Alicia, living with atopic dermatitis. Immune inflammatory diseases Non-melanoma skin cancer Other skin diseases Key products in other areas Atopic dermatitis Psoriasis Actinic keratosis Acne Onychomycosis 1 Koszorú K, Borza J, Gulácsi L, Sárdy M. Quality of life in patients with atopic dermatitis. Cutis. 2019 Sep;104(3):174-177. 2 Barbarot S, et al. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018 Jun;73(6):1284-1293. doi: 10.1111/all.13401. Epub 2018 Feb 13. PMID: 29319189. 3 Silverberg J, et al. Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417-428. 4 Bernardo D, et al. Lebrikizumab for the Treatment of Moderate-to-Severe Atopic Dermatitis. Am J Clin Dermatol. 2023;24, 753– 764. 5 Moyle M, et al. Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches. Exp Dermatol. 2019;28(7):756–768. 6 Gonçalves F, et al. Selective IL-13 inhibitors for the treatment of atopic dermatitis. Drugs Context 2021;10:2021-1-7. 7 Okragly A, et al. Binding, Neutralization and Internalization of the Interleukin-13 Antibody, Lebrikizumab. Dermatol Ther (Heidelb). 2023;13(7):1535-1547. 8 Ultsch M, et al. Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab. J Mol Biol. 2013;425(8):1330-1339. 9 Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2023;doi:10.1056/NEJMoa2206714. 10 Simpson EL et al. Efficacy and safety of Lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: a randomized clinical trial (ADhere). JAMA Dermatol. Published online January 11, 2023; doi:10.1001/jamadermatol.2022.5534. 11 Guttman-Yassky E, et al. Efficacy and Safety of Lebrikizumab Is Maintained to Two Years in Patients With Moderate-to-Severe Atopic Dermatitis. Presented at the Fall Clinical Dermatology Conference; October 20, 2023. 12 Stein Gold L, et al. Safety of Lebrikizumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: An Integrated Analysis of Eight Clinical Trials. Am J Clin Dermatol. 2023 Jul;24(4):595-607. doi: 10.1007/s40257-023-00792-6. Epub 2023 May 17. PMID: 37195407; PMCID: PMC10191071. 13 Blauvelt A, et al. Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials. British Journal of Dermatology. 2023; ljad022, https://doi.org/10.1093/bjd/ljad022. 14 Parisi R, Iskandar IYK, Kontopantelis E, Augustin M, Griffiths CEM, Ashcroft DM et al. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study. BMJ. 2020 May;36:m1590. doi:10.1136/bmj.m1590. 15 Dowlatshahi EA, Wakkee M, Arends LR, Nijsten T. The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: A systematic review and meta-analysis. J Invest Dermatol. 2014 Jun;134(6):1542–1551. doi: 10.1038/jid.2013.508. Epub 2013 Nov 27. PMID: 24284419. 16 Mrowietz U, et al. Presented at the 25th World Congress of Dermatology (WCD) July 3-8 ,2023, Singapore, Abstract 799. 17 Topp CW, et al. The WHO-5 Well-Being Index: a systematic review of the literature. Psychother Psychosom. 2015;84:167–76. 18 PsO PowerBI Dashboard (IQVIA Midas data). 19 Pinter A, Green LJ, Selmer J, Praestegaard M, Gold LS, Augustin M; trial investigator group. A pooled analysis of randomized, controlled, phase 3 trials investigating the efficacy and safety of a novel, fixed dose calcipotriene and betamethasone dipropionate cream for the topical treatment of plaque psoriasis. J Eur Acad Dermatol Venereol. 2022 Feb;36(2):228–236. doi: 10.1111/jdv.17734. 20 Præstegaard M, Vestbjerg B, Selmer J, Holm-Larsen T. Phase 3 trial demonstrates superior patient treatment convenience of MC2-01 calcipotriene plus betamethasone dipropionate cream compared to current topical suspension. J of Skin. 2020;4(5):s62. doi: 10.25251/skin.4.supp.61. 21 Stein Gold L, Green LJ, Dhawan S, Vestbjerg B, Praestegaard M, Selmer J. A phase 3, randomized trial demonstrating the improved efficacy and patient acceptability of fixed dose calcipotriene and betamethasone dipropionate cream. J Drugs Dermatol. 2021 Apr;20(4):420-425. doi:10.36849/ JDD.5653. PMID: 33852251. 22 Bewley A, et al. An anchored matching-adjusted indirect comparison of fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BDP) cream versus Cal/BDP foam for the treatment of psoriasis. J Dermatolog Treat. 2022 33 (8): 3191-3198. 23 PsO PowerBI Dashboard (IQVIA Midas data). 24 Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007 Sep;33(9):1099-101. doi: 10.1111/j.1524-4725.2007.33224.x. 25 Wilmer EN, Gustafson CJ, Ahn CS, Davis SA, Feldman SR, Huang WW. Most common dermatologic conditions encountered by dermatologists and nondermatologists. Cutis. 2014 Dec;94(6):285-92. 26 AK PowerBI Dashboard (IQVIA Midas data). 