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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

Clinical Stage Oncology Biotech Leverages Active Ingredient in Abortion Pill to Induce Immunity to Cancer ELK CITY, Idaho--(BUSINESS WIRE)-- Therapeutic Solutions International, Inc. (TSOI), announced today that its Subsidiary Company Res Nova Biologics, successfully treated four advanced cancer patients with FloraStilbene™. The patients had no adverse events from drug administration and clinical signals of tumor response were observed. All patients have been followed-up with for more than three months. FloraStilbene™ is a drug comprising of a proprietary formulation of the abortion pill’s active ingredient (RU486) and pterostilbene. The drug is manufactured by Compounding Pharmacy Cure Stat1 and is available by prescription under Right To Try. Previously, the Company has demonstrated efficacy of FloraStilbene in stimulating immune responses in animal models of various cancers, with an emphasis on triple negative breast tumor models2. The use of pterostilbene for cancer immunotherapy was patented by Therapeutic Solutions International in 20173, subsequent to which, numerous independent groups have shown the ability of this compound to block prostate4, breast5, melanoma6, glioma7, and lung cancers8. “This is a major step forward in Res Nova’s development plan for FloraStilbene™. These data, combined with existing preclinical and animal studies will serve as the basis for future clinical trials which will provide the basis for FDA sales approval,” said Dr. James Veltmeyer, Chief Medical Officer and the Physician who administered the drug. “From an ethical perspective, we are proud to have the support of several major leaders of the Pro-Life Movement including Bishop Joseph L Coffey (of the Military Archdiocese)9 and Dr. George Delgado (Inventor of the Abortion Pill Reversal) who sit on the Company’s Advisory Board10.” “The brilliant founders of Res Nova, with a miraculous stroke of genius, are turning a drug that destroys life into a 'weapon' that destroys cancer to saves lives,” said Deacon Keith Esshaki, Member of the Company’s Advisory Board. “The rapid translation of FloraStilbene™ from a laboratory discovery to a compounded drug speaks volumes to the power of the team that Ms Ramos has assembled,” said Timothy Dixon, President and CEO of Therapeutic Solutions International. “Through leveraging relationships and resources provided by TSOI, we anticipate accelerated availability of FloraStilbene™ to the multitude of drug resistant cancer patients.” “Breast cancer is a major epidemic for which novel treatments and research directions are urgently needed. We are thankful to our colleagues but most importantly to the brave patients who participated in this study, which we anticipate will be the foundation for a paradigm shifting approach to this dreadful disease,” said Famela Ramos, President and CEO of Res Nova Bio, Inc. About Therapeutic Solutions International, Inc. Therapeutic Solutions International is focused on immune modulation for the treatment of several specific diseases. The Company's corporate website is . 1 Therapeutic Solutions International Spin-Off Res Nova Bio Partners with Cure Stat Rx to Manufacture First in Class Breast Cancer Immunotherapy Product FloraStilbene™ (yahoo.com) 2 Therapeutic Solutions International Subsidiary Res Nova Bio Inc Discovers New Mechanism of Action for Breast Cancer Immunotherapy Adjuvant FloraStilbene™ | BioSpace 3 US9682047B2 - Augmentation of oncology immunotherapies by pterostilbene containing compositions - Google Patents 4 Inhibition of miR-20a by pterostilbene facilitates prostate cancer cells killed by NK cells via up-regulation of NKG2D ligands and TGF-β1down-regulation: Heliyon 5 Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human Breast Cancer Cells | Anticancer Research (iiarjournals.org) 6 Pterostilbene supresses inflammation-induced melanoma metastasis by impeding neutrophil elastase-mediated thrombospondin-1 degradation – ScienceDirect 7 Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells | Scientific Reports (nature.com) 8 Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress | Scientific Reports (nature.com) 9 Bishop Coffey - Archdiocese for the Military, USAArchdiocese for the Military, USA (milarch.org) 10 Res Nova Biologics Recruits Abortion Pill Reversal Founder to Scientific Advisory Board (yahoo.com)

Clinical activity observed in 50% of evaluable patients with relapsed/refractory acute myeloid leukemia (r/r AML) or high-risk myelodysplastic syndromes (HR-MDS) treated with RVU120 monotherapy, including a complete response. Treatment continues to show a favorable safety pro 50-70% target engagement achieved at a dose of 250 mg. The published clinical and non-clinical data strongly support RVU120’s Phase II development plans presented in October. A webinar discussing the data presented at the ASH 2023 conference will take place on Sunday, December 10, at 11:00 PM (PST) / Monday, December 11, at 8:00 AM (CET).Registration is available at: ryvu.clickmeeting.com/ryvu-ash-2023-results/register. KRAKOW, Poland, Dec. 11, 2023 (GLOBE NEWSWIRE) -- Ryvu Therapeutics [WSE:RVU], a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, presents clinical and preclinical data on RVU120, a selective CDK8/19 inhibitor, at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, which is held on December 9-12, 2023, in San Diego, California. “The results from the CLI120-001 (RIVER-51) study of RVU120 in patients with r/r-AML and HR-MDS continue to improve over time. RVU120 monotherapy shows signs of clinical activity in 50% of evaluable patients, including a complete response, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with NPM1 mutation, DNMT3a mutation, and in those with HR-MDS,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “We are pleased with the 50-70% target engagement achieved at 250 mg dose, which, based