5-HT2A receptor

On January 13, Johnson & Johnson announced that it has reached a final agreement with biopharmaceutical company Intra-Cellular Therapies, which focuses on the development and commercialization of drugs for central nervous system (CNS) diseases. Under the agreement, Johnson & Johnson will acquire all outstanding shares of Intra-Cellular Therapies at a price of $132 per share, totaling approximately $14.6 billion. The core asset of Intra-Cellular Therapies includes the orally administered antipsychotic product Caplyta (lumateperone). This drug is a 5-HT2A receptor antagonist and D2 dopamine receptor modulator, originally developed by Bristol-Myers Squibb (BMS) and licensed to Intra-Cellular Therapies for global development in 2015. In December 2019, Caplyta was approved by the FDA for the treatment of schizophrenia in adults. In December 2021, the drug was also approved for the adjunctive treatment of depressive episodes associated with bipolar I or II disorder. Furthermore, Intra-Cellular Therapies submitted a new indication application for Caplyta to the FDA in December 2024 for the adjunctive treatment of major depressive disorder (MDD) and is exploring its use in pediatric indications and long-acting formulations. Through this acquisition, Johnson & Johnson will also gain access to several pipeline candidates, including ITI-1284, lenrispodun, ITI-1020, ITI-333, and ITI-1549, further strengthening its pipeline in neuroscience. With the surge in mental health crises and the aging global population, over 1 billion people worldwide (or 1 in every 8 individuals) suffer from neuropsychiatric or neurodegenerative diseases. This substantial patient market has attracted numerous pharmaceutical companies. For instance, in December 2023, Bristol-Myers Squibb acquired Karuna Therapeutics for $14 billion, gaining the potential new schizophrenia drug Cobenfy (formerly KarXT), which was approved by the FDA in 2024. In the same month, AbbVie purchased Cerevel for $8.7 billion, obtaining several promising candidates for diseases such as schizophrenia, Parkinson's disease, and mood disorders. However, AbbVie's flagship project emraclidine failed to meet its expected endpoints in two Phase II studies targeting schizophrenia, reflecting the high-risk nature of new drug development in the neuroscience field. In October 2024, AbbVie acquired Aliada for $1.4 billion, securing its main project for Alzheimer's disease treatment ALIA-1758 to bolster its neuroscience pipeline. Similarly, in October 2024, Langbo Pharmaceuticals acquired Longboard Pharmaceuticals for $2.6 billion, obtaining a new epilepsy drug Bexicaserin. Johnson & Johnson's $14.6 billion acquisition of Intra-Cellular Therapies will undoubtedly inject new vitality into the neuroscience field. In 2024, there was only one merger in the pharmaceutical industry exceeding $10 billion, but at the start of 2025, Johnson & Johnson has made the first significant acquisition. With the JPM conference underway, more merger transactions are expected to occur in the pharmaceutical industry in the coming days.

Acquisition includes CAPLYTA ® (lumateperone), the first and only U.S. FDA-approved treatment for bipolar I and II depression as an adjunctive and monotherapy; also approved for the treatment of schizophrenia in adults sNDA submitted to U.S. FDA for CAPLYTA ® as adjunctive treatment for major depressive disorder; if approved, CAPLYTA ® has potential to become a standard of care for most common depressive disorders CAPLYTA ® adds to Johnson & Johnson’s robust lineup of therapies with $5 billion+ potential in peak year sales i and further solidifies sales growth above analyst expectations now through the remainder of the decade Promising clinical-stage pipeline with best-in-disease potential in generalized anxiety disorder and Alzheimer’s disease-related psychosis and agitation NEW BRUNSWICK, NJ & BEDMINSTER, NJ, USA I January 13, 2025 I Johnson & Johnson (NYSE: JNJ) and Intra-Cellular Therapies, Inc. (Nasdaq: ITCI) announced today that they have entered into a definitive agreement under which Johnson & Johnson will acquire all outstanding shares of Intra-Cellular Therapies, a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, for $132.00 per share in cash for a total equity value of approximately $14.6 billion. “Building on our nearly 70-year legacy in neuroscience, this unique opportunity to add Intra-Cellular Therapies to our Innovative Medicine business demonstrates our commitment to transforming care and advancing research in some of today’s most devastating neuropsychiatric and neurodegenerative disorders,” said Joaquin Duato, Chairman and Chief Executive Officer, Johnson & Johnson. “This acquisition further differentiates our portfolio, serves as a strategic near- and long-term growth