D2 receptor

New analyses suggest REXULTI was associated with reductions in overall neuropsychiatric symptoms and in agitation symptoms REXULTI was associated with reductions in occupational disruptiveness/caregiver distress as early as four weeks Efficacy of REXULTI for agitation symptoms confirmed across dementia severity, care setting, concomitant/prior medication use, and co-occurring neuropsychiatric symptoms REXULTI was associated with improvement in agitation symptoms in patients with and without psychosis symptoms at baseline PRINCETON, N.J. & DEERFIELD, Ill.--(BUSINESS WIRE)-- Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka) and Lundbeck U.S., the U.S. subsidiaries of H. Lundbeck A/S, (Lundbeck) presented new post hoc pooled analyses of two pivotal Phase 3 trials evaluating the safety and efficacy of REXULTI® (brexpiprazole) in patients with agitation associated with dementia due to Alzheimer’s disease.1 The posters were presented on March 16 at the American Association for Geriatric Psychiatry (AAGP) 2024 Annual Meeting in Atlanta. This press release features multimedia. View the full release here: REXULTI is the first treatment approved by the U.S. Food and Drug Administration (FDA) for agitation associated with dementia due to Alzheimer’s disease.2 Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric condition reported in approximately half of all patients with dementia due to Alzheimer’s disease and one of the most complex and stressful aspects of caring for people living with dementia due to Alzheimer’s disease.3 Agitation symptoms include behaviors such as pacing, gesturing, profanity, shouting, shoving, and hitting.4 Otsuka and Lundbeck presented three practice-relevant posters containing post hoc analyses on the efficacy of REXULTI in patients with agitation associated with dementia due to Alzheimer’s disease, and caregiver impact at the meeting. One poster utilized the Neuropsychiatric Inventory (NPI) to explore the relationship of REXULTI on neuropsychiatric symptoms relating to agitation and occupational disruptiveness/caregiver distress related to patients’ behavior. The NPI, which is administered through a structured caregiver interview, is comprised of 12 domains of neuropsychiatric symptoms including agitation/aggression, irritability/lability, and disinhibition. Each domain is scored from best to worst based on frequency, severity, and occupational disruptiveness/caregiver distress. The analysis demonstrated that REXULTI was associated with reductions in overall neuropsychiatric symptoms and in agitation symptoms (as captured by the NPI) compared with placebo over 12 weeks. In addition, REXULTI was associated with a greater reduction in occupational disruptiveness/caregiver distress total score compared to placebo, with separation observed as early as Week 4.1 Another poster explored the efficacy of REXULTI on symptoms of agitation across different patient characteristic subgroups that are common in clinical practice, including baseline dementia severity, care setting, concomitant/prior medication use, and baseline co-occurring NPI symptoms (excluding agitation). A responder analysis based on a meaningful within-patient change threshold of ≥20-point reduction from baseline to Week 12 in the CMAI Total score was also conducted. The post-hoc analysis demonstrated that REXULTI was associated with greater improvement in symptoms of agitation than placebo across all subgroups as measured by the change from baseline in Cohen-Mansfield Agitation Inventory (CMAI) total score at Week 12.5 The final poster looked at the efficacy and safety of REXULTI in patients grouped by baseline psychosis status (with psychosis and without psychosis), with approximately a quarter of patients presenting with psychosis symptoms at baseline. The analysis showed fixed-dose REXULTI 2 or 3 mg/day was associated with greater improvements in agitation symptoms compared with placebo in both subgroups, as measured by the change in CMAI total score at Week 12. In addition, the safety and tolerability of REXULTI 0.5-3mg/day was similar between the subgroups.6 “It’s well known that the effects of dementia due to Alzheimer’s disease extend beyond the patient to caregivers whose lives are often disrupted in order to meet the significant demands of care,” said George T. Grossberg, MD, Department of Psychiatry and Behavioral Neuroscience at Saint Louis University School of Medicine. “These new analyses are important because they are the first to explore the potential impact of addressing agitation symptoms with brexpiprazole on caregiver-reported distress.” “These data reinforce the urgency to treat agitation separately from dementia due to Alzheimer’s disease and gives prescribers further confidence to choose an FDA-approved therapy to help address these symptoms,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “We greatly appreciate the efforts of the caregivers and their families that participated in these important clinical trials.” “Family caregivers typically spend more than 20 hours a week caring for a loved one with Alzheimer’s disease,”7 said Johan Luthman, executive vice president, Lundbeck