ACADIA PHARMACEUTICALS INC

Acadia Pharmaceuticals Inc. is a biopharmaceutical company focused on turning scientific promise into meaningful innovation for underserved neurological and rare disease communities around the world. The company operates two core franchises: a neurological disease franchise anchored by NUPLAZID (pimavanserin), the first and only drug approved by the U.S. Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis, and a rare disease franchise anchored by DAYBUE (trofinetide), the first and only drug approved for the treatment of Rett syndrome. The company estimates that approximately 130,000 Parkinson's disease patients are treated with an atypical antipsychotic annually in the United States, and it estimates a prevalent population of 6,000 to 9,000 people in the U.S. for Rett syndrome. In the European Union, the company estimates a prevalent population of 9,000 to 12,000 Rett syndrome patients, and in Japan, a prevalent population of 1,000 to 2,000 Rett syndrome patients. The company also estimates that approximately 200,000 Lewy Body Dementia patients are being treated with antipsychotics today.

The company faces intense competition from pharmaceutical and biotechnology companies, as well as academic and research institutions. For NUPLAZID, competition comes from off-label use of various antipsychotic drugs, including the generic drugs quetiapine, clozapine, risperidone, aripiprazole, and olanzapine. For DAYBUE, competition is indirect from off-label usage of branded and generic prescription medications targeted at individual symptoms of Rett syndrome, including antiepileptics, antipsychotics, antidepressants and benzodiazepines. The company identifies several disclosed programs in development for Rett syndrome, including UCB S.A.'s planned Phase 3 clinical trial of fenfluramine, Taysha Gene Therapies' pivotal clinical trial of an AAV9 intrathecal delivered gene therapy, and Neurogene's pivotal clinical trial of its investigational adeno-associated virus gene therapy candidate NGN-401. The company states it has a stated goal of achieving $1.0 billion in NUPLAZID net sales in 2028 and believes that with an approximate 25% current market share of the 130,000 Parkinson's disease patients treated with an atypical antipsychotic annually in the United States, there is ample opportunity to grow sales.

The company generates revenue through net product sales of its two commercial products, NUPLAZID and DAYBUE. Net product sales from these two commercial products totaled $1,071.5 million ¹ for 2025, compared with $957.8 million ² for 2024. The company sells NUPLAZID to a limited number of specialty pharmacies and specialty distributors, and sells DAYBUE in the U.S. to a single wholesale distributor with specialty pharmacy service. Four customers, each based in the United States, accounted for approximately 79% of NUPLAZID product revenue and 44% of total product revenue for the year ended December 31, 2025 ³. The company also sells DAYBUE outside of the U.S. through third party distributors. The company's strategy includes distributing NUPLAZID in the U.S. and DAYBUE in the U.S. and other jurisdictions solely through a limited network of third-party specialty distributors, specialty pharmacies or other third-party partners.

NUPLAZID (pimavanserin) is a selective serotonin inverse agonist/antagonist preferentially targeting the 5-HT2A receptor, approved by the FDA in April 2016 for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. It is the only drug approved in the United States for this condition and is available in 34 mg capsule and 10 mg tablet dosage forms. Net product sales of NUPLAZID were $680.1 million ⁴ and $609.4 million ⁵ in 2025 and 2024, respectively. The company holds worldwide commercialization rights to NUPLAZID for all indications and currently holds 25 U.S. patents that relate to pimavanserin, with the composition of matter patent covering pimavanserin and salts thereof currently having an expiration date in 2030, including a patent term extension. The company also has a stated goal of achieving $1.0 billion in NUPLAZID net sales in 2028 ⁶.

