations and the broader CAH community,” said Neil Kumar, Ph.D., CEO and Founder of BridgeBio. “Given that the results of the trial did not meet the threshold to warrant additional capital investment at this time, BridgeBio will be reducing the gene therapy budget more than $50M, consistent with our capital allocation principles, and reserving gene therapy for priority targets that we cannot treat any other way,” said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. “We believe that gene therapies have the potential to fulfill a significant unmet need and are eager to work closely with the FDA and the Canavan community with the goal of bringing our therapy to families living with Canavan disease as fast as possible.” BridgeBio will no longer be pursuing development of BBP-631 for CAH and the Company is actively seeking partnership opportunities to support future development of BBP-631 or next-generation gene therapies for the treatment of CAH, a very prevalent genetic disease that still has significant unmet need, with more than 75,000 cases estimated in the United States and European Union. About BBP-631 BBP-631 is an AAV5 gene therapy developed to treat CAH due to 21-hydroxylase deficiency at its source. BBP-631 is designed to deliver a functional copy of the 21-hydroxylase gene and has been shown through multiple preclinical studies to result in efficient and persistent delivery to the adrenal gland, where hormones are naturally made. If successful, BBP-631 may restore the body’s hormone and steroid balance by enabling people with CAH to naturally make their own cortisol and aldosterone. It could also allow for people with CAH to eliminate or significantly reduce their daily glucocorticoid or mineralocorticoid doses, which is the current standard of care for patients. About Congenital Adrenal Hyperplasia (CAH) Affecting approximately 75,000 people in the United States and European Union, CAH is a group of genetic disorders that affect the adrenal glands, which is caused by a mutation in the gene encoding for 21-hydroxylase, an enzyme essential for making the hormones cortisol and aldosterone which are critical for various physiologic functions. Cortisol is necessary for the body to respond to injury, stress or illness, and aldosterone is required to maintain proper blood pressure and sodium levels. Unable to produce cortisol and aldosterone, people with classic CAH cannot mount the healthy physiological response to stressors, such as illnesses, that allows their heart, lungs, kidneys and other organs to compensate for the stress, which can be life-threatening. These adrenal crises can be particularly dangerous for young children. About BridgeBio Pharma, Inc. BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn , Twitter and Facebook . BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements BridgeBio makes in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “seeks,” “should,” “will,” and variations of such words or similar expressions. BridgeBio intends these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements in Dr. Kumar’s quote relating to the expectations, plans and prospects regarding BBP-631, the statements in Dr. Stephenson’s quote relating to the Company’s financial performance, capitalization status, strategy, business plans and goals and the potential for gene therapy and future partnership opportunities for BBP-631, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although BridgeBio believes that its plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, BridgeBio can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, risks inherent in developing therapeutic products, the success, cost, and timing of the Company’s product candidate research and development activities and ongoing and planned preclinical studies and clinical trials, the success and timing of preclinical study and clinical trial results, the success of its clinical trial designs, the fact that successful preliminary preclinical study or clinical trial results may not result in future clinical trial successes and/or product approvals, trends in the industry, the legal and regulatory framework for the industry, the accuracy of the Company’s estimates regarding expenses, future revenue, future expenditures and needs for and ability to obtain additional financing, the Company’s ability to be a sustainable genetic medicine innovation engine and to build the next great genetic medicine company, the Company’s ability to obtain and maintain intellectual property protection for its product candidates and approved products, the competitive environment and clinical and therapeutic potential of the Company’s product candidates and FDA-approved products, potential adverse impacts due to global health emergencies, including delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine and in Israel and the Gaza Strip, increasing rates of inflation and rising interest rates, on our business operations and expectations as well as those risks set forth in the Risk Factors section of BridgeBio’s most recent Annual Report on Form 10-K, and BridgeBio’s other filings with the U.S. Securities and Exchange Commission. Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio’s management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact: Vikram Bali contact@bridgebio.com (650)-789-8220

