HIF-1α

SAN FRANCISCO--( BUSINESS WIRE )-- BIOMAKERS , a Precision Medicine & Biotech Company that supports data-driven Drug Development globally, and TOPAZIUM , an AI-driven healthtech company specializing in drug discovery and human wellbeing, have announced the results of their innovative collaborative project. This partnership showcases the power of AI systems in leveraging real-world DNA sequencing data to identify novel targets aimed at improving the efficacy of immunotherapy for non-small cell lung cancer (NSCLC) treatment. The findings were presented at the prestigious 2024 American Society of Clinical Oncology (ASCO) meeting in Chicago. The study used Whole Exome Sequencing (WES) data from biopsies of squamous and adenocarcinoma NSCLC processed through BIOMAKERS ' advanced DNA sequencing platforms. The data was then analyzed using GFPrint™, a proprietary algorithm developed by TOPAZIUM , that generates virtual representations of tumor exomes in a latent space defined by the genetic features of the samples. “The advent of drugs targeting the PD-1/PD-L1 axis has revolutionized NSCLC treatment. Although promising, individual responses to these therapies can vary, and we believe this ongoing project will help to better understand mechanisms involved in PD1/PD-L1 expression, optimize treatment protocols, and identify which patients are most likely to benefit from these therapies. In this study, DNA sequencing and GFPrint™ were employed to identify mutations in genes linked to PD-L1 expression in NSCLC adenocarcinoma tumor samples,” said Dr. Rubén Salanova, Chief Medical Officer & Co-Founder of BIOMAKERS . “Using this strategy, we have identified a subpopulation of adenocarcinoma patients with increased PD-L1 expression levels, enriched in non-silent mutations of 10 genes of interest, mostly included in the HIF-1α signaling pathway. Notably, 6 of these mutated genes (PIK3R1, HK1, NOS2, NRAS, BRAF, ITGA1) were uniquely found in adenocarcinomas” said Juan Manuel Domínguez, Head of Preclinical & Biostatistics at TOPAZIUM . “All these newly identified genes deserve further studies to validate them as potential targets for pharmacological intervention concomitant with PD-1/PD-L1 blockade, and as potential biomarkers for patient selection to improve the efficiency of immunotherapy in NSCLC treatment,” added Andrea Mendoza, Head of R&D at BIOMAKERS . For more details, the abstract can be accessed at: https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13600 For more information about GFPrint™, visit: https://www.biorxiv.org/content/10.1101/2024.03.08.584090v4 About BIOMAKERS: BIOMAKERS is an Oncology Precision Medicine Company with a Comprehensive Genomic Platform and reach throughout LATAM, delivering care-changing solutions. In addition to its strong focus on physician support and patient care, their Life Science division partners with biopharma companies to advance R&D programs by providing support for Drug Discovery and Drug Development. This innovative work is enabled by direct partnerships with renowned Health Institutions across 17 different countries. contacto@biomakers.net About TOPAZIUM: TOPAZIUM is committed to supporting medical research with artificial intelligence (AI) through state-of-the-art analytical tools. They have developed a comprehensive AI engine that utilizes multiple medical data types to assist in identifying new disease patterns and the most promising therapeutic approaches, striving to achieve one of the most challenging global goals: health for all. info@topazium.com

FARMINGTON HILLS, Mich., June 06, 2024 (GLOBE NEWSWIRE) -- Ocuphire Pharma, Inc. (Nasdaq: OCUP) (“Ocuphire”), a clinical-stage biopharmaceutical company focused on developing small molecule therapies for the treatment of patients with retinal and refractive eye disorders, today announced that clinical updates on the Company’s lead candidate APX3330 for diabetic retinopathy (DR) will be featured in upcoming presentations at the Clinical Trials at the Summit meeting on June 8 in Park City, Utah, and the Retinal Imaging Biomarkers & Endpoints Summit meeting June 25-27 in Boston. APX3330 is an oral small-molecule inhibitor of Ref-1 (reduction oxidation effector factor-1 protein) being developed for the treatment of non-proliferative diabetic retinopathy (NPDR). DR affects approximately 10 million of the 38 million Americans with diabetes and is the leading cause of blindness in working age adults, and 80 percent of DR patients have NPDR. “Clinical Update on Oral APX3330 for Diabetic Retinopathy” will be presented by Veeral