Research & Development. “The breadth of data presented at AAGP represents our continued commitment to understanding the full potential of REXULTI on agitation associated with dementia due to Alzheimer’s disease.” About Agitation Associated with Dementia Due to Alzheimer’s Disease Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric symptom that is reported in approximately half of all patients with dementia due to Alzheimer’s disease.3 The condition has a large impact on the quality of life for the patients, family members, and caregivers.3,8 Agitation associated with dementia due to Alzheimer’s disease covers a large group of behaviors occurring in patients with dementia due to Alzheimer’s disease, such as pacing, gesturing, profanity, shouting, shoving, and hitting.8 Symptoms of agitation are also a consistent predictor of nursing home admission in patients with dementia, including those with Alzheimer’s disease.9-11 About Brexpiprazole Brexpiprazole was approved in the U.S. in 2015 as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively. It was approved by the Ministry of Health, Labour and Welfare in Japan and by the European Medicines Agency (EMA) in 2018 for the treatment of schizophrenia. Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown, however the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole) INDICATIONS: REXULTI is a prescription medicine used: along with antidepressant medicines to treat major depressive disorder (MDD) in adults to treat schizophrenia in adults and children ages 13 years and older to treat agitation that may happen with dementia due to Alzheimer’s disease REXULTI should not be used as an “as needed” treatment for agitation that may happen with dementia due to Alzheimer’s disease. It is not known if REXULTI is safe and effective in children with MDD. It is not known if REXULTI is safe and effective in children under 13 years of age with schizophrenia. IMPORTANT SAFETY INFORMATION: Increased risk of death in elderly people with dementia-related psychosis. Medicines like REXULTI can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). REXULTI is not approved for the treatment of people with dementia-related psychosis without agitation that may happen with dementia due to Alzheimer’s disease. Increased risk of suicidal thoughts and actions. REXULTI and antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Depression and other mental illnesses are the most important causes of suicidal thoughts and actions. Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. Report any change in these symptoms immediately to the doctor. Do not take REXULTI if you are allergic to brexpiprazole or any of the ingredients in REXULTI. REXULTI may cause serious side effects, including: Cerebrovascular problems, including stroke, in elderly people with dementia-related psychosis that can lead to death. Neuroleptic malignant syndrome (NMS) is a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS: high fever; changes in your pulse, blood pressure, heart rate, and breathing; stiff muscles; confusion; increased sweating Uncontrolled body movements (tardive dyskinesia). REXULTI may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking REXULTI. Tardive dyskinesia may also start after you stop taking REXULTI. Problems with your metabolism such as: high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take REXULTI. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start, or soon after you start REXULTI and then regularly during long term treatment with REXULTI. Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with REXULTI: feel very thirsty feel very hungry feel sick to your stomach need to urinate more than usual feel weak or tired feel confused, or your breath smells fruity increased fat levels (cholesterol and triglycerides) in your blood. Your healthcare provider should check the fat levels in your blood before you start, or soon after you start REXULTI, and then periodically during treatment with REXULTI. weight gain. You and your healthcare provider should check your weight before you start and often during treatment with REXULTI. Unusual and uncontrollable (compulsive) urges. Some people taking REXULTI have had strong unusual urges, to gamble and gambling that cannot be controlled (compulsive gambling). Other compulsive urges include sexual urges, shopping, and eating or binge eating. If you or your family members notice that you are having new or unusual strong urges or behaviors, talk to your healthcare provider. Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with REXULTI. Decreased blood pressure (orthostatic hypotension) and fainting. You may feel dizzy, lightheaded or pass out (faint) when you rise too quickly from a sitting or lying position. Falls. REXULTI may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause fractures or other injuries. Seizures (convulsions). Problems controlling your body temperature so that you feel too warm. Do not become too hot or dehydrated during treatment with REXULTI. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water. Difficulty swallowing that can cause food or liquid to get into your lungs. Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. Do not drive a car, operate machinery, or do other dangerous activities until you know how REXULTI affects you. REXULTI may make you feel drowsy. Before taking REXULTI, tell your healthcare provider about all of your medical conditions, including if you: have or have had heart problems or a stroke have or have had low or high blood pressure have or have had diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start REXULTI and during treatment with REXULTI. have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low levels of HDL cholesterol have or have had seizures (convulsions) have or have had kidney or liver problems have or have had a low white blood cell count are pregnant or plan to become pregnant. REXULTI may harm your unborn baby. Taking REXULTI during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take REXULTI during pregnancy. Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with REXULTI. There is a pregnancy exposure registry for women who are exposed to REXULTI during pregnancy. If you become pregnant during treatment with REXULTI, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit . are breastfeeding or plan to breastfeed. It is not known if REXULTI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with REXULTI. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. REXULTI and other medicines may affect each other causing possible serious side effects. REXULTI may affect the way other medicines work, and other medicines may affect how REXULTI works. Your healthcare provider can tell you if it is safe to take REXULTI with your other medicines. Do not start or stop any medicines during treatment with REXULTI without first talking to your healthcare provider. The most common side effects of REXULTI include weight gain, sleepiness, dizziness, common cold symptoms, and restlessness or feeling like you need to move (akathisia). These are not all the possible side effects of REXULTI. For more information, ask your healthcare provider or pharmacist. You are encouraged to report side effects of REXULTI (brexpiprazole). Please contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 ( ). Please read FULL PRESCRIBING INFORMATION, including BOXED WARNING, and MEDICATION GUIDE for REXULTI. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at About Lundbeck Lundbeck US refers to the wholly owned US subsidiaries of H. Lundbeck A/S (HLUNa / HLUNb, HLUNA DC / HLUNB DC), a global pharmaceutical company specialized in brain diseases, including Lundbeck LLC and Lundbeck Pharmaceuticals LLC. For more than 70 years, we have been at the forefront of neuroscience research. We are tirelessly dedicated to restoring brain health, so every person can be their best. We have approximately 5,400 employees in more than 50 countries, and our products are available in more than 100 countries. Our research programs tackle some of the most complex challenges in neuroscience, and our pipeline is focused on bringing forward transformative treatments for brain diseases for which there are few, if any therapeutic options. We have research facilities in Denmark and the United States, and our production facilities are located in Denmark, France and Italy. In the United States, H. Lundbeck A/S subsidiaries, including Lundbeck LLC and Lundbeck Pharmaceuticals LLC, employ more than 1,000 people focused solely on accelerating therapies for brain disorders. With a special commitment to the lives of patients, families and caregivers, Lundbeck US actively engages in a broad range of initiatives each year that support patient communities. For additional information, we encourage you to visit us at lundbeck.com/us and connect with us on LinkedIn and Twitter at @LundbeckUS. References Brubaker M, Wang D, Chumki S, et al. Efficacy of Brexpiprazole Across Agitation Behaviors in Alzheimer’s Disease, Including Impact on Caregivers, Analyzed Using the Neuropsychiatric Inventory: a Post Hoc Pooled Analysis of Randomized, Fixed-dose, Placebo-controlled Trials. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. FDA News Release. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer’s Disease. Published: May 11, 2023. Last accessed: Feb 20, 2024. Available at: Halpern R, Seare J, Tong J, Hartry A, Olaoye A, Aigbogun MS. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry. 2019;34(3):420-431. Cummings J, Mintzer J, Brodaty H, et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr. 2015;27(1):7-17. Brubaker M, Wang D, Chumki S, et al. Efficacy of Brexpiprazole in Patients With Agitation Associated With Dementia Due to Alzheimer’s Disease Analyzed by Patient Characteristics: a Post Hoc Pooled Analysis of Randomized, Fixed-dose, Placebo-controlled Trials. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. Behl S, Chang D, Chen D, et. al. Efficacy of Brexpiprazole in Patients with Agitation Associated With Alzheimer’s Dementia Analyzed by Presence or Absence of Psychosis: a Pooled Analysis. American Association for Geriatric Psychiatry (AAGP), Atlanta, Ge., March-15-18, 2024. Alzheimer’s Association. 2015 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2015;11(3)332. Last accessed: 07 Mar, 2024. Available at: Fillit H, Aigbogun MS, Gagnon-Sanschagrin P, et al. Impact of agitation in long-term care residents with dementia in the United States. Int J Geriatr Psychiatry. 2021;36(12):1959-1969. Gaugler JE, Yu F, Krichbaum K, Wyman JF. Predictors of nursing home admission for persons with dementia [published correction appears in Med Care. 2009 May;47(5):606]. Med Care. 2009;47(2):191-198. Kales HC, Chen P, Blow FC, Welsh DE, Mellow AM. Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression. Am J Geriatr Psychiatry. 2005;13(6):441-449. Yaffe K, Fox P, Newcomer R, et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA. 2002;287(16):2090-2097.