catalyst for Johnson & Johnson and offers compelling value to patients, health systems and shareholders.” With this agreement, Johnson & Johnson adds Intra-Cellular Therapies’ CAPLYTA ® (lumateperone), a once-daily oral therapy approved to treat adults with schizophrenia, as well as depressive episodes associated with bipolar I or II disorder (bipolar depression), as a monotherapy and adjunctive therapy with lithium or valproate. The acquisition also includes ITI-1284, a promising Phase 2 compound being studied in generalized anxiety disorder (GAD) and Alzheimer’s disease-related psychosis and agitation, as well as a clinical-stage pipeline that further complements and strengthens Johnson & Johnson’s current areas of focus. “We are excited to welcome Intra-Cellular Therapies’ talented people and world-class expertise to Johnson & Johnson,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. “Together, we have an opportunity to impact even more patients living with neuropsychiatric and neurodegenerative disorders, significantly advancing care and helping improve the lives of millions worldwide.” “CAPLYTA ® ’s success and the robust pipeline we have built demonstrates the passion and dedication of our talented team, and we are proud of the hundreds of thousands of patients we have helped,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “Johnson & Johnson has a longstanding commitment to neuroscience, and we believe together, we can reach even more patients around the world.” In December 2024, Intra-Cellular Therapies announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for CAPLYTA ® as an adjunctive treatment for adults with major depressive disorder (MDD). In two global, double-blind, placebo-controlled Phase 3 studies, CAPLYTA ® , as an adjunctive treatment to antidepressants, demonstrated a statistically significant and clinically meaningful improvement in depressive symptoms, as measured by both clinician-rated and patient-reported outcomes. The safety profile of CAPLYTA ® in both studies was consistent with the existing body of clinical data for CAPLYTA ® , and no new safety concerns were identified. If approved, CAPLYTA ® has the potential to be the first treatment approved for MDD and depressive symptoms associated with bipolar I and II in more than 15 years. Additional Phase 3 trials are underway with CAPLYTA ® in bipolar I disorder with manic episodes or manic episodes with mixed features (bipolar mania). Positive topline results evaluating the efficacy and safety of CAPLYTA ® for the prevention of relapse in adult patients with schizophrenia were shared in November 2024. While its exact mechanism of action is unknown, CAPLYTA ® is uniquely characterized by high serotonin 5-HT 2A receptor occupancy and lower amounts of dopamine D 2 receptor occupancy at therapeutic doses. In short-term clinical studies across all three approved indications, CAPLYTA ® was similar to placebo in weight change, metabolic effects, and extrapyramidal symptoms, which are often cited as reasons for treatment discontinuation. The most common reported adverse events were somnolence/sedation, dizziness, nausea, and dry mouth. Across all three approved indications, CAPLYTA ® can be taken at any time of day with or without food and does not require titration, allowing adult patients to start treatment at the effective dose. “CAPLYTA ® has robust efficacy, proven safety and favorable tolerability across all three approved indications, without the need for dose titration frequently associated with this class of therapies,” said John Reed, M.D., Ph.D., Executive Vice President, R&D, Innovative Medicine, Johnson & Johnson. “With positive Phase 3 data in MDD as an adjunctive therapy and additional Phase 3 trials in other mental health disorders underway, we believe CAPLYTA ® has the potential to become a new standard of care for the treatment of some of today’s most prevalent and debilitating mental health disorders.” As the mental health crisis surges and the global population ages, more than one billion people worldwide – or 1 in every 8 people – are living with a neuropsychiatric or neurodegenerative disorder. In the United States: Transaction Details and Path to Completion Under the terms of the agreement, Johnson & Johnson will acquire all outstanding shares of Intra-Cellular Therapies for a payment of $132.00 per share in cash. Johnson & Johnson expects to fund the transaction through a combination of cash on hand and debt. Johnson & Johnson expects to maintain a strong balance sheet and to continue to support its stated capital allocation priorities of R&D investment, competitive dividends, value-creating acquisitions, and strategic share repurchases. The closing of the transaction is expected to occur later this year subject to applicable regulatory