DAYBUE (trofinetide) is a novel synthetic analog of the amino-terminal tripeptide of insulin-like growth factor 1 designed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and supporting synaptic function. The FDA approved DAYBUE in March 2023 for the treatment of Rett syndrome, making it the first and only drug approved for this condition. Net product sales of DAYBUE were $391.4 million ⁷ and $348.4 million ⁸ in 2025 and 2024, respectively. The company acquired an exclusive North American license to develop and commercialize trofinetide from Neuren Pharmaceuticals Limited in August 2018, and in July 2023 expanded the agreement to acquire rights to trofinetide outside of North America as well as global rights to Neuren's development candidate NNZ-2591 in Rett syndrome and Fragile X syndrome. In December 2025, the company received FDA approval for DAYBUE STIX (trofinetide) for oral solution, a dye- and preservative-free powder formulation. Health Canada granted marketing authorization of DAYBUE in October 2024, and the Ministry of Health in Israel granted marketing authorization in December 2025. The company also has a portfolio of product candidates including remlifanserin (formerly ACP-204) for Alzheimer's disease psychosis and Lewy Body Dementia Psychosis, ACP-211 for major depressive disorder, ACP-711 for essential tremor, ACP-271 for tardive dyskinesia and Huntington's disease, and ACP-2591 for Rett syndrome and Fragile X syndrome.

In November 2024, the company entered into an exclusive worldwide license agreement with Saniona A/S for the development and commercialization of ACP-711 (formerly SAN711). Under the terms, Saniona received $28 million ⁹ upfront plus potential milestone payments of up to $582 million ¹⁰, with Saniona eligible to receive tiered royalties of mid-single digits to low double digits on net sales. In September 2025, the company announced top-line results from the COMPASS PWS study, a Phase 3 study of ACP-101 for hyperphagia in Prader-Willi syndrome, which did not demonstrate a statistically significant improvement over placebo on the primary endpoint, and as a result the company does not intend to investigate ACP-101 any further. In December 2024, the company completed the sale of its Rare Pediatric Disease Priority Review Voucher for $150 million ¹¹ before fees and expenses, of which it paid Neuren one-third of the net proceeds. In January 2025, the company submitted a marketing authorization application with the European Medicines Agency for trofinetide for the treatment of Rett syndrome. In January 2026, the company was informed by the CHMP of a negative trend vote on the MAA. The company also entered into a license and collaboration with Stoke Therapeutics, Inc. in January 2022 to discover, develop and commercialize novel RNA-based medicines for SYNGAP1 syndrome.

Total revenues were $1,071.5 million ¹² for 2025, compared with $957.8 million ¹³ for 2024 and $726.4 million ¹⁴ for 2023. Net income was $391.0 million ¹⁵ for 2025, compared with $226.5 million ¹⁶ for 2024 and a net loss of $61.3 million ¹⁷ for 2023. The increase in net income in 2025 was driven by an income tax benefit of $252.1 million ¹⁸ resulting from the reversal of a valuation allowance against deferred tax assets, as the company achieved cumulative three-year profitability. Income from operations was $104.8 million ¹⁹ for 2025, compared with $230.8 million ²⁰ for 2024 and a loss from operations of $73.4 million ²¹ for 2023. The decrease in operating income in 2025 relative to 2024 was primarily due to the absence of a $146.5 million ²² gain on sale of a non-financial asset in 2024, partially offset by revenue growth. As of December 31, 2025, the company had $819.7 million ²³ in cash, cash equivalents, and investment securities, compared to $756.0 million ²⁴ at December 31, 2024.

A key growth vector is the expansion of trofinetide to markets outside the U.S. for the treatment of Rett syndrome. In the European Union, where the company estimates a prevalent population of 9,000 to 12,000 ²⁵ Rett syndrome patients, the company filed its marketing authorization application with the European Medicines Agency in January 2025. In January 2026, the company was informed by the CHMP of a negative trend vote on the MAA, and the company intends to request a re-examination of the opinion, subject to the outcome of the CHMP vote and opinion expected in February 2026. The company is preparing for a potential launch in anticipation of a potential approval in the third quarter of 2026 ²⁶. In Japan, where the company estimates a prevalent population of 1,000 to 2,000 ²⁷ Rett syndrome patients, the company is conducting a small Phase 3 study to support a future JNDA and expects to report top-line results either in the fourth quarter of 2026 or in the first quarter of 2027 ²⁸. In Canada, where the company estimates a prevalent population of 600 to 900 ²⁹ Rett syndrome patients, Health Canada granted marketing authorization in October 2024. In Israel, where the company estimates a prevalent population of about 200 ³⁰ Rett syndrome patients, the Ministry of Health granted marketing authorization in December 2025.