Gut bacteria and a diet rich in the amino acid tryptophan can play a protective role against pathogenic E. coli, which can cause severe stomach upset, cramps, fever, intestinal bleeding and renal failure. Gut bacteria and a diet rich in the amino acid tryptophan can play a protective role against pathogenic E. coli, which can cause severe stomach upset, cramps, fever, intestinal bleeding and renal failure, according to a study published March 13 in Nature. The research reveals how dietary tryptophan -- an amino acid found mostly in animal products, nuts, seeds, whole grains and legumes -- can be broken down by gut bacteria into small molecules called metabolites. It turns out a few of these metabolites can bind to a receptor on gut epithelial (surface) cells, triggering a pathway that ultimately reduces the production of proteins that E. coli use to attach to the gut lining where they cause infection. When E. coli fail to attach and colonize the gut, the pathogen benignly moves through and passes out of the body. The research describes a previously unknown role in the gut for a receptor, DRD2. DRD2 has otherwise been known as a dopamine (neurotransmitter) receptor in the central and peripheral nervous systems. "It's actually two completely different areas that this receptor could play a role in, which was not appreciated prior to our findings," said Pamela Chang, associate professor of immunology in the College of Veterinary Medicine and of chemical biology in the College of Arts and Sciences. "We essentially think that DRD2 is moonlighting in the gut as a microbial metabolite sensor, and then its downstream effect is to help protect against infection." Samantha Scott, a postdoctoral researcher in Chang's lab, is first author of the study, "Dopamine Receptor D2 Confers Colonization Resistance via Microbial Metabolites." Now that Chang, Scott and colleagues have identified a specific pathway to help prevent E. coli infection, they may now begin studying the DRD2 receptor and components of its downstream pathway for therapeutic targets. In the study, the researchers used mice infected with Citrobacter rodentium, a bacterium that closely resembles E. coli, since certain pathogenic E. coli don't infect mice. Through experiments, the researchers identified that there was less pathogen and inflammation (a sign of an active immune system and infection) after mice were fed a tryptophan-supplemented diet. Then, to show that gut bacteria were having an effect, they gave the mice antibiotics to deplete microbes in the gut, and found that the mice were infected by C. rodentium in spite of eating a tryptophan diet, confirming that protection from tryptophan was dependent on the gut bacteria. Then, using mass spectrometry, they ran a screen to find the chemical identities of tryptophan metabolites in a gut sample, and identified three such metabolites that were significantly increased when given a tryptophan diet. Again, based on pathogen levels and inflammation, when these three metabolites alone were fed to the mice, they had the same protective effect as giving the mice a full tryptophan diet. Switching gears, the researchers used bioinformatics to find which proteins (and receptors) might bind to the tryptophan metabolites, and from a long list they identified three related receptors within the same family of dopamine receptors. Using a human intestinal cell line in the lab, they were able to isolate receptor DRD2 as the one that had the protective effect against infection in the presence of tryptophan metabolites. Having identified the metabolites and the receptor, they analyzed the downstream pathway of DRD2 in human gut epithelial cells. Ultimately, they found that when the DRD2 pathway was activated, the host's ability to produce an actin regulatory protein was compromised. C. rodentium (and E. coli) require actin to attach themselves to gut epithelial cells, where they colonize and inject virulence factors and toxins into the cells that cause symptoms. But without actin polymerization they can't attach and the pathogen passes through and clears. The experiments revealed a new role of dopamine receptor DRD2 in the gut that controls actin proteins and affects a previously unknown pathway for preventing a pathogenic bacteria's ability to colonize the gut. Jingjing Fu, a former postdoctoral researcher in Chang's lab, is a co-author. The study was supported by the Arnold and Mabel Beckman Foundation, a President's Council of Cornell Women Affinito-Stewart Grant, the National Institutes of Health and a Cornell Institute of Host-Microbe Interactions and Disease Postdoctoral Fellowship.

