IL-23p19

Submission is supported by data from the Phase 3 QUASAR program, which showed a significantly greater percentage of patients with moderately to severely active ulcerative colitis who received TREMFYA® achieved clinical remission at Week 44 compared with placebo SPRING HOUSE, Pa., March 11, 2024 /PRNewswire/ -- Johnson & Johnson today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of TREMFYA® (guselkumab) for treatment of adults with moderately to severely active ulcerative colitis (UC). The submission is based on results from the Phase 3 QUASAR program evaluating the efficacy and safety of TREMFYA® in the treatment of individuals living with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, prior biologics and/or JAK inhibitors.1 The data show statistically significant and clinically meaningful improvements in symptoms, patient-reported outcomes such as fatigue and measures of disease activity including high bar endpoints such as endoscopic and histologic remission.2,3 The safety results were consistent with the known safety profile of TREMFYA® in approved indications.2,3,a "Despite advances in therapy, many people living with ulcerative colitis still experience inadequate response to or do not tolerate existing therapies," said David Lee, MD, PhD, Global Therapeutic Area Head Immunology. "TREMFYA has the potential to be a new treatment option for patients. We look forward to working with the FDA in review of this application and remain focused on developing new therapies for those living with chronic autoimmune conditions, such as ulcerative colitis, who are experiencing persistent and debilitating symptoms." TREMFYA® is a dual-acting IL-23i that blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23.4 IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including UC.5 TREMFYA® was first approved in the U.S. in July 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis and was subsequently also approved for adults with active psoriatic arthritis in July, 2020.4 Clinical data from the Phase 3 QUASAR induction study through 12 weeks were presented at the 2023 Digestive Disease Week (DDW) Annual Meeting2 and results from the Phase 3 QUASAR maintenance study through 44 weeks will be presented at an upcoming medical meeting. Editor's Notes: a. TREMFYA® is not approved to treat UC. ABOUT THE QUASAR STUDY ( NCT04033445 ) QUASAR is a randomized, double-blind, placebo-controlled, parallel group, multicenter, seamless Phase 2b/3 program designed to evaluate the efficacy and safety of TREMFYA®, a selective IL-23 inhibitor, in adult patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics and/or JAK inhibitors (i.e., tumor necrosis factor-alpha antagonists, vedolizumab, or tofacitinib).1 QUASAR included a Phase 2b dose-ranging induction study, a confirmatory Phase 3 induction study, and a Phase 3 maintenance study. Efficacy, safety, pharmacokinetics, immunogenicity, and biomarkers are assessed at specified time points.1 ABOUT ULCERATIVE COLITIS Ulcerative colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus.6 It is the result of the immune system's overactive response.6 Symptoms vary, but may include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss and fatigue.6 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA® is the first approved fully-human, dual-acting monoclonal antibody that blocks IL-23 by binding to the p19 subunit of IL-23 and binding to CD64, a receptor on cells that produce IL-23.4 IL-23 is an important driver of the pathogenesis of inflammatory diseases.5 Findings for dual acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known.7,8,9,10 TREMFYA® is approved in the U.S.,4 Canada,11 Japan12 and a number of other countries for the treatment of adults with moderate to severe plaque psoriasis (PsO) who are candidates for injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light) and for the treatment of adult patients with active psoriatic arthritis ( PsA).4 It is also approved in the EU for the treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy and for the treatment of active PsA in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.13 Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA®. IMPORTANT SAFETY INFORMATION3 What is the most important information I should know about TREMFYA® (guselkumab)? TREMFYA® is a prescription medicine that may cause serious side effects, including: Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: fainting, dizziness, feeling lightheaded (low blood pressure) swelling of your face, eyelids, lips, mouth, tongue or throat trouble breathing or throat tightness chest tightness skin rash, hives itching Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: fever, sweats, or chills muscle aches weight loss cough warm, red, or painful skin or sores on your body different from your psoriasis diarrhea or stomach pain shortness of breath blood in your phlegm (mucus) burning when you urinate or urinating more often than normal Do not use TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®. Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section "What is the most important information I should know about TREMFYA®?" have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®. are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of TREMFYA®? TREMFYA® may cause serious side effects. See "What is the most important information I should know about TREMFYA®?" The most common side effects of TREMFYA® include: upper respiratory infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, and bronchitis. These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects. Use TREMFYA® exactly as your healthcare provider tells you to use it. Please read the full Prescribing Information , including Medication Guide for TREMFYA®, and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1– 800– FDA– 1088. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 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 or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are a Johnson & Johnson companies. National Institutes of Health: Clinicaltrials.gov. A study of guselkumab in participants with moderately to severely active ulcerative colitis (QUASAR). Identifier: NCT04033445. Available at: . Accessed February 2024. Allegretti, J, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 QUASAR induction study. Presented at Digestive Disease Week, May 6-9. Peyrin-Biroulet L, et al. Guselkumab in patients with moderately to severely active ulcerative colitis: QUASAR Phase 2b induction study. Gastroenterology. 2023 Dec;165(6):1443-1457. doi: 10.1053/j.gastro.2023.08.038. Epub 2023 Sep 1. PMID: 37659673. US Food and Drug Administration. TREMFYA® Prescribing Information. Available at: . Accessed February 2024. Schinocca, C. et al. Role of the IL-23/IL-17 pathway in rheumatic diseases: an overview. Frontiers in immunology. 2021 Feb 22;12:321. . Crohn's & Colitis Foundation. What is ulcerative colitis? Available at: . Accessed February 2024. Mehta H, et al. Differential Changes in inflammatory mononuclear phagocyte and T-Cell profiles within psoriatic skin during treatment with guselkumab vs. secukinumab. J Invest Dermatol 2021;141(7):1707-1718. Available at: . Accessed February 2024. Wang Y, et al. Monocytes/Macrophages play a pathogenic role in IL-23 mediated psoriasis-like skin inflammation. Sci Rep. 2019;9(1):5310. Available at: . Accessed February 2024. Matt P, et al. Up-regulation of CD64-expressing monocytes with impaired FcγR function reflects disease activity in polyarticular psoriatic arthritis. Scand J Rheumatol 2015; 44(6):464-473. Available at: . Accessed February 2024. McGonagle D, et al. Guselkumab, an IL-23p19 subunit–specific monoclonal antibody, binds CD64+ myeloid cells and potently neutralises IL-23 produced from the same cells. Presented at EULAR 2023, May 31-June 3. The Canadian Agency for Drugs & Technologies in Health. TREMFYA Prescribing Information. Available at: . Accessed February 2024. Japan Pharmaceuticals and Medical Devices Agency. Tremfya Report on the Deliberation Results. Available at: . Accessed February 2024. European Commission: Tremfya (guselkumab). Available at: . Accessed February 2024. SOURCE Johnson & Johnson

Findings show that seborrheic dermatitis is a unique inflammatory skin disease with its own molecular signatureSuggests skin barrier disruption in seborrheic dermatitis is distinct with its own disease-specific pattern SAN DIEGO, Calif., March 09, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, highlights new research that, for the first time, reveals the gene expression profile of seborrheic dermatitis. The Arcutis sponsored research from The Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai was presented in a scientific session at the American Academy of Dermatology (AAD) annual meeting (San Diego, CA, March 8 – 12) and answers key questions on the immune response and associated skin barrier disruption of seborrheic dermatitis. “Our research group has had a longstanding interest in defining the immunological pathways that underlie many inflammatory skin diseases, such