Trofinetide

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the European Commission (EC) has granted marketing authorization for DAYBU (trofinetide) for the treatment of neurobehavioral symptoms of Rett syndrome in adults and pediatric patients aged five years and older, making it the first and only treatment approved for Rett syndrome in the European Union (EU). “The approval of DAYBU marks a significant milestone for the Rett syndrome community in the EU and advances our mission to bring this innovative treatment to patients and families who have long faced a profound unmet medical need,” said Catherine Owen Adams, Acadia’s Chief Executive Officer. “For people living with Rett syndrome, a devastating rare neurodevelopmental disorder, there have been no approved treatment options in the EU. We are proud to make DAYBU available and look forward to supporting patients, caregivers, and healthcare providers gain access to treatment." The DAYBU marketing authorization in the EU is primarily based on results from the Phase 3 LAVENDER™ study, which demonstrated statistically significant and clinically meaningful improvements in core features of Rett syndrome, as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scale co-primary endpoints. “Rett syndrome places a profound burden on individuals, families, and caregivers, yet treatment options have remained extremely limited,” said Prof. Nadia Bahi, MD, PhD, Pediatric Neurology at Necker-Enfants Malades University Hospital, Paris Cité University, Paris, France. “Today's approval in the European Union is an important milestone that recognizes the significant unmet medical need in this rare disease. It provides clinicians with a new treatment option to help address the neurobehavioral symptoms of Rett syndrome and represents progress for the Rett community.” With this approval, DAYBU is authorized to be marketed in all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. As a next step, Acadia will now begin pricing and reimbursement negotiations with relevant national authorities to potentially bring DAYBU to patients across the EU. About Rett Syndrome Rett syndrome is a rare, complex, neurodevelopmental disorder and occurs in approximately one of every 10,000 to 15,000 female births worldwide. 1-3 A child with Rett syndrome generally exhibits an early period of apparently normal development until six to 18 months, when many of their skills seem to slow down or stagnate. This is typically followed by a regression phase when the child loses acquired communication skills and purposeful hand use. The child may then experience a plateau period in which they could show mild recovery in cognitive interests, but body movements remain severely diminished. As they age, those individuals living with Rett may continue to experience a stage of motor deterioration, which can last the rest of the patient’s life. 2 Rett syndrome is typically caused by a genetic mutation on the MECP2 gene. 4 In preclinical studies, deficiency in MeCP2 function is thought to lead to impairment in synaptic communication and brain plasticity, and the deficits in synaptic function may be associated with Rett manifestations. 4-6 Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities. 7 Most individuals living with Rett syndrome typically live into adulthood and require intense round-the-clock care. 1,8 Rett syndrome is associated with a substantial physical, psychological, social, and economic burden, significantly affecting the quality of life of both patients and their caregivers. 9-11 About DAYBU ® (trofinetide) In Rett syndrome, levels of insulin-like growth factor 1 (IGF-1) in the brain are lower than normal, which is thought to affect nerve function. IGF-1 is a hormone that is important for the normal development and functioning of the nervous system. The active substance in DAYBU (trofinetide), is made up of a molecule derived from IGF-1. Trofinetide is approved for use under the name DAYBUE ® and DAYBUE ® STIX in the United States and under the name DAYBUE ® in Canada and DAYBU ® in the European Union. About Acadia Pharmaceuticals Acadia is committed to turning scientific promise into meaningful innovation that makes the difference for underserved neurological and rare disease communities around the world. Our commercial portfolio includes the first and only FDA-approved treatments for Parkinson’s disease psychosis and Rett syndrome. We are developing the next wave of therapeutic advancements with a robust and diverse pipeline that includes mid- to late-stage programs in Alzheimer’s disease psychosis and Lewy body dementia psychosis, along with earlier-stage programs that address other underserved patient needs. At Acadia, we’re here to be their difference. For more information, visit us at acadia.com and follow us on LinkedIn and X . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “potential,” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the importance of DAYBU as a treatment for neurobehavioral symptoms of Rett syndrome in adults and pediatric patients aged five years and older, the anticipated benefits of DAYBU to patients, caregivers, healthcare providers, and the Rett community, the clinical benefit of DAYBU, the ability of patients to gain access to DAYBU, and our expectations regarding the future occurrence of pricing and reimbursement negotiations, including our ability to timely gain pricing and reimbursement of DAYBU ® in EU member states, Iceland, Liechtenstein, and Norway. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties and other factors include, but are not limited to, the inherent uncertainty regarding the pricing and reimbursement negotiations; our dependency on the continued successful commercialization of our products and our ability to maintain or increase sales of our products; our ability to obtain necessary regulatory approvals to commercialize our products and product candidates; if and when approved, market acceptance of our products and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties and other factors that may cause our actual results, performance or achievements to differ, please refer to our quarterly report on Form 10-Q for the period ended June 30, 2026, filed on August 5, 2026, as well as our subsequent filings with the Securities and Exchange Commission from time to time. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law. References 1 Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open . 2020;4:e000717. 2 Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018; 8:170216. 3 May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J Med Econ . 2023;26(1):1570-1580. 4 Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2):185-188. 5 Fukuda T, Itoh M, Ichikawa T, et al. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005; 64(6):537-544. 6 Asaka Y, Jugloff DG, Zhang L, et al. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis . 2006; 21(1):217-227. 7 Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol . 2010; 68(6):944-950. 8 Tarquinio DO, Hou W, Neul JL, et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015; 53(5):402-411. 9 Prange EO, Beisang A, Pehlivan D, et al. Expert Consensus on Real-World Use of Trofinetide for Rett Syndrome Using a Modified Delphi Method. Annals of the Child Neurology Society . 2026; 38–51. 10 Kaufmann WE, Percy AK, Neul JL, et al. Burden of illness in Rett syndrome: initial evaluation of a disorder-specific caregiver survey. Orphanet J Rare Dis . 2024;19(1):296. 11 Gold WA, Percy AK, Neul JL, et al. Rett syndrome. Nat Rev Dis Primers . 2024;10(1):84. Contacts Investor Contact: Acadia Pharmaceuticals Inc. Al Kildani (858) 261-2872 ir@acadia-pharm.com Acadia Pharmaceuticals Inc. Jessica Tieszen (858) 261-2950 ir@acadia-pharm.com Media Contact: Acadia Pharmaceuticals Inc. Deb Kazenelson (818) 395-3043 media@acadia-pharm.com

- Second quarter DAYBUE ® GAAP net sales of $125 million, up 30% year-over-year driven by strong uptake of DAYBUE STIX - Second quarter NUPLAZID ® GAAP net sales of $183 million, up 10% year-over-year on a non-GAAP adjusted basis - Increased full year 2026 total revenue guidance to $1.24 to $1.30 billion, reflecting higher DAYBUE guidance of $480 to $510 million and reaffirmed NUPLAZID guidance of $760 to $790 million - Topline results from the Phase 2 remlifanserin study in Alzheimer’s disease psychosis anticipated September to October 2026 ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD), today announced its financial results for the second quarter ended June 30, 2026. “Acadia delivered an outstanding second quarter, highlighted by strong commercial execution across both DAYBUE and NUPLAZID, resulting in total revenue growth of 17% year-over-year on an adjusted basis,” said Catherine Owen Adams, Chief Executive Officer of Acadia. “For DAYBUE, continued patient demand and robust uptake of STIX drove another quarter of strong performance. For NUPLAZID, we continued to see strong momentum, especially in new-to-brand prescriptions as our recently expanded sales force gained traction in the field. We remain confident that both franchises are on track to achieve our long-term ambition of approximately $1.7 billion in annual net sales in 2028. Looking ahead, we are excited about the anticipated topline results from our Phase 2 program evaluating remlifanserin in Alzheimer's disease psychosis in the September to October timeframe, which we believe represents a potentially transformational opportunity for Acadia.” Company Updates Completed enrollment in the Phase 2 portion of the RADIANT program evaluating remlifanserin in Alzheimer's disease psychosis and initiated Phase 3 screening and enrollment; topline Phase 2 results are expected in September to October 2026. Received FDA Fast Track designation for remlifanserin for the treatment of hallucinations and delusions associated with Alzheimer's disease psychosis, recognizing its potential to address a significant unmet medical need. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending marketing authorization for DAYBU ® (trofinetide) for the treatment of neurobehavioral symptoms of Rett syndrome in adults and pediatric patients aged five years and older. If approved by the European Commission, DAYBU would become the first authorized treatment for Rett syndrome in the European Union. Financial Results Revenues GAAP total revenues, comprised of net product sales from NUPLAZID and DAYBUE, were $308 million for the second quarter of 2026, up 16% as compared to GAAP total revenues of $265 million in the second quarter of 2025, and up 17% as compared to non-GAAP adjusted total revenues of $262 million in the second quarter of 2025. GAAP net product sales of NUPLAZID were $183 million for the second quarter of 2026, up 9% compared to GAAP net product sales of $168 million for the second quarter of 2025, and up 10% as compared to non-GAAP adjusted net product sales of $166 million for the second quarter of 2025. Net product sales of DAYBUE were $125 million for the second quarter of 2026, an increase of 30% as compared to $96 million for the second quarter of 2025. A reconciliation of NUPLAZID non-GAAP adjusted net product sales and non-GAAP adjusted total revenues is provided in Table 1. A description of these adjustments is included under ‘Non-GAAP Financial Measures.’ Research and Development Research and development expenses for the second quarter of 2026 were $82 million, compared to $78 million for the same period of 2025. Selling, General and Administrative Selling, general and administrative expenses for the second quarter of 2026 were $160 million, compared to $134 million for the same period of 2025. Net Income For the second quarter of 2026, Acadia reported net income of $32 million, or $0.18 per diluted share, compared to a net income of $27 million, or $0.16 per diluted share, for the same period in 2025. Cash and Investments At June 30, 2026, Acadia’s cash, cash equivalents, and investment securities totaled $956 million, compared to $820 million at December 31, 2025. Full Year 2026 Financial Guidance (GAAP): Acadia is updating its 2026 guidance: Total revenues revised to a range of $1.24 to $1.30 billion, up from the previous range of $1.22 to $1.28 billion. NUPLAZID net product sales in the range of $760 to $790 million. DAYBUE (including all forms of trofinetide) global net product sales in the range of $480 to $510 million, up from the previous range of $460 to $490 million. R&D expense in the range of $355 to $380 million, down from the previous range of $385 to $410 million. SG&A expense in the range of $660 to $700 million. Conference Call and Webcast Information Acadia will host a conference call to discuss the second quarter 2026 results today, Tuesday, August 4, 2026 at 1:30 p.m. PT/4:30 p.m. ET. The conference call may be accessed by registering for the call here . Once registered, participants will receive an email with the dial-in number and unique PIN number to use for accessing the call. About NUPLAZID ® (pimavanserin) Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID. About DAYBUE ® (trofinetide) Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. Trofinetide was approved for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older by the U.S. Food and Drug Administration in March 2023 under the trade name DAYBUE or DAYBUE STIX. About Acadia Pharmaceuticals Acadia is committed to turning scientific promise into meaningful innovation that makes the difference for underserved neurological and rare disease communities around the world. Our commercial portfolio includes the first and only FDA-approved treatments for Parkinson’s disease psychosis and Rett syndrome. We are developing the next wave of therapeutic advancements with a robust and diverse pipeline that includes mid- to late-stage programs in Alzheimer’s disease psychosis and Lewy body dementia psychosis, along with earlier-stage programs that address other underserved patient needs. At Acadia, we’re here to be their difference. For more information, visit us at acadia.com and follow us on LinkedIn and X . Non-GAAP Financial Measures This press release contains the following financial measures that do not comply with U.S. generally accepted accounting principles (GAAP): non-GAAP adjusted net product sales for NUPLAZID for the second quarter of 2025 and non-GAAP adjusted total revenues for the second quarter of 2025. In preparing these non-GAAP financial results, the Company includes adjustments made to reflect the impact of a change in estimate related to NUPLAZID IRA rebate accruals. Please refer to our press release dated February 25, 2026, for additional details. These non-GAAP financial measures complement GAAP results and are used by management to analyze financial performance and evaluate period-to-period changes. Management believes these non-GAAP financial measures are useful to investors and other users of the Company’s financial statements to facilitate period-to-period comparability. These non-GAAP financial measures are not meant to be considered as a substitute for comparable GAAP measures; should be read in conjunction with the Company’s consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are unlikely to be comparable with non-GAAP disclosures released by other companies. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential,” “guidance,” “continue” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release, include, but are not limited to, statements about: (i) our business strategy, objectives and opportunities, including support for and innovations in our pipeline assets and business development opportunities, sales growth for DAYBUE and uptake in DAYBUE STIX, and potential for enhanced shareholder value; (ii) the momentum and expectations for NUPLAZID with the expanded sales force, (iii) the FDA’s potential review of a new drug application for remlifanserin as a treatment for Alzheimer’s disease psychosis, (iv) the receipt and timing of the topline results of the RADIANT Phase 2 study, the transformational opportunity of those results, and the enrollment of the Phase 3 portion of the RADIANT development program, (v) potential approval of DAYBU (trofinetide) in the European Union, (vi) plans for, including timing, development and progress of commercialization or regulatory timelines for our products and our product candidates; (vii) benefits to be derived from and efficacy of our products, including the potential advantages of our products; and (viii) our estimates regarding our future financial performance, profitability, capital requirements or expenses, including our full year 2026 financial guidance and anticipated net product sales by the end of 2028. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties and other factors include, but are not limited to: our dependency on the continued successful commercialization of our products and our ability to maintain or increase sales of our products; the success of our plans to continue commercial growth; the costs of our commercialization plans and development programs, and the financial impact or revenues from any commercialization we undertake; our ability to obtain necessary regulatory approvals for our product candidates and, if and when approved, market acceptance of our products; the risks associated with clinical trials and their outcomes, including risks of unsuccessful enrollment and negative or inconsistent results; our dependence on third-party collaborators, clinical research organizations, manufacturers, suppliers and distributors; the impact of competitive products and therapies; our ability to generate or obtain the necessary capital to fund our operations; our ability to grow, equip and train our specialized sales forces; our ability to manage the growth and complexity of our organization; our ability to maintain, protect and enhance our intellectual property; and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties and other factors that may cause our actual results, performance or achievements to differ, please refer to our annual report on Form 10-K for the year ended December 31, 2025 as well as our subsequent filings with the Securities and Exchange Commission from time to time. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law. ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except per share amounts) (Unaudited) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Revenues Product sales, net $ 307,959 $ 264,566 $ 576,021 $ 508,882 Total revenues 307,959 264,566 576,021 508,882 Operating expenses Cost of product sales (1)(2) 28,316 20,734 53,107 41,126 Research and development (2) 81,555 77,951 158,423 156,216 Selling, general and administrative (2) 160,252 133,507 331,271 259,877 Total operating expenses 270,123 232,192 542,801 457,219 (Loss) income from operations 37,836 32,374 33,220 51,663 Interest income, net 7,990 7,243 16,045 15,144 Other income 647 594 1,189 1,183 Income before income taxes 46,473 40,211 50,454 67,990 Income tax expense 14,973 13,545 15,317 22,337 Net income $ 31,500 $ 26,666 $ 35,137 $ 45,653 Earnings per share: Basic $ 0.18 $ 0.16 $ 0.21 $ 0.27 Diluted $ 0.18 $ 0.16 $ 0.20 $ 0.27 Weighted average common shares outstanding: Basic 171,603 167,827 171,063 167,321 Diluted 172,851 168,681 172,890 168,219 (1) Includes license fees and royalties (2) Includes the following stock-based compensation expense Cost of product sales $ 510 $ 18 $ 838 $ 352 Research and development $ 4,746 $ 4,477 $ 8,888 $ 7,910 Selling, general and administrative $ 11,684 $ 9,845 $ 21,912 $ 17,458 ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) (Unaudited) June 30, 2026 December 31, 2025 (unaudited) Assets Cash, cash equivalents and investment securities $ 956,474 $ 819,686 Accounts receivable, net 150,642 121,457 Interest and other receivables 15,688 26,774 Inventory 32,372 34,670 Prepaid expenses and other current assets 69,369 59,526 Total current assets 1,224,545 1,062,113 Property and equipment, net 17,107 7,511 Operating lease right-of-use assets 69,424 47,354 Intangible assets, net 103,448 108,893 Restricted cash 7,846 7,845 Long-term inventory 76,301 76,704 Deferred tax assets 240,679 249,879 Other assets 3,550 3,896 Total assets $ 1,742,900 $ 1,564,195 Liabilities and stockholders’ equity Accounts payable $ 44,566 $ 10,903 Accrued liabilities 316,870 266,211 Total current liabilities 361,436 277,114 Operating lease liabilities 59,547 40,554 Other long-term liabilities 15,308 19,137 Total liabilities 436,291 336,805 Total stockholders’ equity 1,306,609 1,227,390 Total liabilities and stockholders’ equity $ 1,742,900 $ 1,564,195 Table 1. ACADIA PHARMACEUTICALS INC. NON-GAAP RECONCILIATION (in millions) (Unaudited) 2Q25 2Q26 GAAP NUPLAZID Net Sales $ 168.5 $ 183.2 Allocation of 2025 Amount $ (2.4 ) $ — Non-GAAP Adjusted NUPLAZID Net Sales $ 166.1 $ 183.2 DAYBUE products Net Sales $ 96.1 $ 124.8 Non-GAAP Adjusted Total Revenues $ 262.2 $ 308.0 Contacts Investor Contact: Acadia Pharmaceuticals Inc. Al Kildani (858) 261-2872 ir@acadia-pharm.com Acadia Pharmaceuticals Inc. Jessica Tieszen (858) 261-2950 ir@acadia-pharm.com Media Contact: Acadia Pharmaceuticals Inc. Deb Kazenelson (818) 395-3043 media@acadia-pharm.com