Another major growth vector is the advancement of late-stage product candidates. The company has ongoing Phase 2 studies of remlifanserin in Alzheimer's disease psychosis and Lewy Body Dementia Psychosis. The Phase 2 RADIANT study for ADP is expected to enroll approximately 318 ³¹ patients and evaluate remlifanserin 30 mg and 60 mg doses compared to placebo, with top-line results expected in the August to October 2026 timeframe ³². The company initiated a Phase 2 study of ACP-211 for the treatment of major depressive disorder in the fourth quarter of 2025 and expects to report top-line results sometime between the second and third quarters of 2027 ³³. For ACP-711 for essential tremor, a Phase 2 study is expected to begin in the fourth quarter of 2026 or the first quarter of 2027 ³⁴. For ACP-271 for tardive dyskinesia and Huntington's disease, a Phase 1 study is planned for the first quarter of 2026 ³⁵. The company also plans to drive growth of NUPLAZID by increasing field force size and efficiency, leveraging real world evidence, and activating consumers with direct-to-consumer campaigns, with a stated goal of achieving $1.0 billion in NUPLAZID net sales in 2028 ³⁶. For DAYBUE, the company plans to drive new patient adoption while optimizing the patient experience, with growth expected to be driven by the introduction of DAYBUE STIX powder for oral solution, launched in the first quarter of 2026 ³⁷.

The company expects cost of product sales as a percentage of total net product sales to be in the range of a mid-single digit to high single digit percentage ³⁸ subsequent to using its entire zero cost inventories of DAYBUE. The company does not expect its cost of product sales for DAYBUE to increase significantly as a percentage of net product sales in future periods as it continues to produce inventory for future sales. The company expects research and development expenses to continue to be substantial as it conducts studies pursuant to post-marketing requirements and pursues further development of remlifanserin and other early-stage product candidates. Selling, general and administrative expenses increased to $548.9 million ³⁹ for 2025 from $488.4 million ⁴⁰ for 2024, driven by costs related to the consumer activation program for NUPLAZID and the planned expansion of the DAYBUE team.

The company outsources manufacturing activities for its products and product candidates. For NUPLAZID, the active pharmaceutical ingredient is manufactured by Siegfried AG in Switzerland, and drug product is manufactured by Patheon Pharmaceuticals Inc. and Catalent Pharma Solutions LLC. For DAYBUE, the API is manufactured by Corden Pharma Bergamo S.p.A., F.I.S. Fabbrica Italiana Sintetici S.p.A., and Flamma Group S.p.A., and drug product is manufactured by Patheon and Bend Biosciences. DAYBUE STIX drug product stick packs are manufactured by Halo Pharmaceuticals, Inc. The company states it currently has sufficient API for both NUPLAZID and DAYBUE and finished products on hand to continue commercial and clinical operations as planned. The company also notes that it takes approximately two years ⁴¹ for its third-party manufacturers to produce DAYBUE API. As of December 31, 2025, the company had a total of 798 ⁴² employees, 796 ⁴³ of whom were full-time.

The company expects that its cash, cash equivalents and investment securities, as well as funds generated by anticipated sales of its products, will be sufficient to fund its planned operations through and beyond the next 12 months ⁴⁴. As of December 31, 2025, the company had $819.7 million ⁴⁵ in cash, cash equivalents, and investment securities. The company may require additional financing in the future to fund its operations, with future capital requirements depending on many factors including the costs of acquiring additional product candidates, the scope of research and development programs, and the costs of commercializing products. The company has invested a substantial portion of its available cash in money market funds, municipal bonds, and government sponsored enterprises. The company has long-term contractual obligations related to its operating leases of $58.5 million ⁴⁶ as of December 31, 2025. As of December 31, 2025, the company may be required to make milestone payments up to $3.5 billion ⁴⁷ in the aggregate, with $0.9 billion ⁴⁸ contingent upon achieving future development and regulatory milestones and $2.6 billion ⁴⁹ contingent upon achieving future commercial milestones.