as atopic dermatitis and psoriasis, shaping our understanding of these diseases and leading to new treatments,” said Emma Guttman-Yassky, MD, PhD, the Waldman Professor of Dermatology and Immunology and Health System Chair of The Department of Dermatology, and Director of the Laboratory for Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai. “We are excited to have successfully employed noninvasive tape-stripping techniques developed from studying these diseases to study an understudied and undertreated inflammatory skin disease, seborrheic dermatitis. These findings will help establish the groundwork for greater understanding of this very common condition.” “The pathophysiology of seborrheic dermatitis has been poorly understood. We sought to understand the gene expression patterns in seborrheic dermatitis in order to determine if this profile is distinct from or similar to other immune-mediated skin conditions,” said Benjamin Ungar, MD, director of the Alopecia Center of Excellence and director of the Rosacea & Seborrheic Dermatitis Clinic at Mount Sinai Health System. “Our data reveal that seborrheic dermatitis has a distinct immunological molecular profile. In addition, the skin barrier disruption observed in seborrheic dermatitis has unique molecular underpinnings, primarily in the tight junction of the epithelial skin cells and lipid metabolism pathways. These findings are the first to characterize the molecular profile of seborrheic dermatitis, and they will play an important role in advancing our understanding of this common and under-treated condition.” Dr. Ungar is also an assistant professor of Dermatology at the Icahn School of Medicine at Mount Sinai. The data reported at AAD are from an observational study in which tape-strips were collected from facial lesions from 27 untreated patients with seborrheic dermatitis (Investigator’s Global Assessment score mild [IGA 2, n=400], moderate [IGA 3, n=19], severe [IGA 4, n=4]) and the facial skin of 18 healthy controls and analyzed with RNA sequencing (RNA-seq). Tape-strips are a non-invasive alternative to biopsy for transcriptome analysis and expression profiling. These data demonstrate that seborrheic dermatitis is an immune disease with a uniquely polarized profile distinct from atopic dermatitis and plaque psoriasis. In addition, skin barrier disruption is suggested by a downregulation of tight junction and lipid metabolism genes. Specific findings include: 1,374 differentially expressed genes (DEGs) were identified between seborrheic dermatitis and healthy controls (674 with increased expression, 700 with decreased expression).Strong and significant upregulation of Th17-related (i.e. IL23A, PI3, LL37) and Th22-related (i.e. IL22, S100A8, S100A12) pathways were detected in seborrheic dermatitis compared with controls.Seborrheic dermatitis also showed significant Th1 activation (OASL, STAT1, CXCL9) compared with controls.There was significant downregulation of skin barrier markers (CLDN1/8, FA2H, ELOVL3) in seborrheic dermatitis compared with controls.IGA positively correlated with immune markers, including Th1/IFNG, Th17/IL17A, and Th22/IL22 [r>0.3; P<0.1 for all] and negatively correlated with skin barrier markers (SMPD4, MGLL, PLA2G15 [r≤-0.38; P<0.05]). “Despite the high prevalence of seborrheic dermatitis, there has been little dedicated clinical or basic research into the underlying cause of this chronic, inflammatory skin disease for decades. Through this collaborative research effort, we have begun to shed some light on the pathways involved in the immune response and demonstrate that seborrheic dermatitis is clearly distinct from psoriasis or atopic dermatitis, which may help explain the clinical expression of the disease, and ultimately provide important insights into its management,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer, Arcutis. “We are committed to advancing the scientific understanding of this disease through additional research and collaboration with the larger dermatology research and clinical community.” Mount Sinai has received grants from Arcutis for research conducted by Dr. Ungar and Dr. Guttman. In addition, Dr. Ungar and Dr. Guttman have served as paid consultants for Arcutis. About Seborrheic DermatitisSeborrheic dermatitis affects up to 10 million people in the United States, and is a common, chronic, and recurrent inflammatory skin disease that causes red patches covered with large, greasy, flaking yellow-gray scales, and persistent itch. Seborrheic dermatitis occurs most often in areas of the body with oil-producing (sebaceous) glands, including the scalp, face (especially on the nose, eyebrows, ears, and eyelids), upper chest, and back. About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio including two FDA approved products that harness our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis’ dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, atopic dermatitis, and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, and X. Forward-Looking StatementsArcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the genetic profile and cause of seborrheic dermatitis. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, the impact of competition and other important factors discussed in the "Risk Factors" section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 27, 2024, as well as any subsequent filings with the SEC. You should not place undue reliance on any forward-looking statements in this press release. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts:MediaAmanda Sheldon, Head of Corporate Communicationsasheldon@arcutis.com InvestorsLatha Vairavan, Vice President, Finance and Investor Relationslvairavan@arcutis.comDerek ColeInvestor Relations Advisory Solutionsderek.cole@iradvisory.com

Almirall achieves Net Sales growth of 6.4%, driven by strong European dermatology performance Almirall's European Dermatology business continued to be the driving force behind Almirall's strong performance in the first nine months of 2023, with a growth rate of 15.9% underpinned by the success of Ilumetri® and other recently launched products Good performance of Key products in Europe: strong year-on-year growth of Ilumetri® (psoriasis) across geographies; Wynzora® (psoriasis) sales gaining traction, reinforced by recent country launches; and Klisyri® (actinic keratosis) rollout driving its favourable uptake Lebrikizumab (EBGLYSS®) received positive CHMP opinion for marketing authorization in patients with moderate-to-severe atopic dermatitis; EU approval is usually expected within two months of the CHMP's positive opinion. Pipeline development: based on the large field study data of tirbanibulin, the company submitted a supplementary New Drug Application (sNDA) in August 2023 and expects approval and a subsequent launch in H2 2024 The additional funds obtained from the capital increase executed in June allowed Almirall to take strategic steps to expand its capabilities. In the third quarter Almirall completed the acquisition of the rights of Prometax® in Spain, highly synergetic with Almirall’s existing neurology business in Spain. In parallel, the company continues to explore other opportunities for early and mid-stage assets Almirall is on track to meet mid-single net sales digit growth (vs. initial low- to mid-single guidance) and continues to expect total EBITDA between €165 MM - €180 MM BARCELONA, Spain--(BUSINESS WIRE)-- Almirall, S.A. (ALM), the global biopharmaceutical company based in Barcelona, has announced its 9M 2023. Financial highlights (€ rounded million) 9M 2023 9M 2022 Variation Net Sales 674.6 633.8 6.4% Core EBITDA 137.1 134.0 2.3% Total EBITDA 138.2 146.4 (5.6%) Net Income 13.6 10.9 24.8% Normalized Net Income 14.4 34.5 (58.3%) Summary of results Net Sales reached €674.6 MM, a +6.4% year-on-year increase driven by good performance of the dermatology portfolio in Europe. Total EBITDA was €138.2 MM, consistent with expectations and reflecting the lower contribution from Other Income due to Astra Zeneca / Covis milestones compared to 9M 2022. SG&A (Selling, General and Administrative) investment was €316.7 MM, 2.5% higher than last year, as expected. This increase reflects the company's ongoing investments in the premarketing ramp-up for lebrikizumab, as well as its investments in the recent launches of Wynzora® and Klisyri® in the US and EU, and the rollout of Ilumetri®. Gross Margin of 64.9% was in line with expectations and reflects the impact of high input costs and inflation affecting some material purchases. R&D investment was €78.4 MM, reaching 11.6% of Net Sales. R&D expenses are expected to normalize for the full year in the range of 12% of Net Sales. Almirall finished the first 9 months of 2023 with a favourable balance sheet and solid liquidity position at 0.2x Net Debt to EBITDA. “Almirall has delivered a consistently strong operational performance throughout the first nine months of 2023, and we are pleased to modestly upgrade our Net Sales guidance for the year. As we gear up for the lebrikizumab launch, we're embarking on a transformative