27 Tan JKL, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015 Jul;172 Suppl 1:3-12. doi: 10.1111/bjd.13462. PMID: 25597339. 28 Wolkenstein P, Machovcová A, Szepietowski JC, Tennstedt D, Veraldi S, Delarue A. Acne prevalence and associations with lifestyle: a cross-sectional online survey of adolescents/young adults in 7 European countries. J Eur Acad Dermatol Venereol. 2018 Feb;32(2):298-306. 29 Dalgard F, Gieler U, Holm JØ, Bjertness E, Hauser S. Self-esteem and body satisfaction among late adolescents with acne: results from a population survey. J Am Acad Dermatol. 2008 Nov;59(5):746-51. doi: 10.1016/j.jaad.2008.07.013. PMID: 19119094. 30 Maskan Bermudez N, Rodríguez-Tamez G, Perez S, Tosti A. Onychomycosis: Old and New. Journal of Fungi. 2023; 9(5):559. https://doi.org/10.3390/jof9050559. 31 Sigurgeirsson B, Baran R. The prevalence of onychomycosis in the global population: a literature study. J Eur Acad Dermatol Venereol. 2014 Nov;28(11):1480-91. doi: 10.1111/jdv.12323. Epub 2013 Nov 28. PMID: 24283696. 32 Ciclopoli® (Ciclopirox) SmPC. 33 Monti D, Saccomani L, Chetoni P, Burgalassi S, Saettone MF, Mailland F. In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer. Drug Dev Ind Pharm. 2005 Jan;31(1):11-7. doi: 10.1081/ddc-43935. 34 Sparavigna M, Setaro M, Frisenda L. Physical and microbiological properties of a new nail protective medical device. J Plastic Dermatol. 2008;4(1):5-12. 35 Monti D, Saccomani L, Chetoni P, Burgalassi S, Senesi S, Ghelardi E, Mailland F. Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding antimycotic activity. Br J Dermatol. 2010 Feb;162(2):311-7. doi: 10.1111/j.1365-2133.2009.09504.x. 36 Iorizzo M, Hartmane I, Derveniece A, Mikazans I. Ciclopirox 8% HPCH nail lacquer in the treatment of mild-to-moderate onychomycosis: A randomized, amorolfine controlled study using a blinded evaluator. Skin Appendage Disord. 2016 Feb;1(3):134-40. doi: 10.1159/000441569. Sociedad Española de Neurología. Cada año se diagnostican unos 10 millones de nuevos casos de Alzheimer en el mundo. Available from: https://www.sen.es/saladeprensa/pdf/Link347.pdf 37 Sociedad Española de Neurología. Cada año se diagnostican unos 10 millones de nuevos casos de Alzheimer en el mundo. Available from: https://www.sen.es/saladeprensa/pdf/Link347.pdf. Atopic dermatitis Atopic dermatitis (AD), or atopic eczema, is a non-contagious, chronic inflammatory disease characterized by recurrent skin inflammation, often associated with intense pruritus or itching. Beyond physical symptoms such as dryness, itchiness, redness, and inflammation, this condition significantly impacts emotional wellbeing and disrupts the academic, social, and professional lives of those affected.1 With an estimated prevalence of up to 4.4% among adults in the EU, the incidence of AD has increased in recent decades, with approximately 20-30% of patients having moderate-to-severe disease.2,3,4 EBGLYSS® (lebrikizumab) EBGLYSS® (lebrikizumab) is a biologic treatment specially developed to target the protein IL-13 with high precision and affinity, selectively inhibiting its downstream signalling pathway with high potency.5,6,7,8 In November 2023, the European Commission (EC) approved EBGLYSS® (lebrikizumab) for the treatment of adult and adolescent patients (12 years and older with a body weight of at least 40 kg) with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy. The approval is based on the results from the pivotal phase III studies ADvocate 1, ADvocate 2, evaluating lebrikizumab as monotherapy, and ADhere, assessing lebrikizumab in combination with topical corticosteroids (TCS), in adult and adolescent patients with moderate-to-severe atopic dermatitis. During these studies, lebrikizumab demonstrated clinical efficacy in monotherapy at week 16,9 reducing disease extent and severity by at least 75% in nearly 6 out of 10 patients, while in combination with topical corticosteroids (TCS),10 these results were achieved in nearly 7 out of 10 patients. In addition, almost 80% of patients who responded to treatment at week 16* and continued treatment both in monotherapy and in combination with TCS for two years, experienced sustained skin clearing, itch relief, and reduced disease severity with monthly maintenance dosing.11 The phase III clinical development programme also assessed lebrikizumab’s safety. Findings show most adverse events were mild or moderate and did not lead to discontinuation of treatment. The most frequent adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eyes.12 Lebrikizumab represents a significant step forward for patients with moderate-to-severe AD not controlled with