approvals, approval by Intra-Cellular Therapies’ stockholders and other customary closing conditions for a transaction of this type. Following completion of the transaction, Intra-Cellular Therapies’ common stock will no longer be listed for trading on the Nasdaq Global Select Market. Johnson & Johnson will provide commentary on any potential impact to Adjusted Earnings Per Share (EPS) from the transaction when it provides its initial full year 2025 guidance during the fourth quarter earnings call on Wednesday, January 22, 2025. Advisors Citi is serving as financial advisor to Johnson & Johnson, and Cravath, Swaine & Moore is serving as legal advisor. Centerview Partners LLC and Jefferies are serving as financial advisors to Intra-Cellular Therapies, and Davis Polk & Wardwell LLP is serving as legal advisor. Indication CAPLYTA ® (lumateperone) is indicated in adults for the treatment of schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. Important Safety Information Boxed Warnings: Contraindications: CAPLYTA ® is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA ® . Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria. Warnings & Precautions: Antipsychotic drugs have been reported to cause: Drug Interactions: CAPLYTA ® should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors. Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Dose reduction is recommended for patients with moderate or severe hepatic impairment. Adverse Reactions : The most common adverse reactions in clinical trials with CAPLYTA ® vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth. CAPLYTA ® is available in 10.5 mg, 21 mg, and 42 mg capsules. Please click here to see full Prescribing Information including Boxed Warning . About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at www.jnj.com/ . About Intra-Cellular Therapies, Inc. Intra-Cellular Therapies is a biopharmaceutical company founded on Nobel Prize-winning research that allows us to understand how therapies affect the inner workings of cells in the body. The company leverages this intracellular approach to develop innovative treatments for people living with complex psychiatric and neurologic diseases. For more information, please visit www.intracellulartherapies.com . ADDITIONAL INFORMATION AND WHERE TO FIND IT This press release may be deemed to be solicitation material in respect of the proposed acquisition of Intra-Cellular Therapies by Johnson & Johnson. In connection with the proposed transaction, Intra-Cellular Therapies intends to file relevant materials with the U.S. Securities and Exchange Commission (“SEC”), including Intra-Cellular Therapies’ proxy statement in preliminary and definitive form. INVESTORS AND STOCKHOLDERS OF INTRA-CELLULAR THERAPIES ARE URGED TO READ ALL RELEVANT DOCUMENTS FILED WITH THE SEC, INCLUDING INTRA-CELLULAR THERAPIES’ PROXY STATEMENT (WHEN THEY ARE AVAILABLE), BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION AND THE PARTIES TO THE PROPOSED TRANSACTION. Investors and stockholders of Intra-Cellular Therapies are or will be able to obtain these materials (when they are available) free of charge at the SEC’s website at www.sec.gov , or free of charge from Intra-Cellular Therapies’ website at www.intracellulartherapies.com . PARTICIPANTS IN THE SOLICITATION Johnson & Johnson and Intra-Cellular Therapies and certain of their respective directors and executive officers, under SEC rules, may be deemed to be “participants” in the solicitation of proxies from stockholders of Intra-Cellular Therapies in connection with the proposed transaction. Information about Johnson & Johnson’s directors and executive officers is available in Johnson & Johnson’s Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the SEC on February 16, 2024, and Johnson & Johnson’s definitive proxy statement for its 2024 annual meeting of stockholders, which was filed with the SEC on March 13, 2024. Information about Intra-Cellular Therapies’ directors and executive officers is available in Intra-Cellular Therapies’ Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the SEC on February 22, 2024, and Intra-Cellular Therapies’ definitive proxy statement for its 2024 annual meeting of stockholders, which was filed with the SEC on April 29, 2024. To the extent holdings of Johnson & Johnson’s or Intra-Cellular Therapies’ securities by their respective directors or executive officers have changed since the amounts set forth in such 2024 proxy statements, such changes have been or will be reflected on Initial Statements of Beneficial Ownership on Form 3 or Statements of Change in Ownership on Form 4 filed with the SEC, including the Form 3 filed by Sanjeev Narula on August 14, 2024 and the Form 4s filed by: Sharon Mates on August 23, 2024 , August 28, 2024 , August 30, 2024 and December 6, 2024 ; Joel