The company faces structural headwinds from healthcare reform measures that may negatively impact its ability to sell products profitably. The One Big Beautiful Bill Act, signed into law on July 4, 2025, narrowed access to ACA marketplace exchange enrollment and is expected to reduce Medicaid spending and enrollment. The current administration has announced agreements with several pharmaceutical companies requiring Most-Favored-Nation pricing for prescription drugs, and has called on Congress to enact "The Great Healthcare Plan" to codify and expand Most-Favored-Nation pricing. The Medicare Drug Price Negotiation Program could subject NUPLAZID to a negotiated price, with the company believing that 2029 ⁵⁰ is the earliest year NUPLAZID could be subject to a negotiated price. The company also faces headwinds from international trade policies, including tariffs on imported pharmaceutical products, which could materially increase costs and reduce profitability. The company notes that tariff-induced cost increases may be difficult or impossible to pass through to customers until the 2027 calendar year ⁵¹ at the earliest.

The company faces execution risks related to the regulatory approval processes outside North America for trofinetide. In January 2026, the company was informed by the CHMP of the EMA of a negative trend vote on its MAA for trofinetide for the treatment of Rett syndrome. The company also faces risks related to the successful commercialization of its products, including the extent to which physicians, patients, and caregivers accept and adopt them, the scope of FDA approvals, and the availability of coverage and adequate reimbursement from third-party payors. The company notes that the label for NUPLAZID contains a "boxed" warning related to particularly important prescribing information, and there has been attention to publicly reported deaths of patients that were prescribed NUPLAZID. The company also faces risks related to its reliance on a limited network of third-party distributors and pharmacies, and the potential for delays, suspensions, or terminations in clinical trials for its product candidates.

The company's prospects are highly dependent on the successful commercialization of NUPLAZID and DAYBUE, and the inability to establish, maintain or increase sales could materially adversely affect the business. The company faces significant risk from healthcare reform measures, including the Medicare Drug Price Negotiation Program, which could subject NUPLAZID to a negotiated price as early as 2029 ⁵², and the potential implementation of Most-Favored-Nation pricing for pharmaceutical products, which could significantly reduce U.S. drug prices. The company also faces material risk from international trade policies, including tariffs on imported pharmaceutical products, which could materially increase costs and reduce profitability, with tariff-induced cost increases potentially impossible to pass through to customers until the 2027 calendar year ⁵³ at the earliest. The regulatory approval process for trofinetide outside North America is inherently unpredictable, as evidenced by the negative trend vote from the CHMP of the EMA in January 2026 on the MAA for trofinetide for the treatment of Rett syndrome. The company also faces risk from the potential for generic competition, as it is engaged in patent infringement litigation against multiple companies that have filed Abbreviated New Drug Applications seeking approval for generic versions of NUPLAZID prior to the expiration of the company's patents.

Management's message emphasizes building a strong foundation for growth with multiple innovative commercial products and product candidates that address high unmet medical needs in neurological and rare diseases. The key strategic priorities emphasized are: maximizing growth of NUPLAZID for Parkinson's disease psychosis with a stated goal of achieving $1.0 billion in NUPLAZID net sales in 2028 ⁵⁴; driving new patient adoption of DAYBUE for Rett syndrome in the United States, with growth expected from the introduction of DAYBUE STIX powder for oral solution launched in the first quarter of 2026 ⁵⁵; advancing late-stage product candidates including remlifanserin in Alzheimer's disease psychosis and Lewy Body Dementia Psychosis, with the Phase 2 RADIANT study expected to complete enrollment in the first half of 2026 ⁵⁶ and top-line results expected in the August to October 2026 timeframe ⁵⁷; expanding trofinetide to markets outside the U.S., including the EU where the company filed an MAA in January 2025 and Japan where a Phase 3 study is ongoing; and developing early-stage product candidates and pursuing business development opportunities. Management also emphasizes investing in four core strategic capabilities: precision medicine, data innovation including artificial intelligence and machine learning, globalization, and patient empowerment.