INGREZZA® (valbenazine) Second Quarter Net Product Sales of $580 Million Representing 32% Year-Over-Year Growth INGREZZA ® (valbenazine) 2024 Net Product Sales Guidance Raised to $2.25 - $2.3 Billion Top-Line Phase 2 Data Readouts for NBI-'568 and Luvadaxistat Remain On Track in Q3 SAN DIEGO, Aug. 1, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced its financial results for the second quarter ended June 30, 2024 and provided an update on its 2024 financial guidance. "At Neurocrine, we are energized by the tremendous opportunity we see to help many more patients, and we are encouraged by our recent progress, including INGREZZA's continued success in treating tardive dyskinesia and Huntington's disease chorea and the FDA's decision to grant Priority Review for crinecerfont to treat congenital adrenal hyperplasia," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "We are in the process of building our endocrinology team and expanding the INGREZZA salesforce, positioning our company for continued strong growth in the years ahead." Kevin Gorman added, "As I look ahead to my planned retirement in October, I have never been more confident in Neurocrine's future. I am incredibly proud of all that we have achieved together and excited to see what this team will continue to accomplish for patients under Kyle Gano's leadership." Financial Highlights INGREZZA Net Product Sales Highlights INGREZZA second quarter 2024 net product sales were $580 million and grew 32% compared to the second quarter 2023 Year-over-year growth driven by strong underlying patient demand and improvement in gross-to-net dynamics Other Key Financial Highlights Differences in second quarter 2024 GAAP and Non-GAAP operating expenses compared with second quarter 2023 were driven by: Increased R&D expense in support of an expanded and advancing clinical portfolio including investments in muscarinic compounds, gene therapy programs and second generation VMAT2 inhibitors. R&D expense for the second quarter 2024 includes $27 million for development milestones achieved under our collaborations with Nxera Pharma UK Limited (Nxera, formerly known as Sosei Heptares), Takeda Pharmaceutical Company Limited (Takeda) and Voyager Therapeutics, Inc. (Voyager) Increased SG&A expense includes incremental investment in crinecerfont-related headcount, crinecerfont-related pre-launch activities, and continued investment in INGREZZA. GAAP SG&A expense also includes impairment charges of $14 million associated with leased office space that has been vacated as we continue to occupy our new campus facility Second quarter 2024 GAAP net income and earnings per share were $65 million and $0.63, respectively, compared with $96 million and $0.95, respectively, for second quarter 2023 Second quarter 2024 Non-GAAP net income and earnings per share were $169 million and $1.63, respectively, compared with $126 million and $1.25, respectively, for second quarter 2023 Differences in second quarter 2024 GAAP and Non-GAAP net income compared with second quarter 2023 driven by: Higher INGREZZA net sales and improved operating margin Second quarter 2024 includes $50 million charge associated with the settlement of convertible senior notes conversions (Non-GAAP adjustment) Second quarter 2024 includes $20 million loss from changes in fair value of equity security investments compared to $37 million gain the second quarter 2023 (Non-GAAP adjustment) Second quarter 2024 includes $27 million of development milestones expense achieved under collaborations Second quarter 2024 includes $14 million leased office space impairment charge (Non-GAAP adjustment) At June 30, 2024, the Company had cash, cash equivalents and marketable securities totaling approximately $1.7 billion which reflects the $309 million payment to fully retire our convertible senior notes A reconciliation of GAAP to Non-GAAP financial results can be found in Table 3 and Table 4 at the end of this news release. Recent Developments Announced Kevin Gorman, Ph.D., will retire as Chief Executive Officer on October 11, 2024. Kyle Gano, Ph.D., currently Neurocrine's Chief Business Development and Strategy Officer, will succeed him in the CEO role. Dr. Gano will also join the Company's Board of Directors at that time, and Dr. Gorman will continue to serve on the Company's Board. Announced positive topline data for the Phase 2 SAVITRI™ study. This randomized, double-blind, placebo-controlled dose-finding study assessed the efficacy and safety of NBI-1065845 in adult subjects with major depressive disorder (MDD). NBI-1065845 is an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development as a potential treatment for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression. Announced FDA accepted New Drug Applications (NDAs) and granted Priority Review for crinecerfont for adult and pediatric patients with congenital adrenal hyperplasia (CAH). The agency set Prescription Drug User Fee (PDUFA) target actions dates of December 29, 2024 for the capsule formulation and December 30, 2024 for the oral solution formulation. At the Endocrine Society Annual Meeting (ENDO 2024), presented new Phase 3 clinical study data from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In parallel, announced that the primary study results from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have been published in The New England Journal of Medicine. Initiated Phase 2 study of NBI-1070770 in adults with major depressive disorder. NBI-1070770 is a novel, selective and orally active, negative allosteric modulator (NAM) of the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor. Initiated Phase 1 study of NBI-1117567 in healthy adult participants. NBI-1117567 is an investigational, oral, M1/M4 (M1 preferring) selective muscarinic agonist for the potential treatment of neurological and neuropsychiatric conditions. Initiated Phase 1 study of