Revenue in 2023 reached € 5.25 billion (-5%; -6% CER1), net sales were € 4.87 billion (-5%; -6% CER1) – in-line with financial guidance Strong performance by newly launched growth drivers (net sales growth at Act rates): EVENITY® +140%, FINTEPLA® +94%, BIMZELX® +323%. RYSTIGGO® with € 19 million since July, ZILBRYSQ® launched globally since Q1 2024 Underlying profitability (adj. EBITDA2) was € 1.35 billion (+7%; -1% CER1), 25.7% of revenue – better than the guidance due to higher EVENITY® contribution and good cost management U.S. FDA accepted the filings of BIMZELX® for psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). The application for hidradenitis suppurativa (HS) has also been submitted to FDA. FDA action and potential approvals expected for all indications before the end of 2024 Financial guidance for 2024: Revenue expected to grow to € 5.5-5.7 billion, adjusted EBITDA2 23.0-24.5% of revenue, Core EPS3 of € 3.70-4.40 BRUSSELS, Feb. 28, 2024 /PRNewswire/ -- UCB Full-Year Report 2023 – regulated information "Our 2023 performance showcases our unwavering commitment to ensuring people with severe diseases can live the life they like, as free as possible from challenges of disease, reaching more than 3.2 million patients globally with severe immunological and neurological conditions. In the last 14 months we obtained 14 approvals, across 6 patient populations and across 3 continents, fuelling our growth for a decade plus. As an example, superior patient experience and UCB's dedication have allowed to double the number of patients using BIMZELX ® in Europe over six months," Jean-Christophe Tellier, CEO UCB commented. "For future growth, we are studying innovative, potential medicines for 10 patient populations in 12 clinical development programs with expected news flow in 2024. What guides us is our belief that everyone deserves to live the best life that they can. We are therefore pleased with the growing access to our medicines across geographies, and we continue to decrease our greenhouse gas emissions in line with our commitment to reach net zero emissions." FY 2023 revenue reached € 5.25 billion (-5%; -6% CER1). Net sales reached € 4.87 billion (-5%; -6% CER1), based on the stable performance of CIMZIA® and the strong growth of BRIVIACT®, FINTEPLA® and BIMZELX®. As expected, this was more than offset by the contracting effects from the losses of exclusivity of two products. Underlying profitability (adjusted EBITDA2) reached € 1.35 billion (7%; -1% CER1), despite lower revenue due to the losses of exclusivity, higher operating expenses – reflecting the investments into the future growth of UCB, namely into product launches - and compensated by higher operating income. Profit amounted to € 343 million (-18%; -34% CER1). Core EPS3 were € 4.20 after € 4.37 in 2022. The Board of Directors of UCB proposes a dividend of € 1.36 per share (gross), + 3 cents. Sandrine Dufour, CFO UCB says: "A year with good product growth and strong launches - we are pleased to deliver again solid financial results. As expected, we're seeing the impacts from the losses of exclusivity for two products diminishing in the second half and thanks to the strong revenue performance of our growth assets, we returned to growth in the second half with almost +3%. Continued smart resource allocation and a strong contribution from EVENITY® enabled us to invest in the product launches. In 2024, we will accelerate our investments launching three products around the globe, including a direct to consumer (DTC) campaign in the U.S. for BIMZELX®, previously slated for 2023. We are on our way to deliver growth for a decade plus. Our financial guidance for 2024 foresees a growing top line and an almost stable adjusted EBITDA margin. Our commitment for 2025 for growing the top line to at least € 6 billion and an improved margin stands." Regulatory and Clinical Pipeline Update UCB continuously innovates and strives to find new ways to deliver solutions to people living with severe immunological and neurological diseases, leading in 2023 to a clinical development pipeline with 12 clinical programs ongoing spanning 10 different medicines, set to help 10 different patient populations. Since January 2023 and in the key regions U.S., EU and Japan, UCB obtained 14 approvals across six patient populations. 