S100A12

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

PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc., (NASDAQ: ARWR) today announced that it is scheduled to participate in the following upcoming events: Citi’s 18th Annual BioPharma Conference – September 6, 2023 Type: 1-on-1 Investor Meetings European Respiratory Society (ERS) International Congress – September 9-13, 2023 Date: Sept. 10, 2023, 12:30-14:00 CEST Type: Poster Session 146 Title: A Clinical-Stage Inhaled RNAi Therapeutic for Pulmonary Inflammation Mediates Durable RAGE Silencing in Nonhuman Primates Date: Sept. 10, 2023, 12:30-14:00 CEST Type: Poster Session 146 Title: A Lung-Targeted RNAi Therapeutics Delivery Platform Compatible with Subcutaneous Administration Mediates Pulmonary RAGE Silencing in Rodents and Nonhuman Primates Date: Sept. 10, 2023, 12:30-14:00 CEST Type: Poster Session 146 Title: Silencing TSLP Expression with a Lung-targeted RNAi Molecule Suppresses Pulmonary Allergic Inflammation Date: Sept. 11, 2023, 11:00-12:15 CEST Type: Late Breaking Abstract Title: A First-in-human Study of ARO-RAGE, an RNAi Therapy Designed to Silence Pulmonary RAGE Expression Date: Sept. 12, 2023, 8:00-9:30 CEST Type: Poster Session 383 Title: A Clinical-stage RNAi Therapeutic Candidate for IPF Mediates Durable MMP7 Silencing in Nonhuman Primates and Human Lung Tissue Baird 2023 Global Healthcare Conference – September 12, 2023 Type: Fireside Chat Presentation Morgan Stanley 21st Annual Global Healthcare Conference – September 13, 2023 Type: Fireside Chat Presentation 2023 Cantor Fitzgerald Global Healthcare Conference – September 27, 2023 Type: Fireside Chat Presentation Webcast links and presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