journey for our company. The expected EMA approval, following the positive CHMP opinion, is just around the corner. We maintain confidence in the positive trajectory of our growth drivers as we continue to support their success. Moreover, we have strategically utilized the additional capital from our recent capital increase to strengthen our portfolio, while we continue to explore other opportunities to enhance our R&D portfolio. This reflects our commitment to advancing innovation in dermatology and positions us favourably to realize our ambition of becoming a leading dermatology company, paving the way in medical dermatology by providing innovative solutions that profoundly impact patients' lives.” Carlos Gallardo Piqué, Chairman and CEO Growth Drivers Performance Psoriasis Ilumetri® (tildrakizumab), an anti-IL-23 biologic for moderate-to-severe plaque psoriasis, has continued its strong performance in 9M 2023, posting 38% growth compared to 9M 2022 and achieving Net Sales of €42 MM in Q3 in Europe. Almirall expects Q4 to resume growth momentum and anticipates that the absolute growth for 2023 will be comparable to that of 2022. Penetration of the European market continues to be on track. Furthermore, Germany accounted for almost half of the sales, while other European countries contributed more than half, demonstrating the good traction of the product in other key markets. Almirall unveiled new data at the European Association of Dermatology and Venereology Congress 2023 demonstrating for the first time that tildrakizumab improved patients’ wellbeing in moderate-to-severe psoriasis, achieving levels similar to the general population after 16 weeks and which was maintained up to week 28.1 Additionally, tildrakizumab demonstrated its effectiveness, improving patients’ health-related quality of life (HRQoL), with high rates of treatment satisfaction in patients with moderate-to-severe plaque psoriasis after 28 weeks in a real-world setting,2 with no new safety signals and a reassuring safety pro >3 consistent with previous randomized clinical trials (RCT) and real-world studies.4,5 The new evidence on the TRIBUTE study demonstrated that tildrakizumab improved other important patient-reported outcomes (PROs) such as sleep quality, which is highly correlated with itch, pain, quality of life, and work productivity and not with PASI.6,7 The results also revealed that tildrakizumab demonstrated similar efficacy and safety regardless of the baseline characteristics of the patients.8,9 Almirall also reported results from the TILOT study that demonstrated sustained efficacy and safety of tildrakizumab over 2 years in patients with moderate-to-severe plaque psoriasis in routine clinical practice including sensitive areas and improvements of itch.10 This was reflected in significant improvements in all measured parameters, including treatment satisfaction and quality of life.11 Additionally, Wynzora® cream, a once-daily aqueous cream with a fixed combination of calcipotriene and betamethasone diproprionate (CAL/BDP), indicated for the topical treatment of mild to moderate psoriasis vulgaris in adults, achieved sales of €11.8 MM in 9M 2023 vs €4.5 MM in 9M 2022. The growth of the product was primarily driven by recent country launches and the continuous expansion in key countries. The cream has maintained strong performance throughout the year. Notably, both healthcare professionals and patients have expressed positive feedback about the product, emphasizing its efficacy, quick absorption, and non-sticky feel texture. The company is confident that it has potential for significant growth in markets where the product has been already launched, such as Germany, Spain, the UK, Denmark, the Netherlands, Italy and Austria, as well as in additional EU countries in the upcoming quarters. Wynzora® is commercialized in Austria under a different tradename: Winxory. Actinic keratosis (AK) Klisyri® (tirbanibulin) ointment for actinic keratosis (AK) on the face or scalp achieved net sales of €14.4 million in Europe and the United States during the first nine months of 2023, representing a 57% increase compared to the €9.2 MM recorded in the same period in 2022. Klisyri® showed robust performance in key markets and its presence in the EU continues to grow. The product has experienced solid adoption in key countries where it has been launched. In the US, Almirall continues to focus on driving demand by differentiating Klisyri® from what is already available on the market based on efficacy, tolerability, and convenience. As