topical therapy. This is thanks to its selective mechanism of action,6 proven short and long-term efficacy and safety demonstrated for up to 2 years,9,10,13 and a monthly maintenance dosing for all patients.11 Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in Europe, while Eli Lilly and Company has exclusive rights for the further development and commercialization of the product in the United States and the rest of the world (except Europe). In December 2023, the commercial launch began in Germany, with expansion to more European countries planned for 2024. *Treatment responders were defined as patients who achieved a 75% reduction in the Eczema Area and Severity Index from baseline (EASI-75) or an EASI 0 or 1 ("cleared" or "almost cleared") with at least a 2-point improvement and no need for rescue medication at week 16. Cordran® Tape (flurandrenolide) Cordran® Tape (flurandrenolide) is a topical corticosteroid treatment prescribed to reduce the itching, redness and swelling which may occur with corticosteroid-responsive dermatosis, including AD. Cordran® Tape is primarily effective because of its anti-inflammatory, antipruritic and vasoconstrictive actions. Almirall commercializes this product in the United States and Japan. In the United States, Cordran® Tape (flurandrenolide) is commercialized as the only corticosteroid available in a tape form. Immune inflammatory diseases Psoriasis Psoriasis, impacting an estimated 60 million individuals globally,14 is a chronic, autoimmune skin disorder characterized by inflammation. The condition manifests through reddish, scaly patches, frequently appearing on the elbows, knees, scalp, and lower back but it can also affect other skin areas, including nails. Physical symptoms of psoriasis are often painful and disfiguring, having a broad impact on patients' lives and mental health, with clinical depression diagnosed in one out of every ten psoriasis patients.15 Such profound effects on the quality of life necessitate diverse treatment strategies. Almirall, unique among European biopharmaceutical companies, addresses this need by offering a comprehensive range of treatments, encompassing products from topical solutions to oral systemics and biologics, catering to the full spectrum of the condition. Ilumetri® (tildrakizumab) Ilumetri® (tildrakizumab) is a humanized monoclonal antibody that targets the p19 subunit of interleukin-23 (IL-23) and inhibits the release of proinflammatory cytokines and chemokines with limited impact on the rest of the immune system. It is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. At the 32nd EADV congress in 2023, Almirall presented the results from POSITIVE, a Real-World Evidence study that assessed the wellbeing of people suffering from psoriasis using the WHO-5 questionnaire. The study found that psoriasis significantly impacts wellbeing, similar to the effects caused by other diseases such as breast cancer.16,17 The first interim results from the study at 28 weeks showed significant improvement in the wellbeing of psoriasis patients treated with tildrakizumab, reaching levels comparable to the average wellbeing of the European population. The study also reinforced the effectiveness and safety of tildrakizumab in daily clinical practice. Ilumetri® had a strong sales performance in 2023, achieving around 34% sales increase year-on-year and helping more than 17,000 patients during that year.18 Growth was boosted by new country launches in Norway, Iceland, Sweden, and Finland; plus, the increase of sales in Germany, which accounts for almost half of total product sales. This growth trend is expected to continue throughout 2024. Wynzora® cream (calcipotriol/betamethasone) Wynzora® cream is a once-daily topical treatment for adults with mild-to-moderate plaque psoriasis, including the scalp.19 Wynzora® cream is based on PAD Technology, which formulates an aqueous cream that is less greasy than a CAL/BDP gel.20 It offers high efficacy, a favourable safety profile with a fast onset of action within one week, and improved patient acceptability compared to CAL/BDP gel.20,21 An indirect comparison revealed equivalent efficacy and quality of life improvement, with even higher patient satisfaction than CAL/BDP foam.22 Wynzora® is authorized in France, the UK, Spain, the Czech Republic, Denmark, Norway, Sweden, Finland, Germany, Portugal, Italy, Ire-land, the Netherlands, and Austria under a dif-ferent tradename: Winxory®. Wynzora® helped more than 170,000 patients during 2023.23 Skilarence® (dimethyl fumarate) Skilarence® (dimethyl