The identification of a cell metabolism process found in Black men with diabetes and prostate cancer could one day lead to the development of a disease prediction tool for this high-risk population LOS ANGELES, Aug. 15, 2023 /PRNewswire/ -- Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States and a leading research center for diabetes and other life-threatening illnesses, have identified a cell metabolism process found in men with diabetes and metastatic prostate cancer that could one day lead to improved testing and treatments for Black men with these diseases. The research will be highlighted in the press program for the American Chemical Society (ACS) Fall 2023, a hybrid meeting that will be held virtually and in person in San Francisco from Aug. 13 to 17. Continue Reading Scientists at City of Hope have identified a cell metabolism process found in men with diabetes and metastatic prostate cancer that could one day lead to improved testing and treatments for Black men with these diseases. (Photo credit: City of Hope) Black men are more than twice as likely than other men to die from prostate cancer. In a continued search to develop inclusive diagnostic and predictive tests and personalized treatments, City of Hope researchers conducted a small clinical trial that identified four metabolism-related biomarkers linked to an increased risk of metastatic prostate cancer, or prostate cancer that has spread to other parts of the body, in men of West African heritage. City of Hope leads the nation in having the first research department focused on the intersection between cancer and diabetes. "We have identified genetic and molecular changes that can be developed into a tool to predict which Black men are at the highest risk of developing metastatic prostate cancer," said Sarah Shuck, Ph.D., principal investigator of the trial who will present the data at ACS. Shuck is an assistant professor in the Arthur Riggs Diabetes & Metabolism Institute and Department of Diabetes & Cancer Metabolism at City of Hope. "This test would give doctors the ability to more accurately predict patients' prognoses and equip scientists with more data as they work to design therapies that prevent prostate cancer from developing in the first place," Shuck added. The problem appears to be production of a highly reactive compound known as methylglyoxal (MG), a byproduct of metabolism that is elevated in people with diabetes. MG binds to DNA, RNA and protein, creating a complex that may promote cancer emergence due to its instability and disrupted function. Prostate cancer is the second most common cancer in men. Black men are 70% more likely than white men to be diagnosed with prostate cancer and two to four times more likely than other racial and ethnic groups to die from the disease, according to 2023 data from the American Cancer Society. Diabetes is a chronic metabolic disease characterized by elevated levels of blood glucose or sugar, which over time leads to serious damage to the heart, blood vessels, eyes, kidneys and nerves. Black adults are 60% more likely than white adults to be diagnosed with diabetes and twice as likely to die from diabetes, according to the most recent data available from the U.S. Department of Health and Human Services Office of Minority Health. Shuck's lab focuses on the study of how metabolic dysregulation causes diabetes and cancer. She and her colleagues investigate the biochemistry involved when excess sugar damages important molecules. To see if the identified dysregulated complexes were linked to race and genetics, the team conducted a small clinical study where they gathered blood samples from 371 men with and without prostate cancer from across the nation. To determine race, they assessed samples for genetic evidence of West African heritage using methods developed by collaborators Rick Kittles, Ph.D., M.S., and Leanne Woods-Burnham, Ph.D., who were at City of Hope when the research was conducted. Next the researchers, including John Termini, Ph.D, professor in the Department of Cance Biology and Molecular Medicine at City of Hope, looked at four biomarkers associated with MG and the complexes it forms with DNA, RNA and protein. The biomarkers also included variation in a gene, GLO1, that encodes a protein which detoxifies these complexes. Surprisingly, the men of West African descent had fewer of these malignancy-promoting complexes in their blood. Contrary to expectations, a lower level of these complexes was linked to greater risk of metastatic disease. The researchers hypothesize that, in men of West African descent, tumor cells sequester these complexes and spur metastatic processes from within. These findings did not apply to men of European descent. (In technical terms, they hypothesize that MG-AGEs, sRAGE, GLO1 and AGER SNPs may be used as biomarkers for prostate cancer in Black men and that the gene variation GLO1 may play a role in the accumulation of mutations that lead to prostate cancer cell growth.) City of Hope researchers intend to gain a better understanding of prostate cancer disparities in the hopes of developing a diagnostic test. A recorded media briefing on this topic will be posted Tuesday, Aug. 15, by 7 a.m. Pacific Time at acs.org/acsfall2023briefings. The work was supported by City of Hope's Health Equities Pilot Grant. ABSTRACT Reactive metabolic by-products induced by the exposome are associated with and may drive prostate cancer metastasis in African American men Prostate cancer (PCa) is the second highest cause of cancer-related deaths in men. African American/Black (AA/B) men are disproportionally impacted by PCa with a 60% higher incidence of disease and a 2-fold increase in mortality risk compared to European American (EA) men. There is an urgent need to elucidate the underlying biological changes that give rise to this disparity to develop inclusive diagnostic and predictive tests and tailored therapeutic treatments. Environmental factors (the exposome) are proposed to contribute to this disparity and can influence disease risk through gene-environment interactions, in which genotypes may influence the response to environmental exposure. A significant contributor to PCa mortality is diabetes incidence, which varies due to the exposome. The mechanisms involved in increased PCa mortality in men with diabetes are not clear but are proposed to arise from physiological changes caused by diabetes-associated metabolic alterations. A proposed mechanism for how these changes increase PCa mortality is through the production of the reactive electrophile methylglyoxal (MG). MG is a by-product of lipid, protein, and sugar metabolism and forms covalent adducts on DNA, RNA, and protein. These adducts, termed MG-advanced glycation end products (MG-AGEs) lead to DNA mutations and genomic instability, change RNA stability and translation, and alter protein stability and function. In addition, MG-AGEs bind and activate the receptor for AGEs (RAGE). To regulate MG and MG-AGEs, cells use glyoxalase 1 (GLO1) to detoxify MG and soluble RAGE (sRAGE) to sequester MG-AGEs and prevent RAGE activation. These components comprise the AGE/RAGE axis. To define the association of MG-AGEs, GLO1, RAGE, and sRAGE with PCa health disparities, we designed a clinical study of AA/B and EA men with and without PCa. We measured serum MG-AGEs using mass spectrometry, serum sRAGE using ELISA, and sequenced the GLO1 and AGER (gene encoding RAGE) loci in genomic DNA isolated from whole blood. We discovered that MG-AGEs, sRAGE, and GLO1 and AGER SNPs were significantly associated with PCa in AA/B men but not EA men. We also observed a significant difference between these components in AA/B and EA men without PCa. This led us to hypothesize that MG-AGEs, sRAGE, and GLO1 and AGER SNPs may have utility as biomarkers for PCa in AA/B men and that GLO1 SNPs may play a role in the accumulation of MG-AGEs, mutations, and PCa cell growth. About City of Hope City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn. SOURCE City Of Hope