a result, Klisyri® usage is associated with high overall patient satisfaction and a strong willingness to repeat treatment, as reported by dermatologists and patients.12 Prometax® In September 2023, Almirall announced the acquisition of exclusive rights to Prometax® in Spain. The product is a transdermal patch with rivastigmine to treat Alzheimer’s Disease, increasing the level of the neurotransmitter acetylcholine which helps reduce the symptoms of Alzheimer’s. The product is highly synergetic with Almirall’s existing neurology business in Spain. The transaction was agreed based on an upfront payment of €45 MM and potential milestones of up to €15 MM. Late-stage pipeline with promising potential Atopic dermatitis (AD) In the third quarter of 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending the marketing authorization of lebrikizumab (EBGLYSS) 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 positive CHMP opinion is now being reviewed by the European Commission (EC). The approval in the European Union is expected in November and its launch in the first European country could take place soon after. The company expects regulatory decisions for lebrikizumab in moderate-to-severe AD in additional European markets. Regarding the UK, approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) is expected by the end of the year, following the EC's Reliance Procedure. In Switzerland, Almirall submitted the MAA in June 2023 and approval is expected by the end of 2024. In addition to the regulatory milestone, Almirall announced several positive clinical updates on lebrikizumab. At the European Academy of Dermatology and Venereology (EADV) Congress in October, lebrikizumab showed clinical improvements in combination with topical corticosteroids (TCS) in adult and adolescent patients with moderate-to-severe AD not adequately controlled with cyclosporine or for whom cyclosporine was not medically advisable, who were assessed over 16 weeks in the Phase III ADvantage study.13 The study met the primary endpoint at Week 16. At Week 16, lebrikizumab 250mg Q2W plus TCS significantly improved signs and symptoms of AD measured by EASI75* in 68.4% of patients, while only 40.8% of patients on placebo plus TCS achieved EASI75. Consistent benefit was also seen in additional endpoints such as EASI90, IGA, or Pruritus NRS*. Additional data presented at the EADV Congress showed sustained depth of response in patients that participated in the Phase III monotherapy ADvocate 1 & 2 studies treated with lebrikizumab over 52 weeks. Deep responses, defined as total skin clearance (Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI 100) and itch relief (NRS 0,1), were achieved in 20% and 31% of patients by Week 16 respectively and were maintained or increased through Week 52.14 These results suggest that lebrikizumab treatment can potentially allow patients and healthcare providers to elevate their expected treatment goals in AD beyond EASI75 and NRS 0/1 response. New data on this biologic were also presented at the 43rd Annual Fall Clinical Dermatology Conference this quarter. The long-term extension study ADjoin showed patients with moderate-to-severe AD who continued treatment with lebrikizumab for up to two years experienced sustained skin clearance, itch relief and reduced disease severity with monthly maintenance dosing.15 Nearly 80% of patients with moderate-to-severe AD maintained clear or almost-clear skin with lebrikizumab monthly maintenance dosing at two years. The data set makes Almirall confident that lebrikizumab has the potential to be a first-line biologic and may support less frequent dosing. The company is working with partner Eli Lilly on further clinical studies to maximize the value of lebrikizumab, which it believes is the best antibody targeting IL-13, the key pathogenic driver of AD. Almirall looks forward to its expected approval and launch by the end of the year, while steadily intensifying its internal efforts to be ready for a successful commercial launch. *EASI=Eczema Area and Severity Index; EASI 75=at least 75% improvement from baseline in EASI; EASI 90=at least 90% improvement from baseline in EASI; IGA=Investigator’s Global Assessment; IGA (0,1)=IGA response of clear or almost clear; NRS=numeric rating scale; Q2W=every 2 weeks; Q4W=every 4 weeks (monthly) Actinic keratosis (AK) Almirall has completed the clinical study of tirbanibulin (Klisyri®) addressing the expansion to Large Field in the US. This phase III clinical study, multi-centre, open-label, single-arm study evaluated