8 regulatory reviews are ongoing. Below the details since the Half-Year Report 2023: Regulatory Update In June 2023, E KEPPRA® (levetiracetam) was approved in Japan for the treatment of partial-onset epileptic seizures in young patients (1m-<4years of age). In July 2023, the European Medicines Agency (EMA) has accepted for review the marketing authorization application of bimekizumab for the treatment of adults with moderate to severe hidradenitis suppurativa (HS), a chronic, recurrent, and debilitating skin condition with high unmet medical need. In July 2023, UCB submitted the marketing authorization application for the epilepsy medicine BRIVIACT® (brivaracetam) to PMDA in Japan. This application is for the treatment of partial onset seizures (POS) with or without secondary generalization in adult patients (≥16 years of age) with monotherapy and adjunctive therapy. In September 2023, UCB announced the approval of RYSTIGGO® (rozanolixizumab) and ZILBRYSQ® (zilucoplan) for the treatment of adult patients with generalized myasthenia gravis (gMG) in Japan, where RYSTIGGO® is indicated for patients inadequately responding to corticosteroids or non-corticosteroid immunosuppressants and ZILBRYSQ® is indicated for patients who inadequately respond to steroids or other immunosuppressants. In February 2023, PMDA in Japan accepted for review the filing of rozanolixizumab in a priority review. In October 2023, UCB announced U.S. FDA approval of ZILBRYSQ® (zilucoplan) for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive (anti-AChRAb+). ZILBRYSQ® is the first once-daily subcutaneous, targeted C5 complement inhibitor for gMG. It is the only once-daily gMG-targeted therapy for self-administration. In October 2023, the U.S. FDA approved BIMZELX® (bimekizumab-bkzx), the first and only IL-17A and IL-17F inhibitor, for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In November 2023, UCB filed bimekizumab for the treatment of hidradenitis suppurativa (HS), a chronic, painful, and debilitating skin condition, with PMDA in Japan. In December 2023, ZILBRYSQ® (zilucoplan) was approved in the European Union for the treatment of adults with gMG who are anti-AChRAb+. In September 2023, UCB received CHMP positive opinion for zilucoplan for the treatment of adults with gMG in Europe. In December 2023, BIMZELX® was approved in Japan for the treatment of adult patients with active psoriatic arthritis (PsA), adult patients with active ankylosing spondylitis (AS) and adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA). In January 2023, PMDA in Japan had accepted for review the filing for BIMZELX® in these indications. In early January 2024, RYSTIGGO® (rozanolixizumab) was approved in the European Union for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. In November 2023, UCB received the CHMP positive opinion for rozanolixizumab for treatment of adults with generalized myasthenia gravis in Europe. In February 2024, UCB announced that the U.S. FDA accepted the supplemental biologics license applications (sBLA) seeking approval of BIMZELX® (bimekizumab-bkzx) for three new spondyloarthritides indications: psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). The fourth sBLA for hidradenitis suppurativa (HS) has also been submitted to FDA. UCB expects FDA action and potential approvals for all indications before the end of 2024. Pipeline Update In November 2023, first patients were included in a phase 2a study with UCB0022. UCB0022 is designed to enhance the potency of endogenous dopamine 'when and where needed'. UCB0022 is an orally available, brain-penetrant, small molecule acting as a Dopamine-1 receptor positive allosteric modulator. UCB0022 could bring, as symptomatic treatment, significant positive impact on the quality of life of people who are suffering from Parkinson's symptoms despite an adequately dosed treatment without bothersome side effects that can result from Dopamine-receptor overstimulation. First results are expected in H1 in 2025. During H2 2023, UCB9741 and UCB1381 progressed successfully and moved into Phase 2a status with first headline results expected in H2 2024. Atopic Dermatitis (AtD) is a common inflammatory skin disorder with higher prevalence rates among children. Despite evolving standard of care, unmet needs for moderate to severe AtD patients persist. Multiple pathways are believed to be the driver of pathobiology in AtD, as such UCB is developing two anti-bodies targeting distinct pathways. All other clinical studies are continuing as planned, with headline results expected for 11 programs in 2024. Net sales break-down by key products Due to rounding, some financial data may not add up in the tables. CIMZIA® (certolizumab pegol) reached more than 180 000 people living with inflammatory TNF-mediated diseases. CIMZIA® is showing a stronger growth than the anti-TNF market – based on differentiation. CIMZIA® is offering treatment for women of childbearing age across 6 indications and for rheumatoid arthritis patients with high rheum factor levels. In Europe as well as in international markets growth trend continues. Volume growth in the U.S. remains robust with 5% plus. Also in Japan, volume growth was positive but over-compensated by the regular mandatory price cut. VIMPAT® (lacosamide) was accessed by over 500 000 people living with epilepsy and is experiencing generic competition since March 2022 in the U.S. and since September 2022 in Europe due to loss of exclusivity. In Japan, the net sales show continued growth. KEPPRA® (levetiracetam) reached over 1.7 million people living with epilepsy. Net sales went down due to continued generic erosion in Japan since 2022. In all other markets, KEPPRA® is off patent for more than a decade. BRIVIACT® (brivaracetam), was used by 190 000 people living with epilepsy and showed significant growth