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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

Data demonstrates the potential of ‘1805 to reset the immune system through its unique mechanism of action across various autoimmune diseases, including inflammatory bowel disease and rheumatoid arthritisNEW ORLEANS and CAMBRIDGE, United Kingdom, June 05, 2023 (GLOBE NEWSWIRE) -- Revolo Biotherapeutics (“Revolo” or the “Company”), a company developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic diseases, today announced new pre-clinical and ex-vivo data in an oral presentation at the 5th Treg Directed Therapies Summit, showcasing the ability of its immune-resetting drug candidate ‘1805 to alter the T regulatory cell (Treg) phenotype, gene expression and inflammation in human gut tissue with inflammatory bowel disease (IBD) as well as selectively alter transcripts in macrophages harvested from rheumatoid arthritis (RA) subjects. “This compelling data shows that ‘1805 enhances CD69+ and CD39+ Tregs in human tissue afflicted with IBD and improves anti-inflammatory gene transcription. This further illustrates ‘1805 unique mechanism of action as it resets the immune system to restore immune system balance,” said Jonathan Rigby, Chief Executive Officer of Revolo. “Additional data for ‘1805 in immune cells harvested from patients with RA showcases the selective alteration of RA cell transcripts compared to controls. Altogether, this data supports our upcoming Phase 2 trial in RA as well as future efforts in ulcerative colitis and other IBD indications. We are eager to continue exploring the broad potential of ‘1805 in various indications with the goal of providing long-term disease remission in patients living with autoimmune diseases.” Data highlights include:Inflammatory Bowel Disease Enhanced generation of double positive CD69+/CD39+ FoxP3 Tregs in the inflamed lamina propria of gut biopsies from IBD patients following treatment with ‘1805 while non-inflamed tissue biopsies did not.In mononuclear cultures, ‘1805 sustains an increase in CD69 expression on Tregs as well as that of its ligands, galectin-1, and S100A8/9. When CD69 binds to its ligands, the JAK/STAT5 pathway is activated to promote Treg differentiation and prevent pro-inflammatory Th1/Th7 cell generation.CD69+/CD39+ Tregs in intestinal tissues may play an important role in immune system balance and the prevention of inflammation. Rheumatoid Arthritis Following treatment with ‘1805, macrophages harvested from RA subjects experienced a selective reduction in pro-inflammatory gene transcripts in comparison to healthy controls which showed very little alteration in transcripts.In macrophages from RA subjects, ‘1805 upregulated ~1900 genes involved in cell contact and downregulated ~1550 genes involved largely in hypermetabolic changes. Macrophages from healthy donors showed little change in gene transcripts after treatment with ‘1805. About ‘1805‘1805 is a modified analogue of the endogenous immune-regulatory binding immunoglobulin protein (BiP), a key player in immune function that resets the immune system for long-term disease remission. Its mechanism of action creates vast optionality across multiple indications and routes of administration. Revolo BiotherapeuticsRevolo Biotherapeutics is developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic diseases, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, a protein and a peptide respectively, reset the immune system to prevent the chronic pro-inflammatory immune response that results in autoimmune or allergic disease. ‘1104 is a peptide derived from a natural immune-regulatory protein and has recently completed two Phase 2a clinical trials for patients with eosinophilic esophagitis (EoE) and allergic disease. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases. For further information, please visit www.revolobio.com. Company ContactMarylyn Rigby, SVP Investor Relations & Marketing mrigby@revolobio.com Media Contact Monica Rouco Molina, Ph.D.LifeSci Communications+1-929-469-3850mroucomolina@lifescicomms.com

Researchers who identified a novel mechanism for platelet activation in pathogenic blood clotting (thrombosis) are now turning their attention to sepsis. Researchers from the University of Birmingham, UK, who identified a novel mechanism for platelet activation in pathogenic blood clotting (thrombosis) are now turning their attention to sepsis. Identified by Associate Professor Julie Rayes and Dr Martina Colicchia from the Birmingham Platelet Group, and described in a recent paper in Blood, this previously unknown axis comprises platelet receptor glycoprotein I alpha (GPIb?), and an anti-microbial protein S100A8/A9, which is released from activated immune cells. The mechanism is not blocked by classical anti-platelet drugs currently used to treat arterial thrombosis, and is distinct from the well-described 'clotting cascade' that limits blood loss following injury. Dr Rayes explains: "When clots are formed at the site of a vascular injury, two main populations of platelet are seen. Highly activated and aggregated platelets are located at the core of the clot, while procoagulant platelets are present at the shell around the core and support the generation of fibrin which stabilizes the clot. "The S100A8/A9-GPIb? axis does not induce platelet aggregation but it does induce the formation of procoagulant platelets and accelerates fibrin activation and thrombosis. This axis might be more relevant in disease states where the activation of innate immune cells and platelets play a pivotal role in clotting." High levels of S100A8/A9 are seen in the blood in thrombo-inflammatory diseases including myocardial infarction (MI), deep vein thrombosis (DVT) and infections such as COVID-19 and sepsis, and their presence correlates with thrombotic complications, and worse outcomes for patients. The researchers believe this novel mechanism may be relevant in thrombosis observed under chronic inflammatory conditions and acute infections and believe that the interaction of S100A8/A9 with multiple receptors* makes it an interesting target to limit both clotting and inflammation during sepsis. Dr Rayes said: "Thrombosis is a major complication during infection, so drugs are needed that target pathogenic clotting while maintaining vascular integrity and normal clotting process (haemostasis). By selectively targeting S100A8/A9, we aim to target a key pathogenic inflammatory and thrombotic molecule to limit both inflammation and thrombosis during infection." Associate Professor Rayes presented at the 63rd American Society of Hematology (ASH) Annual Meeting on Monday December 12, 2022 (16.30-18.05 CST). She expects to publish the results of the sepsis study in 2023. University of Birmingham Enterprise has filed a patent application covering the targeting of the S100A8/A9-GPIb? axis in the treatment and prevention of thrombosis in chronic inflammatory and thrombotic diseases and is now seeking partners for commercial development or licensing.