Sheth, M.D., M.B.A., a practicing retina specialist at University Retina and Clinical Assistant Professor at the University of Illinois, at the Clinical Trials at the Summit meeting. Clinical Trials at the Summit brings together a diverse group of experts to discuss ongoing clinical trials and the latest data to accelerate advances in vitreoretinal care. “Multiplex Analysis of Clinical Imaging & Biomarker Data to Validate Novel Endpoints for Diabetic Retinopathy” will be presented by Ashwath Jayagopal, Ph.D., Ocuphire’s Chief Scientific and Development Officer, at the second annual Retinal Imaging Biomarkers & Endpoints Summit. The Retinal Imaging Biomarkers & Endpoints Summit is the only industry-dedicated event focusing on streamlining imaging data analysis with the implementation of AI-based predictive measures for earlier detection and diagnosis to optimize patient stratification, selection and recruitment for trials. “APX3330 has the potential to be a novel treatment that addresses multiple established disease pathways for NPDR,” said George Magrath, M.D., M.B.A., M.S., Ocuphire’s Chief Executive Officer. “We are grateful for multiple opportunities to share an update on our APX3330 clinical program and our planned ZETA-2 pivotal trial, including the unmet need for an earlier intervention treatment to delay or prevent DR progression, the value of multimodal imaging in DR, and Phase 2/3 trial optimization and patient selection, with industry and scientific peers.” Ocuphire anticipates initiating the ZETA-2 Phase 2/3 trial of APX3330 for NPDR in early 2025. About Ocuphire Pharma Ocuphire is a clinical-stage ophthalmic biopharmaceutical company focused on developing novel therapies for the treatment of retinal and refractive eye disorders. Ocuphire’s lead retinal product candidate, APX3330, is an oral small-molecule inhibitor of Ref-1 (reduction oxidation effector factor-1 protein) for the treatment of non-proliferative diabetic retinopathy (NPDR). Ref-1 is a regulator of the transcription factors HIF-1α and NF-κB. Inhibiting REF-1 reduces levels of vascular endothelial growth factor (VEGF) and inflammatory cytokines which are known to play key roles in ocular angiogenesis and inflammation. APX3330 is an oral tablet to be administered twice per day for the treatment of diabetic retinopathy (DR). A Phase 2 study in subjects with DR and an End-of-Phase 2 meeting have been completed, and a special protocol assessment (SPA) was submitted to the U.S. Food and Drug Administration (FDA) in February 2024. In addition, Ocuphire has a partnership to develop and commercialize Phentolamine Ophthalmic Solution 0.75% (“PS”), a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. PS was approved by the FDA for the treatment for pharmacologically-induced mydriasis under the brand name RYZUMVI™ in September 2023. PS is also in Phase 3 clinical development for the treatment of presbyopia and for the treatment of decreased visual acuity under low light (mesopic) conditions after keratorefractive surgery. Ocuphire is also developing APX2009 and APX2014, second-generation analogs of APX3330. These programs are being evaluated for treating other retinal diseases such as age-related macular degeneration and geographic atrophy. For more information, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the efficacy of APX3330 in slowing the progression of diabetic retinopathy, the safety and tolerability of APX3330, ongoing discussions with the FDA regarding various of our drug products, and continued drug development under our partnership agreement. These forward-looking statements relate to us, our business prospects and our results of operations and are subject to certain risks and uncertainties posed by many factors and events that could cause our actual business, prospects and results of operations to differ materially from those anticipated by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those described under the heading “Risk Factors” included in our Annual Report on Form 10-K. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “aim”, “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. We undertake no obligation to revise any forward-looking statements in order to reflect events or circumstances that might subsequently arise. These forward-looking statements are based upon Ocuphire’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: The success and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; Regulatory requirements or developments; Changes to or unanticipated events in connection with clinical trial designs and regulatory pathways; Delays or difficulties in the enrollment of patients in clinical trials; Substantial competition and rapid technological change; Our development of sales and marketing infrastructure; Future revenue losses and profitability; Our relatively short operating history; Changes in capital resource requirements; Risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; Domestic and worldwide legislative, regulatory, political and economic developments; Employee misconduct; Changes in market opportunities and acceptance; Reliance on third-parties; Future, potential product liability and securities litigation; System failures, unplanned events, or cyber incidents; The substantial number of shares subject to potential issuance associated with our equity line of credit arrangement; Risks that our partnership or other licensing arrangements, may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; Future fluctuations in the market price of our common stock; The success and timing of commercialization of any of Ocuphire’s product candidates; and Obtaining and maintaining Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive. Readers are urged to carefully review and consider the various disclosures made by us in this report and in our other reports filed with the Securities and Exchange Commission that advise interested parties of the risks and factors that may affect our business. All forward-looking statements contained in this press release speak only as of the date on which they were made. Ocuphire undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Contacts Corporate Investor Relations Nirav Jhaveri, M.B.A. CFO ir@ocuphire.com Corey Davis, Ph.D. LifeSci Advisors cdavis@lifesciadvisors.com

NEW YORK, May 20, 2024 /PRNewswire/ -- A certain biological pathway, a set of linked reactions in the body, drives the inflammation seen in the skin disease psoriasis, a new study finds. The work could lead to improved therapies for all inflammatory skin diseases, including atopic and allergic dermatitis and a type of boil called hidradenitis suppurativa, say the study authors. Inflammation is the body's natural response to irritation and infection, but when out of control, it can lead to the reddish, flaky, itchy lesions that come with these skin diseases. Led by researchers at NYU Langone Health, the new study found that the interleukin-17 (IL-17) pathway, whose activity is blocked by existing anti-inflammatory drugs, activates a protein called hypoxia inducible factor 1-alpha (HIF-1-alpha) in psoriasis. Researchers say that IL-17 has long been known to be active in inflammation, but the role of HIF-1-alpha has until now been unclear. The research team also found that HIF-1-alpha let inflamed skin cells more actively break down sugar for energy, supporting their metabolism and leading to the production of a waste product called lactate. When consumed by inflammatory T cells, lactate triggered production of IL-17, fueling even more inflammation. Publishing in the journal Immunity online May 20, the findings show that in human skin tissue samples from people with psoriasis, measures of gene activity around IL-17 and HIF-1-alpha were similar, suggesting that these factors are interconnected. Experiments in mice treated to develop psoriasis found that subsequent treatment with an experimental drug that blocks the action of HIF-1-alpha, called BAY-87-2243, resolved inflammatory skin lesions. Further, skin samples from 10 patients successfully treated with anti-inflammatory drug etanercept showed diminished activity for both IL-17 and HIF-1-alpha, suggesting to researchers that when IL-17 is blocked, so is HIF-1-alpha. "Our study results broadly show that activation of HIF-1-alpha is at the crux of metabolic dysfunction observed in psoriasis and that its action is triggered by IL-17, another key inflammatory-signaling molecule," said corresponding study author Shruti Naik, PhD, associate professor at NYU Grossman School of Medicine in the Departments of Pathology and Medicine, and the Ronald O. Perelman Department of Dermatology. Further experiments were performed on skin samples from five patients with psoriasis whose healthy and inflamed skin was separately treated with either BAY-87-2243 or an existing combination of topical drugs (calcipotriene and betamethasone dipropionate). Researchers then compared differences in inflammatory gene activity as a measure of impact and found that the HIF-1-alpha inhibitor had a greater effect than existing topical drugs. Specifically, skin samples that responded to