fumarate) is an oral medicine for treating adults with moderate to severe plaque psoriasis. It is indicated as a first-line treatment and long-term maintenance therapy. Notably, it is also the first and only European Commission-approved fumaric acid ester (FAE) for the treatment of adults with psoriasis in need of systemic medicinal therapy. Commercialized in 18 European countries and South Korea, this treatment is widely accessible and has proven highly successful. Immune inflammatory diseases Actinic keratosis Actinic keratosis (AK), characterized by rough, scaly skin lesions, is a common diagnosis in dermatology. These lesions typically develop on sun-exposed areas of the skin, such as the face, ears, lips, balding scalp, forearms, backs of hands, and lower legs. As a chronic and recurrent condition, AK increases the risk of suffering squamous cell carcinoma (SCC), which is the second most common type of skin cancer.24 Early detection and treatment of AK lesions are crucial in mitigating the risk of developing SCC in due course. Klisyri® (tirbanibulin) Klisyri® (tirbanibulin) is an innovative topical treatment with a selective antiproliferative mechanism of action. It represents a significant step forward in the treatment of AK due to its short treatment protocol (a once-daily application for 5 consecutive days), proven efficacy, safety profile, and good tolerability results. Klisyri® received a recommendation in the German AK treatment guidelines, published in 2023. In the United States, where AK is the second most common dermatologist diagnosis,25 Klisyri® received a strong recommendation in the Journal of the American Academy of Dermatology for a high certainty of evidence. Also in the US, Klisyri® phase l and phase lll studies were completed in 2023 to apply for its use in large areas of the skin (100 cm2). Consequently, a request to extend the area of treatment has been submitted to the FDA, with approval expected mid-2024. Klisyri® is already commercialized in the United States, Germany, the United Kingdom, Switzerland, Austria, the Netherlands, Italy, Spain, Ireland, Denmark, and Belgium. Since its launch, around 400,000 patients have benefited from the treatment with Klisyri®.26 Actikerall® (fluorouracil/salicylic acid) Actikerall® is a lesion-directed topical for the treatment of hyperkeratotic actinic keratosis. Easy to use (applied locally once daily), it is a highly effective treatment for mild-to-moderate AK. The active ingredients combine 0.5% fluorouracil, a cytostatic agent that inhibits cell growth, and 10% salicylic acid. Solaraze® (diclofenac sodium) A nonsteroidal anti-inflammatory topical treatment, its active ingredients are diclofenac (3%) and hyaluronic acid (10%). Used to treat AK lesions and adjacent sun-damaged skin, it reduces angiogenesis and cellular proliferation. Known for its high efficacy and good tolerability profile in long-term treatment, it is especially suitable for patients who have received organ transplants. Solaraze® has now been marketed in over 10 European countries, as well as Australia and is the leader in Spain and Italy with a market share above 50%. Non-melanoma skin cancer Acne Acne, one of the most prevalent inflammatory dermatoses treated globally, affects an estimated 9.4% of the world population.27 This condition, causing inflammatory and non-inflammatory lesions, mainly affects the face, upper arms, trunk, and back. While more common in adolescents and young adults, especially males, it is not limited to these age groups. Studies suggest that 35%-90% of adolescents experience acne.28 Its complex pathophysiology involves a combination of factors: hormonally induced sebum production, abnormal keratinization within the pilosebaceous duct, and an immune response. Its impact goes beyond physical symptoms, increasing depressive symptoms and diminishing self-confidence and self-worth.29 Seysara® (sarecycline) Seysara® (sarecycline) is a first-in-class tetracycline-derived oral antibiotic for the treatment of inflammatory lesions of moderate-to-severe non-nodular acne vulgaris. At the end of 2023, Seysara® (sarecycline) was the most prescribed branded oral antibiotic for treating acne in the United States. In addition to its presence in the United States market, Almirall’s product strategy includes future expansion to China. The phase III clinical trial conducted in this country for sarecycline met primary and key secondary endpoints, and the NDA submission to the Chinese Health Authorities was completed in September 2023. Other skin diseases Onychomycosis