in all regions it is available to patients. BRIVIACT® is currently under regulatory review in Japan. BRIVIACT® has a different mode of action from Vimpat® and differentiates from KEPPRA®. FINTEPLA® (fenfluramine) reached more than 3 000 patients and their families living with seizures associated with rare epileptic syndromes - Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Partner Nippon Shinyaku in Japan books the in-market sales. FINTEPLA® was added to the UCB portfolio in March 2022. Following a settlement in a patent dispute in late 2023, UCB is now considering Q4 2033 as a later loss of exclusivity in the U.S. BIMZELX® (bimekizumab) is available to people living with psoriasis in more than 40 countries, including the U.S. since mid-November 2023. Additionally, it is available to people living with active psoriatic arthritis (PsA), with active ankylosing spondylitis (AS) and active non-radiographic axial spondyloarthritis (nr-axSpA) in Europe since May 2023 and in Japan since December 2023. More than 18 000 patients had access to the product. NAYZILAM® (midazolam) Nasal SprayCIV, a nasal rescue treatment for epilepsy seizure clusters in the U.S. reached over 70 000 patients and net sales of € 94 million, a plus by 21% (24% CER) EVENITY® (romosozumab) since launch globally reached more than 600 000 women living with postmenopausal osteoporosis at high risk of fracture. Net sales in Europe increased to € 60 million after € 25 million in 2022. EVENITY® is being launched successfully globally by Amgen, Astellas and UCB since 2019, with net sales outside Europe reported by the partners. EVENITY® showed strong growth annualizing worldwide sales of more than US$ 1 billion. The worldwide profit contribution from EVENITY® is recognized under 'Other operating income'. RYSTIGGO® (rozanolixizumab-noli), a new treatment option for people living with generalized myasthenia gravis (gMG) was launched in the U.S. in July 2023. In 2023, net sales amounted to € 19 million. At the end of 2023, RYSTIGGO® was launched in Japan and the launches throughout Europe are starting in Q1 2024. "The statutory auditor has issued an unqualified report with no emphasis of matter paragraph dated 27 February 2024 on the company's consolidated accounts as of and for the year ended 31 December 2023, and has confirmed that the accounting data reported in the accompanying press release is consistent, in all material respects, with the accounts from which it has been derived." Revenue in 2023 reached € 5 252 million (-5%; -6% CER1) and net sales were € 4 867 million (-5%; -6% CER1). This was driven by the continued growth of UCB's product portfolio – namely BRIVIACT®, NAYZILAM® and FINTEPLA® showed double digit growth. CIMZIA® is the largest drug in the portfolio, showing stable performance and an increase at constant rates. EVENITY® as well as newly launched BIMZELX® more than doubled net sales. This performance was over-compensated by the known effects of the loss of exclusivity for VIMPAT® in the U.S. and Europe and E KEPPRA® in Japan. Royalty income and fees were € 77 million (-9%; -7% CER1) and other revenue went up by 5% (6% CER1) to € 308 million due to continued partnership activities, milestones and other payments from R&D partners and include a one-time amount of € 70 million from a milestone. Adjusted Gross profit (Gross Profit before "amortization of intangible assets linked to sales") was € 4 033 million (-5%; -6% CER1) and well in-line with the net sales performance. The adjusted gross margin remained stable at 76.8% as in 2022. Gross profit after "amortization of intangible assets linked to sales" reached € 3 545 million – a gross margin of 67.5% after 69.7% in 2022 and reflecting the addition of FINTEPLA® amortization. This amortization has been revised in late 2023 following a settlement in a patent dispute in the U.S. UCB is now considering Q4 2033 as the loss of exclusivity in the U.S. Operating expenses declined to € 2 888 million (-9%; -7% CER1) reflecting higher marketing and selling expenses, lower research and development expenses, slightly higher general and administration expenses and an "other operating income" which more than doubled. Total operating expenses are consisting of: 7% higher marketing and selling expenses of € 1 594 million (+10% CER1) – focused reallocation and cost discipline allowed to invest behind the launches and pre-launch activities for UCB's growth drivers: Global FINTEPLA® launch activities in two indications, global BIMZELX® launch activities in up to four indications, global launch activities for RYSTIGGO® and ZILBRYSQ®. 2% lower research and development expenses of € 1 630 million (-1% CER1) reflect the continued investments in UCB's progressing R&D pipeline today encompassing 10 potential new treatment options in clinical studies for patients living with severe diseases in 5 phase 3 trials and 7 proof-of-concept (phase 2a) trials as well as ongoing earlier research activities. The R&D ratio reached 31% in 2023 after 30% in 2022 due to lower revenue. 