the safety and tolerability of tirbanibulin ointment 1% applied to a field of approximately 100 cm2 on the face or balding scalp in about 100 adult patients with actinic keratosis. The administration of Klisyri was well tolerated. Based on these data Almirall submitted a supplementary NDA in August 2023 and expects approval and subsequent launch in the US in H2 2024. Autoimmune dermatological diseases The company is also building an exciting early pipeline with promising recent in-licensed assets. The company is continuing its phase I study for the anti-IL-1RAP monoclonal antibody, which has potential utility across different autoimmune skin diseases. In September 2022, Almirall announced the initiation of the phase I study evaluating the safety, pharmacokinetics, pharmacodynamics, and clinical activity of ALM27134*, a potential first-in-class fully human, high-affinity monoclonal antibody that targets IL-1RAP (interleukin-1 receptor accessory protein). Almirall in-licensed exclusive global rights from Ichnos Science in 2021 to develop and commercialize ALM27134. In addition, Almirall expects to initiate a phase I clinical study for IL-2muFc autoimmune drug candidate around the end of 2023. In 2022, Almirall entered into a licensing agreement with Simcere Pharmaceutical Group for Simcere’s IL-2 mutant fusion protein (IL-2muFc) autoimmune drug candidate, ALM223** (previously SIM0278). This molecule, developed utilising Simcere’s protein engineering platform, activates regulatory T-cells. Preclinically, ALM223 exhibits an improved PK pro the potential to restore immune balance. Under the agreement signed with Simcere Pharmaceutical Group, Almirall will be granted an exclusive right to develop and commercialise ALM223 for all indications outside the Greater China region (Mainland China, Hong Kong, Macau and Taiwan). *Previously referred to as ISB 880 ** ALM223 in licensed from Simcere. Formally referred to as SIM-0278, worldwide ex-Greater China. Bispecific antibodies In October, Almirall and EpimAb Biotherapeutics announced a license agreement for the development of bispecific antibodies for up to three undisclosed target pairs. Under the terms of this agreement, Almirall will gain a license to utilize EpimAb’s proprietary Fabs-In-Tandem Immunoglobulin (FITIg®) platform technology to generate, develop and commercialize bispecific antibodies, for which Almirall will have exclusive global rights. EpimAb Biotherapeutics shall retain all rights to the FITIg® Technology. Other indications Almirall has submitted regulatory filings under the European decentralized procedure in 2022 for efinaconazole, for the treatment of mild-to-moderate fungal infection of the nail in adults and children (aged 6 years and older). This product would reinforce Almirall’s onychomycosis franchise by complementing Ciclopoli®. The regulatory approval is expected in the second half of 2024. As for the oral antibiotic Seysara® (sarecycline), the phase III clinical study conducted in China met primary and key secondary endpoints and Almirall has submitted a dossier with the Chinese National Medical Products Administration at the end of September 2023. The regulatory approval is expected in 2024. 2023 Full Year Guidance Net sales guidance upgraded: mid-single digit net sales growth (vs. initial low- to mid-single guidance) and total EBITDA between €165 MM - €180 MM. Investor Calendar 2024 Full year 2023 Financial Results – February 19th, 2024 Q1 2024 Financial Results – 13th May 2024 H1 2024 Financial Results – 22nd July 2024 9M 2024 Financial Results – 11th November 2024 About Almirall Almirall is a global biopharmaceutical company focused on medical dermatology. We collaborate with scientists and healthcare professionals to address patients' needs through science to improve their lives. Our Noble Purpose is at the core of our work: "Transform the patients' world by helping them realize their hopes and dreams for a healthy life". We invest in differentiated and ground-breaking medical dermatology products to bring our innovative solutions to patients in need. The company, founded in 1944 and headquartered in Barcelona, is publicly traded on the Spanish Stock Exchange (ticker: ALM). Throughout its 79-year history, Almirall has focused intensely on patients' needs. Almirall has a direct presence in 21 countries and strategic agreements in over 70, with about 1,800 employees. Total revenue in 2022 was €878.5 MM. For more information, please visit almirall.com Legal warning This document includes only summary information and is not