HIF-1-alpha therapy had 2,698 genes that were expressed differently, while standard-of-care–treated samples had 147 differently expressed genes. Genetic analysis of skin samples from another 24 psoriatic patients treated with the IL-17A–blocking drug secukinumab showed only decreased, not heightened, gene activity connected to HIF-1-alpha when compared to HIF-1-alpha gene activity in nine healthy patients with no psoriatic disease. Researchers say this indicates HIF-1-alpha's blocked action was codependent on blockage of IL-17. Additional experiments in mice showed that blocking sugar (glucose) uptake in the skin slowed psoriatic disease growth by limiting glucose metabolism, or glycolysis. Both the number of immune T cells tied to inflammation and the cell levels of IL-17 also decreased. The researchers found further that levels of lactate, the main byproduct of glycolysis, in psoriatic skin cell cultures dropped once exposed to the glycolysis-inhibiting drug 2-DG. Directly targeting lactate production in psoriatic mice using a topical skin cream containing lactate dehydrogenase, which breaks down lactate, also slowed disease progression in the skin, with reduced numbers of inflammatory gamma-delta T cells and reduced IL-17 activity. Gamma-delta T cells were shown to take up lactate and use it to produce IL-17. "Our findings suggest that blocking either HIF-1-alpha's action or its glycolytic metabolic support mechanisms could be effective therapies for curbing the inflammation," added Naik, who is also the associate director for NYU Langone's Judith and Stewart Colton Center for Autoimmunity. "Evidence of HIF-1-alpha's depressed action, or downregulation, could also serve as a biomarker, or molecular sign, that other anti-inflammatory therapies are working," said study co-senior investigator Jose U. Scher, MD, the Steere Abramson Associate Professor of Medicine in the Department of Medicine at NYU Grossman School of Medicine. Scher, who also serves as director of NYU Langone's Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity, says the team plans to develop experimental drugs that can block HIF-1-alpha and lactate action in the skin "to end the underlying vicious cycle of IL-17–driven inflammation in skin disease. Our research fundamentally expands the scope of feasible therapeutic options." Naik points out that while many available therapies for psoriasis, including steroids and immunosuppressive drugs, reduce inflammation and symptoms, they do not cure the disease. She said further experiments are needed to refine which experimental drug works best, with respect to HIA-1-alpha inhibition, before clinical trials could start. Indeed, Naik and study co-lead investigators Ipsita Subudhi and Piotr Konieczny have a patent application pending (U.S. application number 63/540,794) for inflammatory skin disease therapies derived from their work on HIA-1-alpha inhibition. More than 8 million Americans and 125 million worldwide are estimated to have psoriatic disease. The condition affects men and women equally. Funding support for the studies was provided by National Institutes of Health grants P30AR075043, R01AR080436, R01AI168462, UC2AR081029, K22AI135099, K99AR083536, T32AR069515, TL1TR001447, UL1TR001445, and DP2AR079173. Additional funding was provided by the National Psoriasis Foundation, the Judith and Stewart Colton Center for Autoimmunity, the Beatrice Snyder Foundation, the Riley Family Foundation, the American Association of Immunologists, the International Human Frontier Science Program, the Charles H. Revson Foundation, and the Pew-Stewart Scholar Award 00034119, as well as the New York Stem Cell Foundation. Naik serves on the advisory boards of Seed Inc. and as a consultant for BiomX. She also receives research funding from Takeda Pharmaceuticals. Scher has served as a consultant for Janssen, Pfizer, UCB, and BMS. He also receives research funding from Janssen and Pfizer. All of these arrangements are being managed in accordance with the policies and practices of NYU Langone Health. Besides Naik, Scher, Subudhi, and Konieczny, other NYU Langone investigators were Aleksandr Prystupa, Rochelle Castillo, Erica Sze-Tu, Yue Xing, Daniel Rosenblum, Ilana Reznikov, Ikjot Sidhu, Cynthia Loomis, Catherine Lu, and Aristotelis Tsirigos. Other study co-investigators were Niroshana Anandasabapathy, at Weill Cornell Medicine; Mayte Suarez-Farinas, at the Icahn School of Medicine at Mount Sinai; and Johann Gudjonsson, at the University of Michigan. Contact: Gregory Williams, [email protected] SOURCE NYU Langone Health