Onychomycosis, or nail fungus, is the leading cause of nail infections, responsible for nearly half of all nail disorder consultations.30 More common in males and known to increase with age in both genders,28,31 it is initially characterized by white, yellow, or black spots at the nail's edge or base near the cuticle, encompassing the entire nail as it progresses. This contagious disease can infect other nails or people through contact with contaminated surfaces, causing significant mental discomfort due to its persistent nature. Ciclopoli® nail lacquer franchise (ciclopirox) Ciclopoli® is a once-daily topical treatment indicated for mild-to-moderate fungal infections of the nails.32 It is a water-soluble nail lacquer that contains the active ingredient, ciclopirox 8%, and hydroxypropyl chitosan (HCPH), a technology that effectively delivers ciclopirox straight to the affected part of the nail.33,34 This formulation allows rapid penetration of the active ingredient35 into the nail and does not require nail filing, thereby greatly improving patient compliance.36 Ciclopoli® is marketed worldwide under dif-ferent tradenames: Ony-Tec®, Kitonail®, Nio-germox®, Niogermos®, Myconail®, Polinail®, Privex®, Rejuvenail® and Fulcare®. In 2023, the Ciclopoli® franchise remained one of Almirall’s flagships in our dermatology portfolio, with approximately €45 MM in sales. Other skin diseases Our mission is to help improve patients' lives through the products and technologies of our portfolio, addressing key needs of our patients across a range of therapy areas. While we aim to lead in dermatology, our diverse portfolio also supports patients in other disease areas, enabling us to address healthcare needs beyond dermatology. Sativex® franchise (THC:CBD) This product is a cannabis-based medicine containing tetrahydrocannabinol (THC) and cannabidiol (CBD). It is indicated for the treatment of resistant multiple sclerosis spasticity and associated cramps, pain, mobility impairment, bladder dysfunction, and sleep disorders. Sativex® is an oral sublingual spray. Crestor® and Provisacor® (rosuvastatin) Both trademarks contain the active ingredient rosuvastatin, a statin medication that works by reducing the amount of cholesterol made by the liver and therefore can help to reduce the risk of heart attacks or strokes. Both brands are effective treatments for high blood cholesterol, LDL cholesterol, and triglyceride levels, often associated with low HDL cholesterol. Almax® (almagate) Almax®, effective for heartburn and gastric acidity in adults and children over 12, addresses symptoms affecting over 40% of the population. Its active ingredient, almagate, neutralizes stomach acid for quick relief. Available in chewable tablets, powder, and liquid suspension. Ebastel® franchise (ebastine) Marketed in over 30 countries worldwide, the ebastine family of antihistamines (Ebastel®, Kestin®, Kestine®, Evastel®, Estivan®) is a once-daily, non-sedating, selective, and long-acting treatment for allergic rhinitis (seasonal and perennial), chronic idiopathic urticaria, and allergy-related conjunctivitis. Benefits of this H1 receptor antagonist include good symptom relief, a positive safety and tolerability profile, lack of drowsiness, and all-day coverage. Efficib® (sitagliptin/metformin) and Tesavel® (sitagliptin) Efficib® and Tesavel® are indicated as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on metformin alone or those already being treated with the combination of sitagliptin and metformin. They are also indicated in combination with a sulphonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea. Prometax® (rivastigmine patches) Prometax® is a daily transdermal medicated patch used to alleviate Alzheimer's-related dementia symptoms. This medication helps patients enjoy their daily lives without having to worry about regular medication; it is also highly beneficial for individuals who struggle with swallowing. Acquired by Almirall in 2023, it's marketed in Spain, where Alzheimer's is a leading dementia form with over 800,000 cases, increasing annually due to an ageing population. Physiorelax® franchise (Helenalin2) Physiorelax® is a brand of topical products of natural origin, that massage the muscles and ligaments. The main ingredient is Helenalin2, which combines arnica, hypericum, harpagophytum and calendula. The brand portfolio includes a variety of products like Forte, Heat and Cold effects, and a CBD-based cream, catering to diverse user needs. Almirall acquired global rights in 2023, it is marketed in Spain. Key products in other areas