intended to be exhaustive. The facts, figures and opinions contained in this document, in addition to the historical ones, are "forward-looking statements". These statements are based on the information currently available and the best estimates and assumptions that the Company considers reasonable. These statements involve risks and uncertainties beyond the control of the Company. Therefore, actual results may differ materially from those declared by such forward-looking statements. The Company expressly waives any obligation to revise or update any forward-looking statements, goals or estimates contained in this document to reflect any changes in the assumptions, events or circumstances on which such forward-looking statements are based, unless required by the applicable law. _______________________ 1 Sommer R, et al. Patient-reported well-being using tildrakizumab in a real-world setting: 28-week interim data of the phase IV POSITIVE study. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3490. 2 Augustin M, et al. Real-world effectiveness, quality of life, and treatment satisfaction with tildrakizumab in patients with moderate-to-severe psoriasis: 28-week interim data of the phase IV POSITIVE study. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3492. 3 Mrowietz U, et al. Real-world safety of tildrakizumab in patients with moderate-to-severe psoriasis: 28-week interim data of the phase IV POSITIVE study. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3491. 4 Thaçi D, et al. Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2). Br J Dermatol. 2021 Aug;185(2):323–34. doi: 10.1111/bjd.19866. 5 Drerup KA, et al. Effective and Safe Treatment of Psoriatic Disease with the Anti-IL-23p19 Biologic Tildrakizumab: Results of a Real-World Prospective Cohort Study in Nonselected Patients. Dermatology. 2022;238:615–19. doi: 10.1159/000519924. 6 Costanzo A, et al. Tildrakizumab improves sleep quality and psoriasis-related pruritus and pain in patients with moderate-to-severe plaque psoriasis in conditions close to real clinical practice. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3122. 7 Costanzo A, et al. Tildrakizumab improves sleep quality, quality of life and work productivity in patients with moderate-to-severe plaque psoriasis in conditions close to real clinical practice. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3123. 8 Costanzo A, et al. Super responders to tildrakizumab treatment in moderate-to-severe chronic plaque psoriasis in conditions close to real clinical practice. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3121. 9 Costanzo A, et al. Tildrakizumab demonstrates high efficacy regardless of baseline characteristics in patients with moderate-to-severe chronic plaque psoriasis in conditions close to real clinical practice. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3120. 10 Tsianakas A, et al. Sustained efficacy and safety of tildrakizumab over 2 years in patients with moderate to severe plaque psoriasis in routine clinical practice: interim results in week 100 from the non-interventional, prospective, multicenter study TILOT. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3110. 11 Tsianakas A, et al. Tildrakizumab improves signs and symptoms in patients with moderate to severe plaque psoriasis in a real-world setting: a holistic approach. Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3106. 12 PROAK: Patient-reported Outcomes for Tirbanibulin Effectiveness and Safety in Actinic Keratosis. SKIN The Journal of Cutaneous Medicine 2023. 13 Warren RB, et al. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis not adequately controlled or non-eligible for cyclosporine: a placebo-controlled, randomized Phase 3. 14 Simpson E, et al. Raising the bar of efficacy in atopic dermatitis: depth of response in patients treated with lebrikizumab over 52 weeks Presented at the 32nd European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3117. 15 Guttman-Yassky E, et al. Efficacy and Safety of Lebrikizumab Is Maintained to Two Years in Patients With Moderate-to-Severe Atopic Dermatitis​. 2023 Fall Clinical Dermatology Conference. 20th October, 2023. View source version on businesswire.com: Contacts Media contact Almirall Tinkle Laura Blázquez lblazquez@tinkle.es Phone: (+34) 600 430 581 Corporate Communications Almirall Mar Ramírez mar.ramírez@almirall.com Phone: (+34) 659 614 173 Investors’ Relations Almirall Pablo Divasson del Fraile pablo.divasson@almirall.com Phone: (+34) 93 291 3087 Source: Almirall S.A. View this news release online at: