Almirall's Lebrikizumab Improves Signs and Symptoms of Moderate-to-Severe Atopic Dermatitis (AD) in Patients Inadequately Controlled With or Ineligible for Cyclosporine1

• These primary data of the ADvantage study were presented today at EADV Congress
• A total of 18 lebrikizumab abstracts were disclosed at EADV, including new data on the depth of response at Week 52 and long-term clinically meaningful response
• Lebrikizumab also demonstrated improvements in absolute response in the skin over 16 weeks in patients with moderate-to-severe AD in the ADvocate 1and2 Phase 3 trials

Almirall S.A. (BME:ALM), a global biopharmaceutical company focused on medical dermatology, today announced the presentation of new data on lebrikizumab through 18 abstracts, including two oral presentations at the European Academy of Dermatology and Venereology (EADV) Congress held in Berlin from October 11^th to 14^th. Among the new data presented, 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 3 ADvantage study (NCT05149313). The safety was consistent with the known safety profile of lebrikizumab.¹

Further data presented at the congress showed sustained depth of response in patients that participated in the Phase 3 monotherapy Advocate 1 and 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 percent of patients by Week 16 respectively and were maintained or increased through Week 52.²

Lebrikizumab also provided long-term clinically meaningful responses in patients, offering a multi-dimensional benefit that help achieve disease control. In a post-hoc analysis of the ADvocate 1 and 2 studies, 84 percent of patients who had responded to lebrikizumab at Week 16 achieved a clinically meaningful response in at least one domain of the disease (mild signs, symptoms or quality of life impact) after 52 weeks, and more than 57 percent achieved response across the three domains.³ This represents a status of minimal residual disease.

Improvements in absolute skin response over 16 weeks for patients with moderate-to-severe AD treated with lebrikizumab or placebo were also shared. A post-hoc analysis of the ADvocate1 and ADvocate2 trials showed that, overall, a significantly higher proportion of patients treated with lebrikizumab achieved EASI ≤7 (mild) and EASI ≤1 (clear/almost clear) at Week 16 compared to placebo. This analysis also demonstrated that, regardless of baseline severity, over 50 percent of patients treated with lebrikizumab 250 mg every other week on monotherapy for 16 weeks achieved an EASI score indicating mild AD and approximately 20 percent achieved an EASI score indicating clear or almost clear skin.⁴

“Atopic dermatitis (AD) is a debilitating chronic skin condition that can be challenging to manage. Cyclosporine A is the only classical systemic treatment approved in Europe for AD, but its safety may limit long-term use, or it may be contraindicated for some patients,” said Prof. Dr. Ricard B. Warren, Professor of Dermatology and Honorary Consultant Dermatologist at the University of Manchester and Northern Care Aliance NHS Foundation Trust; principal investigator of the ADvantage trial. “Although there are an increasing number of treatment options available to ease symptoms and improve outcomes of AD, unfortunately there are few that offer long-term disease control with a favorable safety profile. The results of this trial reinforce our confidence that lebrikizumab is a promising potential new treatment for patients with moderate-to-severe AD, including those not adequately controlled or ineligible for treatment with cyclosporine A.”

“The new lebrikizumab data set presented at the EADV congress provides further evidence of its efficacy and safety profile. Its anticipated addition to the moderate-to-severe AD treatment arsenal is promising news for both healthcare professionals and patients, including those who do not respond adequately to cyclosporine. Our teams are diligently working to increase our level of knowledge and expand the body of evidence, thereby reinforcing the profile of this potential first-line treatment,” stated Karl Ziegelbauer, Ph.D., Chief Scientific Officer at Almirall.

Almirall received a positive CHMP opinion in September, recommending marketing authorization for 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 AD who are candidates for systemic therapy. The CHMP opinion is based on three pivotal Phase 3 studies^† including ADvocate 1 and ADvocate 2, evaluating lebrikizumab as monotherapy, and ADhere, assessing lebrikizumab in combination with TCS, in adult and adolescent patients with moderate-to-severe AD.

Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe. Eli Lilly and Company has exclusive rights for the development and commercialization of the product in the United States and the rest of the world, not including Europe. Almirall expects regulatory decisions for lebrikizumab in moderate-to-severe AD in additional European markets, including the United Kingdom and Switzerland in 2024.

^† More information about the Phase 3 studies: ADvocate 1: EudraCT Number 2019-002932-10; NCT04146363; ADvocate 2: EudraCT Number 2019-002933-12; NCT04178967; ADhere: EudraCT Number 2019-004300-34; NCT04250337

About lebrikizumab and Clinical Development Program

Lebrikizumab is an investigational, monoclonal antibody that binds IL-13 with high affinity to specifically prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13.^5,6,7 The cytokine IL-13 is key in AD, driving the type-2 inflammatory loop in the skin, leading to skin barrier dysfunction, itch, skin thickening and infection.^8,9,10,11,12

The lebrikizumab Phase 3 program consists of five key global studies evaluating over 1,300 patients, including two monotherapy studies (ADvocate 1 and 2), a combination study with topical corticosteroids (ADhere), as well as long-term extension (ADjoin) and adolescent open label (ADore) studies.

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 €878.5MM.

For more information, please visit www.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.

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¹ 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.

² 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 32 European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3117.

³ Vestergaard C, et al. Lebrikizumab provides long-term clinically meaningful responses in patients with moderate-to-severe atopic dermatitis Presented at the 32 European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 3399.

⁴ Fernández-Peñas P, et al. Absolute EASI improvements over 16 weeks in patients with moderate-to-severe atopic dermatitis treated with lebrikizumab or placebo Presented at the 32 European Academy of Dermatology and Venereology (EADV) Congress, 11 – 14 October 2023, Berlin, Germany. Abstract 6004.

⁵ Okragly A, et al. Binding, Neutralization and Internalization of the Interleukin-13 Antibody, Lebrikizumab. Dermatol Ther (Heidelb). 2023;13(7):1535-1547. doi:10.1007/s13555-023-00947-7.

⁶ Ultsch M, et al. Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J Mol Biol. 2013;425(8):1330-1339. doi:10.1016/j.jmb.2013.01.024.

⁷ Simpson EL, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863-871.e11. doi:10.1016/j.jaad.2018.01.017.

⁸ Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75(1):54–62. doi:10.1111/all.13954.

⁹ Tsoi LC, et al. Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. J Invest Dermatol. 2019;139(7):1480-1489. doi:10.1016/j.jid.2018.12.018.

¹⁰ Napolitano M, et al. The hidden sentinel of the skin: An overview on the role of interleukin-13 in atopic dermatitis. Frontiers in medicine vol. 10 1165098. 18 Apr. 2023, doi:10.3389/fmed.2023.1165098.

¹¹ Bernardo D, et al. Lebrikizumab for the Treatment of Moderate-to-Severe Atopic Dermatitis. Am J Clin Dermatol 24, 753–764 (2023). https://doi.org/10.1007/s40257-023-00793-5.

¹² Gonçalves F, et al. Selective IL-13 inhibitors for the treatment of atopic dermatitis. Drugs in context vol. 10 2021-1-7. 30 Mar. 2021, doi:10.7573/dic.2021-1-7.

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