CAMP

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

ROCKVILLE, Md. and SUZHOU, China, Dec. 4, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and UNION therapeutics A/S (UNION), a privately-held, multi-asset, clinical stage, pharmaceutical development company focused on immunology and infectious diseases, today announced that the first Chinese healthy volunteer has been successfully dosed in the Phase I study of orismilast (Innovent R & D code: IBI353), a potential best-in-class PDE4 inhibitor in global clinical Phase II stage. This study (CTR 20222393) is a multiple dose escalation Phase I study in healthy volunteers aiming to evaluate the pharmacokinetic (PK) profile, safety and tolerability of orismilast in healthy Chinese subjects after multiple doses to support the subsequent clinical development of orismilast in multiple indications such as psoriasis and atopic dermatitis (AD). Orismilast is a next-generation PDE4 inhibitor with high potency for the PDE4 subtypes linked to inflammation. In 2021, Innovent reached a strategic cooperation with UNION to obtain exclusive rights to the research, development and commercialization of orismilast in China (including mainland China, Hong Kong, Macao and Taiwan). Orismilast has generated positive proof of concept (PoC) data in psoriasis (administered orally) and in AD (administered topically) and is being developed as a potential best- or first-in-class oral treatment option in both diseases. Compared to other PDE4 inhibitors, the selectivity of orismilast for PDE4 subtypes B and D and the novel modified release delivery is expected to generate a favorable therapeutic window, potentially resulting in improved efficacy and tolerability. Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: 'There is currently no cure for psoriasis, and there is a great unmet clinical need in this field. Orismilast is a new target molecule Innovent laid out in the field of autoimmunity by co-development with UNION. It is potentially one of the best candidates in the mid-stage of clinical development at Innovent. The results of ex-China clinical studies have demonstrated that orismilast has good safety profile and biological activity. The ongoing Phase I study will evaluate the safety and tolerability of orismilast in Chinese healthy volunteers and provide the basis for further clinical development. We will accelerate the clinical development of orismilast in Chinese subjects with psoriasis or AD in order to obtain regulatory approval as soon as possible in China and to fulfill the needs of safe, effective and convenient long-term oral treatment for patients, thus significantly reducing the disease burden of patients and their pain. We will truly uphold our mission of "To develop and commercialize high-quality biopharmaceuticals that are affordable to ordinary people".' Kim Kjøller, CEO of UNION therapeutics, stated: 'We are excited by the strong advancement of orismilast by Innovent, which is essential in our joint efforts to provide this novel treatment to patients with dermatological diseases globally. We have seen good progress in our three late-stage clinical trials with orismilast for treatment of psoriasis, atopic dermatitis, and hidradenitis suppurative, respectively. This, together with the now ongoing Phase I study in China, is important steps in the development of orismilast.' About Psoriasis and atopic dermatitis (AD) Psoriasis is a multisystem disease characterized by well-defined erythematous scaly plaques that are often pruritic. Estimates of psoriasis prevalence range from 0.51% to 11.43% in adults and 0% to 1.37% in children[1].Psoriasis is a common disease that occurs more frequently with age. The most common clinical type of psoriasis is psoriasis vulgaris (plaque psoriasis). The involvement of inflammatory cells (e.g., T cells and myeloid dendritic cells) and pro-inflammatory cytokines (e.g., tumor necrosis factor-α, interleukin (IL) -12, and IL-17) in the pathogenesis of psoriasis has been well documented [2]. There is currently no cure for psoriasis. Psoriasis vulgaris can be managed with local therapy, phototherapy, or systemic therapy or any combination of these. It is estimated that around 80% of psoriasis patients have mild to moderate psoriasis[3] [4] , for those patients topical therapy is used first line. About one-third of psoriasis patients experience moderate-to-severe disease, systemic medications (biologic or nonbiologic) or phototherapy are preferred regimens for such patients[5]. However, long term treatment of psoriasis with topical therapies (e.g. TCS), biologic therapies (eg, antibodies) is often limited by safety and tolerability issues, with decreasing efficacy over time, thus resulting in poor patient adherence due to inconvenient routes of administration (eg, injections) [6]. Therefore, there is an unmet need for safe, effective, and convenient long-term oral therapy for patients with psoriasis. Atopic Dermatitis (AD) is a chronic inflammatory disease characterized by eczematous lesions and intense pruritus, affecting up to 20% of children and up to 3% of adults[7].Inflammatory infiltrates in these skin lesions include T lymphocytes, neutrophils, eosinophils, monocytes, macrophages, and mast cells[8].High levels of PDE4 activity have also been identified in leukocytes of these patients[9].AD is usually treated with topical therapies, primarily intermittent prophylactic use of topical corticosteroids and/or topical calcineurin inhibitors, along with daily emollients. Intermittent corticosteroid use poses minimal risk of corticosteroid-related adverse effects such as skin atrophy, striae formation in sensitive or thin skin areas, and systemic effects. However, long-term adherence to topical therapy was low. Off-label use of other conventional systemic oral immunomodulators such as cyclosporine, azathioprine, and methotrexate may be effective in adult AD patients, but patients discontinue treatment due to adverse events or lack of efficacy. Use of these agents has known safety limitations and requires regular laboratory monitoring. Therefore, better systemic treatment options are needed, particularly for AD patients who do not respond well to topical treatment. Dupilumab, a subcutaneous biologic therapy targeting IL-4 and IL-13 receptors, is approved by the US Food and Drug Administration for the treatment of moderate to severe AD in adults. The need for oral treatment options remains imperative in this disease state. About Orismilast IBI353 (Orismilast) is a next-generation PDE4 inhibitor with high potency for the PDE4 subtypes linked to inflammation currently under development as an oral treatment for psoriasis, AD and HS. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE that is expressed by immune and inflammatory cells, including T lymphocytes, neutrophils, eosinophils, monocytes, dendritic cells, and macrophages[10]. In these cells PDE4 is the predominant PDE form and PDE4 inhibitors increase cAMP levels. High cAMP levels tend to reduce proliferation and cytokine production, whereas low concentrations of cAMP have the opposite effects. PDE4 inhibition has previously been shown to downregulate production of a range of proinflammatory cytokines[11]-[13]. Consistent with previously published work, orismilast demonstrates a potent and broad anti-inflammatory effect by inhibiting the secretion of Th1 (TNFα and IFNg, Th17 (IL-22 and IL-23), and Th2 (IL-4, IL-5 and IL-13) effector cytokines in human PBMCs. In addition, potent inhibition of innate cytokines (IL-1α and IL-1b ) was also observed. These results support further development of orismilast as a potential best-in-class or first-in-class PDE4 inhibitor for the treatment of chronic inflammatory skin diseases including psoriasis, HS and AD. About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines in the fields of oncology, metabolic, autoimmune, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK. Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT (sintilimab injection), BYVASDA (bevacizumab biosimilar injection), SULINNO (adalimumab biosimilar injection), HALPRYZA (rituximab biosimilar injection), Pemazyre (pemigatinib oral inhibitor), olverembatinib （BCRABLTKI, Cyramza (ramucirumab) and selpercatinib. An additional 2 assets are under NMPA NDA review, 5 assets are in Phase 3 or pivotal clinical trials, and 20 more molecules are in clinical studies. Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: . and . Note: TYVYT® (sintilimab injection) is not an approved product in the United States. BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States. TYVYT® (sintilimab injection, Innovent) BYVASDA® (bevacizumab biosimilar injection, Innovent) HALPRYZA® (rituximab biosimilar injection, Innovent) SULINNO® (adalimumab biosimilar injection, Innovent) Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan. CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Selpercatinib (Eli Lilly). Selpercatinib was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Disclaimer: 1. This indication is still under clinical study, which hasn't been approved in China. 2. Innovent does not recommend any off-label usage. About UNION therapeutics UNION therapeutics is a privately-held, multi-asset, clinical stage, pharmaceutical development company focused on immunology and infectious diseases. The company is currently working with two complementary chemistry classes, spanning immunology and microbiology with multiple candidates in clinical development. UNION is headquartered in Hellerup, Denmark, and led by an international team consisting of biotech entrepreneurs and senior pharma executives, with a collective track record of developing and launching more than fifteen marketed drugs. Read more at Innovent's Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect. Reference: [1]. Michalek IM, Loring B, John SM. A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol. 2017 Feb;31(2):205-212. doi: 10.1111/jdv.13854. Epub 2016 Aug 30. [2]. Quaglino P, Bergallo M, Ponti R, Barberio E, Cicchelli S, Buffa E, et al. Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of cytokines and gene targets induced by etanercept treatment and correlation with clinical response. Dermatology. 2011;223(1):57-67. [3]. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc 2004;9:136-9 [4]. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi C, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826-50 [5]. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 5. Guidelines of care for the management and treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62:114-135. [6]. Ravindran V, Scott DL, Choy EH. A systemic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis. Ann Rheum Dis. 2008;67:855-859. [7]. Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66 Suppl 1:8-16. [8]. Cooper KD: Atopic dermatitis: recent trends in pathogenesis and therapy. J Invest Dermatol 1994, 102:128–137. [9]. Butler JM, Chan SC, Stevens S, Hanifin JM: Increased leukocyte histamine release with elevated cyclic AMP-phosphodiesterase activity in atopic dermatitis. J Allergy Clin Immunol 1983, 71:490–497. [10]. Spina D. PDE4 inhibitors: current status. Br J Pharmacol. 2008;155(3):308-315. [11]. Brideau C, Van Staden C, Styhler A, Rodger IW, Chan C-C. The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor-α and leukotriene B4 in a novel human whole blood assay. Br J Pharmacol 1999;126(4):979-88. [12]. Manning CD, Burman M, Christensen SB, Cieslinski LB, Essayan DM, Grous M, et al. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Br J Pharmacol 1999;128(7):1393-8. [13]. Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol 2012;148(8):890-7.. SOURCE Innovent Biologics