2% higher general and administrative expenses of € 230 million (+3% CER) Other operating income went up to € 566 million following € 216 million in 2022 – driven by the net contribution of € 368 million (+53%) from EVENITY®. Other 'other operating income' was from the sale of a portfolio of established brands in Europe (€ 145 million), in early 2023. Underlying operational profitability – adjusted EBITDA2 – increased by 7% to € 1 349 million (-1% CER1) due to efficient performance and cost management: lower revenue due to generic erosion, high operating expenses - reflecting the investments into the future growth of UCB, namely into product launches - and compensated by high operating income. The adjusted EBITDA ratio for 2023 (in % of revenue) reached 25.7%, after 22.8% in 2022. Total impairment, restructuring and other expenses decreased to € 53 million, after € 90 million in 2022. In 2022, this was mainly driven by fees and restructuring expenses related to the acquisition of Zogenix in March 2022. Net financial expenses went up to € 163 million from € 74 million, based on higher interest rates as well as higher interest cost due to higher net debt in connection with the acquisition of Zogenix in March 2022. Also, positive currency income in 2022 did not reoccur in 2023. Income tax expenses were € 98 million compared to € 91 million in 2022. The average effective tax rate was 22% compared to 18% in 2022, reflecting the lower earnings and the earnings mix. Profit amounted to € 343 million (-18%; -34% CER1). Core earnings per share, adjusted for the after-tax impact of to be adjusted items, the financial one-offs, the after-tax contribution from discontinued operations and the net amortization of intangibles linked to sales, reached € 4.20 after € 4.37 in 2022, based on stable 190 million weighted average shares outstanding. Dividend - The Board of Directors of UCB proposes a dividend of €1.36 per share (gross), +2%. Financial Guidance 2024 - The year 2024 will be marked by intense ongoing global launches of the UCB growth drivers, BIMZELX®, RYSTIGGO®, ZILBRYSQ® and FINTEPLA® as well as EVENITY®. For 2024, UCB is aiming for an increase of revenues to the range of € 5.5 - € 5.7 billion taking into account the launches and the continued solid contributions from the existing product portfolio. UCB will accelerate investments in launches around the globe to offer potential new solutions for people living with severe diseases and remains committed to invest into research and development advancing its late-stage and early development pipeline. At the same time, UCB will continue to be cost disciplined and, as in 2023, to actively manage the tail of its portfolio. Underlying profitability, adjusted EBITDA, is expected in the range of 23.0% - 24.5% of revenue. Core earnings per share are therefore expected in the range of € 3.70 - 4.40 per share – based on an average of 190 million shares outstanding. The figures for the financial guidance 2024 as mentioned above are calculated on the same basis as the actual figures for 2023. Guidance for 2025: UCB confirms its growth ambition for 2025 based on the strong product portfolio and the strong growth drivers. Revenue in 2025 is expected to reach at least € 6 billion and the underlying profitability (adjusted EBITDA) at the low end of the range of low to mid-thirties in percent of revenue. Find the financial reports on UCB website: Today, UCB will host a conference call/video webcast at 08.00 (EST) / 13.00 (GMT) / 14.00 (CET) Register here: For further information, contact UCB: Check out our IR App on the App Store and Google Play About UCB UCB, Brussels, Belgium ( ) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9 000 people in approximately 40 countries, the company generated revenue of € 5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news Forward looking statements This press release contains forward-looking statements, including, without limitation, statements containing the words "potential", "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will", "continue" and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guaranteeing future performance and are subject to known and unknown risks, uncertainties, and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include but are not limited to: global spread and impacts of wars and pandemics, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB's efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB's products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB's data and systems. Given these uncertainties, you are cautioned not to place any undue reliance on such forward-looking statements. These forward-looking statements are made only as of the date of this press release, and do not reflect any potential impacts from the evolving conflicts, wars, pandemics, as well as any other adversity, unless indicated otherwise. The company continues to follow the development diligently to assess the financial significance of these events, as the case may be, to UCB. UCB expressly disclaims any obligation or duty to update any forward-looking statements in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations. View original content to download multimedia: SOURCE UCB Company Codes: EuronextBrussels:UCB, OTC-PINK:UCBJY