S. Marcus on June 18, 2024 and June 25, 2024 ; Rory B. Riggs on June 18, 2024 , June 25, 2024 , July 2, 2024 , October 2, 2024 , October 15, 2024 and January 3, 2025 ; Eduardo Rene Salas on June 18, 2024 and June 25, 2024 ; Robert L. Van Nostrand on June 18, 2024 , June 21, 2024 , June 25, 2024 and July 2, 2024 ; Michael Halstead on November 14, 2024 ; Mark Neumann on August 20, 2024 ; and Sanjeev Narula on August 14, 2024 . Investors and stockholders of Intra-Cellular Therapies are or will be able to obtain these documents free of charge from the SEC’s website at www.sec.gov, from Johnson & Johnson on Johnson & Johnson’s website at www.jnj.com , from Intra-Cellular Therapies on Intra-Cellular Therapies’ website at www.intracellulartherapies.com or on request from Johnson & Johnson or Intra-Cellular Therapies. Additional information concerning the interests of Intra-Cellular Therapies’ participants in the solicitation, which may, in some cases, be different than those of Intra-Cellular Therapies’ stockholders generally, will be set forth in Intra-Cellular Therapies’ proxy statement relating to the proposed transaction when it becomes available. Footnotes i Non risk adjusted peak year sales including partner sales ii World Health Organization. Schizophrenia. Accessed December 2024. https://www.who.int/news-room/fact-sheets/detail/schizophrenia iii Regier DA, Farmer ME, Rae DS, et al. One–month prevalence of mental disorders in the United States and sociodemographic characteristics: the epidemiologic catchment area study. Acta Psychiatr Scand. (1993);88(1):35-47. doi:10.1111/j.1600-0447.1993.tb03411. iv US Census Bureau. 2010 US Census. Accessed December 23, 2024. https://www.census.gov/topics/population/data.html v Harvard Medical School, 2007. National Comorbidity Survey (NSC). (2017, August 21). Retrieved from https://www.hcp.med.harvard.edu/ncs/index.php . Data Table 2: 12-month prevalence DSM-IV/WMH-CIDI disorders by sex and cohort. vi Mayo Clinic. Bipolar disorder. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/bipolar-disorder/symptoms-causes/syc-20355955 . Published August 14, 2024. Accessed December 23, 2024. vii Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2021 National Survey on Drug Use and Health. Published December 2022. Accessed December 23, 2024. https://www.samhsa.gov/data/sites/default/files/reports/rpt39443/2021NSDUHFFRRev010323.pdf viii 2024 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2024;20(5):3708-3821. doi:10.1002/alz.13809. SOURCE: Johnson & Johnson

Patient Enrollment Ongoing in Phase 2 RECONNECT Trial of RE104 in Postpartum Depression (PPD); Topline Data Anticipated Mid-2025 Initiation of Phase 2 REKINDLE Trial of RE104 in Adjustment Disorder (AjD) Expected in Mid-2025 Advancing RE245, a Non-Psychedelic Serotonergic Neuroplastogen, through Preclinical Development Company to Present at 8th Annual Neuroscience Innovation Forum on January 12, 2025 in San Francisco, CA MORRISTOWN, N.J., Jan. 06, 2025 (GLOBE NEWSWIRE) -- Reunion Neuroscience Inc., a clinical-stage biopharmaceutical company committed to revolutionizing the treatment of underserved mental health disorders through the advancement of next-generation psychedelic-inspired therapeutic solutions, today announced program updates and anticipated 2025 milestones. The Company also announced that Greg Mayes, President and Chief Executive Officer, will present a corporate overview and participate in a panel discussion entitled “Future of Psychedelics” at the 8th Annual Neuroscience Innovation Forum, taking place January 12, 2025 in San Francisco, CA. “We are relentlessly committed to revolutionizing the treatment of mental health disorders, which impact millions of patients, families and caregivers,” said Greg Mayes, President and Chief Executive Officer of Reunion Neuroscience. “Our initial efforts are focused on RE104, a differentiated psychedelic designed to offer safe, fast-acting relief for patients who suffer from postpartum depression, adjustment disorder and other mental health conditions underserved by current treatment options. As we enter 2025, we are particularly encouraged by recent progress across our PPD program, where we remain on-track to report topline clinical data from our Phase 2 RECONNECT trial mid-year. We are grateful to the patients and physicians who are supporting our study, and to the many nonprofit organizations across the country that are building better awareness of maternal mental health and increased support for pregnant and postpartum women.” Mr. Mayes continued, “Also in 2025, we will continue to expand our pipeline, initiating clinical development of RE104 in adjustment disorder – a significant mental disorder for which there are no approved products – and progressing our second product candidate, RE245, through IND-enabling studies. We look forward to advancing both programs, as we aim to build an industry-leading pipeline of differentiated therapeutic solutions, which can deliver the full promise of psychedelic-inspired medicines to address the worldwide mental health crisis.” Program Updates and Upcoming Milestones RE104 is a proprietary, potential best-in-class, serotonergic neuroplastogen. RE-104 is designed as a single-dose psychedelic that offers a fast onset and shorter treatment duration, as well as reproducible pharmacokinetics. RE104 has potential across a variety of neuropsychiatric indications, including in PPD and AjD, where Reunion is focusing its initial clinical development efforts. Postpartum Depression (PPD): PPD is the most common complication of pregnancy and childbirth, with perinatal mood and anxiety disorders affecting one in five perinatal individuals up to one year after childbirth. RE104 is currently being evaluated in RECONNECT, a Phase 2 clinical trial evaluating the safety and efficacy of two doses of RE104 (30 mg and 1.5 mg) in reducing depressive symptoms in adult female patients with moderate-to-severe PPD.Reunion expects to complete patient enrollment and report topline clinical data from the RECONNECT trial in mid-2025. Adjustment Disorder (AjD): AjD, which is defined as the development of emotional or behavioral symptoms in response to an identifiable stressor, is among the most frequent diagnosis managed by psychiatrists globally. Reunion plans to evaluate RE104 in REKINDLE, a Phase 2 clinical trial evaluating the safety and efficacy of two doses of RE104 (30 mg and 1.5 mg) in reducing depressive and anxiety symptoms in patients with cancer and other medical illnesses, who are diagnosed with AjD.Reunion expects to initiate the REKINDLE trial in mid-2025. RE245 is a non-psychedelic serotonergic neuroplastogen designed to orally deliver 5HT2A-mediated neuroplasticity, resulting in therapeutic mental health benefits without hallucination. Reunion plans to initiate investigational new drug (IND)-enabling studies for RE245 in 2025 and to file an IND application in 2026. 8th Annual Neuroscience Innovation Forum Presentation: Reunion’s President and Chief Executive Officer, Greg Mayes, will present a corporate overview and participate in a panel discussion, “Future of Psychedelics,” at the 8th Annual Neuroscience Innovation Forum being held on January 12, 2025 in San Francisco, CA. Details of the presentation and panel discussion are as follows: Presentation: 11:35 a.m. PT (2:35 p.m. ET)Panel Discussion: 2:20 p.m. PT (5:20 p.m. ET). About RE104The Company’s lead product candidate, RE104, is a proprietary, potential best-in-class, patented prodrug of 4-OH-DiPT. Reunion designed RE104 to deliver a short duration psychedelic experience compared to longer duration psychedelics like psilocybin. In a Phase 1 clinical trial, RE104 produced a psychedelic state similar in intensity and quality to psilocybin, but lasting only about half the time (3-4 hours), while demonstrating a similar, favorable safety profile. RE104 is currently being evaluated in the RECONNECT Phase 2 (NCT06342310) clinical trial, a multicenter, randomized, double-blind, active dose-controlled clinical trial in moderate-to-severe postpartum depression (PPD) patients. Reunion plans to initiate the REKINDLE Phase 2 clinical trial, a randomized, double-blind, parallel-group, dose-controlled trial in adjustment disorder (AjD) in cancer and other medical illnesses. About RECONNECT The RECONNECT Phase 2 clinical trial (NCT06342310), a multicenter, randomized, double-blind, active dose-controlled clinical trial is evaluating the safety and efficacy of a single subcutaneous dose of RE104 in adult female patients with moderate-to-severe PPD. To learn more about the study and eligibility for enrollment, please visit www.ppdreconnectstudy.com. About Reunion Neuroscience Inc.Reunion Neuroscience is a clinical-stage biopharmaceutical company committed to revolutionizing the treatment of underserved mental health disorders through the advancement of next-generation psychedelic therapeutic solutions. In August of 2023, Reunion Neuroscience became a private company and in May 2024, the Company completed a Series A financing co-led by MPM BioImpact and Novo Holdings. Reunion is actively investigating the use of its lead product candidate, RE104, in postpartum depression and adjustment disorder, as well as in additional neuropsychiatric indications where there remains a significant unmet need that is not addressed by the current standard of care. For more information about the company, visit https://reunionneuro.com. For further information:IR Inquiries:Hannah DeresiewiczPrecision AQhannah.deresiewicz@precisionaq.com PR Inquiries:Ashley Murphy Precision AQashley.murphy@precisionaq.com