NBI-1076968 in healthy adult participants. NBI-1076968 is an investigational, oral, M4 subtype-selective muscarinic antagonist for the potential treatment of movement disorders. Received notification from the Centers for Medicare and Medicaid Services that INGREZZA qualified for the Specified Small Manufacturer Exception pertaining to the Part D redesign of the Inflation Reduction Act. Settled the convertible senior notes due May 15, 2024 in full in cash upon maturity. Announced planned expansion of the INGREZZA psychiatry and long-term care sales teams to better serve patients by accelerating the number of people who are diagnosed and treated for tardive dyskinesia and chorea associated with Huntington's disease. Launched new sprinkle formulation of INGREZZA® (valbenazine) capsules for the treatment of adults with tardive dyskinesia and chorea associated with Huntington's disease. Raised 2024 Net Sales Guidance and Updated Expense Guidance 2024 Pipeline Milestones and Key Activities Key: AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; CFR1 = Corticotropin-Releasing Factor Type 1; M4 = M4 Muscarinic Receptor; DAAO = d-amino acid oxidase; NMDA NR2B NAM = n-methyl-d-aspartate Receptor Subtype 2B Negative Allosteric Modulator; VMAT2 = Vesicular Monoamine Transporter 2; M1 = M1 Muscarinic Receptor Neurocrine Biosciences Partners: * Partnered with Takeda Pharmaceutical Company Limited; ** In-Licensed from Nxera Pharma UK Limited (formerly Sosei Heptares) Conference Call and Webcast Today at 8:00 AM Eastern Time Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-445-7795 (US) or 785-424-1699 (International) using the conference ID: NBIX. The webcast and accompanying slides can also be accessed at approximately 8:00 a.m. Eastern Time on Neurocrine Biosciences' website under Investors at . A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month. About Neurocrine Biosciences Neurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine, and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (Formerly Twitter) and Facebook. (*in collaboration with AbbVie) NEUROCRINE BIOSCIENCES, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo is a trademark of Neurocrine Biosciences, Inc. Non-GAAP Financial Measures In addition to the financial results and financial guidance that are provided in accordance with accounting principles generally accepted in the United States (GAAP), this press release also contains the following Non-GAAP financial measures: Non-GAAP R&D expense, Non-GAAP SG&A expense, and Non-GAAP net income and net income per share. When preparing the Non-GAAP financial results and guidance, the Company excludes certain GAAP items that management does not consider to be normal, including recurring cash operating expenses that might not meet the definition of unusual or non-recurring items. In particular, these Non-GAAP financial measures exclude: non-cash stock-based compensation expense, charges associated with convertible senior notes, impairment charges associated with leased properties, non-cash amortization expense related to acquired intangible assets, acquisition and integration costs, changes in fair value of equity security investments, changes in foreign currency exchange rates and certain adjustments to income tax expense. These Non-GAAP financial measures are provided as a complement to results provided in accordance with GAAP as management believes these Non-GAAP financial measures help indicate underlying trends in the Company's business, are important in comparing current results with prior period results and provide additional information regarding the Company's financial position. Management also uses these Non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the Company's business and evaluate its performance. The Company provides guidance regarding combined R&D and SG&A expenses on both a GAAP and a Non-GAAP basis. A reconciliation of these GAAP financial results to Non-GAAP financial results is included in the attached financial information. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements related to: the benefits to be derived from our products and product candidates; the value our products and/or our product candidates may bring to patients; the continued success of INGREZZA; our financial and operating performance, including our future revenues, expenses, or profits; our collaborative partnerships; expected future clinical and regulatory milestones; and the timing of the initiation and/or completion of our clinical, regulatory, and other development activities and those of our collaboration partners. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: our future financial and operating performance; risks and uncertainties associated with the commercialization of INGREZZA; risks that the crinecerfont New Drug Applications (NDAs) may not obtain regulatory approval, such approval may be delayed, or may not receive the benefits associated with priority review; risks related to the development of our product candidates; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with government and third-party regulatory and/or policy efforts which may, among other things, impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products; risks associated with competition from other therapies or products, including potential generic entrants for our products; and other risks described in our periodic reports filed with the SEC, including our Quarterly Report on Form 10-Q for the quarter ended June 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than as required by law. SOURCE Neurocrine Biosciences, Inc.