on our preclinical data, is anticipated to result in robust antileukemic efficacy in selected settings.” Dr. Nogai continued: “Given the observed hematologic improvements, particularly the early signs of erythroid responses in seven patients, we believe that RVU120 holds the potential to be a novel erythropoiesis-stimulating agent for patients with LR-MDS and myelofibrosis. Furthermore, the non-clinical study supports RVU120's development as a frontline targeted therapy in AML, as evidenced by its cytotoxic and differentiating effects on well-characterized leukemic stem cell-like populations. Based on these encouraging results, we plan to initiate Phase II studies in patients with AML, HR-MDS, LR-MDS, and myelofibrosis.” Posters highlights featured at the Meeting: Abstract Title: “Safety and Efficacy Results from CLI120-001 a Phase 1 Study in RR-AML and HRMDS: Update from Higher Dose Levels” Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST Poster Number: 2913 Updated Phase I data on RVU120 at higher dose levels in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) demonstrate clinical activity with a favorable safety profile. As of the data cut-off on November 10, 2023, 38 patients (34 with AML and four with HR-MDS) have been treated in the trial at doses up to 250 mg. Of the 28 evaluable patients, 14 showed clinically relevant benefits, including eight blast reductions to <5% in the bone marrow. Among these, there was one complete response, three marrow complete responses, and four clinically relevant BM blast reductions. Five additional patients achieved transfusion independence, and one achieved an absolute difference of >4 RBC units compared to the baseline, following Cheson 2006 criteria. One patient received a transplant after nearly four months of treatment. The first evaluable patient at 250 mg showed significant blast reduction (64%) at the end of cycle 2. Doses up to 250 mg have shown a favorable safety profile, with 50-70% target engagement achieved at a dose of 250 mg. Abstract Title: “Preclinical and Clinical Evidence for Erythroid-Stimulating Activity of RVU120 CDK8/19 Inhibitor in AML and MDS” Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST Poster Number: 2800 RVU120-induced erythroid differentiation was studied in primary malignant stem cells from MDS patients and in a stem cell model. To date, early signs of erythroid response, at the molecular level measured by increased erythroid surface markers CD71 and/or CD235a expression, were observed in seven evaluable patients in the ongoing Phase Ib. Four out of seven patients had a clinically relevant hematological response. Transcriptomic analyses of bone marrow cells in patients treated with RVU120 showed specific induction of gene expression programs leading to the maturation of erythroid cells in two out of four patients, who also exhibited clinical hematologic improvement. These clinical and preclinical data support further development of RV120 as a novel erythroid stimulating agent. Treatment with RVU120 could be a promising treatment option for patients with lower-risk MDS who are transfusion-dependent and failing previous lines of treatment. Abstract Title: “Novel Clinically Useful Inhibitor of Mediator Complex, RVU120, Relieves Differentiation Block in MDS/AML” Session Name: 636. Myelodysplastic Syndromes—Basic and Translational: Poster II Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST Poster Number: 3225 Data demonstrate RVU120’s potential for erythroid-stimulating activity in CD34+ primary samples of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Treatment with RVU120 in MDS and AML models, including patient-derived sample cultures, resulted in increased erythroid differentiation, as evidenced by increased expression of erythroid surface markers. Additionally, inhibition of CKD8/19 led to transcriptional silencing in MDS-L cells. Notably, RVU120 also inhibits phosphorylation of STAT5 and STAT1, which may represent the underlying mechanism of action. These results provide supporting rationale for further development of RVU120 for transfusion-dependent MDS/AML patients. Posters are available on Ryvu corporate website. Additionally, the two posters listed below will be made public on December 11, 2023, at 9:00 AM PST/18:00 CET. Abstract Title: “Targeting CDK8/CDK19 to Disrupt Leukemic Stem Cell-like Population in Acute Myeloid Leukemia: Exploring RVU120 As a Promising Frontline Therapy” Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III Session date and time: Monday, December 11, 2023, 2023, 6:00 PM - 8:00 PM PST Poster Number: 4175 Abstract Title: “Mediator Kinase/CDK8 Inhibition as a Strategy to Improve FLT3 Inhibitor Activity in Acute Myeloid Leukemia” Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III Session date and time: Monday, December 11, 2023, 6:00 PM-8:00 PM PST Poster Number: 4173 Investor Event Ryvu will host a webinar on Sunday, December 10, at 11:00 PM PST / Monday, December 11, at 8:00 AM CET, to discuss the data presented at the ASH Annual Meeting. To join the webcast, please register here: ryvu.clickmeeting.com/ryvu-ash-2023-results/register. About Ryvu Therapeutics Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality, and immuno-oncology targets. Ryvu’s most advanced programs are RVU120 — a selective CDK8/CDK19 kinase inhibitor with potential for the treatment of hematological malignancies and solid tumors, currently in phase Ib clinical development for the treatment of acute myeloid leukemia and myelodysplastic syndromes, and phase I/II for the treatment of r/r metastatic or advanced solid tumors — and SEL24 (MEN1703), a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech, Exelixis, Menarini, and Merck. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please see . Contacts: Investors John Fraunces LifeSci Advisors +1 917-355-2395 jfraunces@lifesciadvisors.com Corporate Natalia Baranowska Ryvu Therapeutics +48 784 069 418 natalia.baranowska@ryvu.com