SFTPC

–Preclinical data for ARV-393 presented at the European Hematology Association 2024 Annual Congress showed anti-tumor activity in models of B-cell lymphoma – – Preclinical data presented at the Biennial International LRRK2 Meeting highlighted the promise of PROTAC®-induced leucine-rich repeat kinase 2 (LRRK2) degradation as a potential treatment for neurodegenerative diseases – NEW HAVEN, Conn., June 21, 2024 (GLOBE NEWSWIRE) -- Arvinas Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today announced it presented new preclinical data from its investigational BCL6 PROTAC® degrader ARV-393 at the European Hematology Association (EHA) 2024 Annual Congress that took place June 13-16, 2024 in Madrid, Spain, and presented new preclinical data from its PROTAC LRRK2 degrader program at the Biennial International LRRK2 Meeting that took place June 18-21, 2024 in Crete, Greece. Data presented at EHA showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma. “These new preclinical data for ARV-393 demonstrate that in these models it can effectively target and induce the degradation of the BCL6 protein that is commonly deregulated in DLBCL,” said John Houston, Ph.D., Chairperson, President, and Chief Executive Officer at Arvinas. “These encouraging results suggest that ARV-393 could be developed into a potential new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments." Preclinical data presented at the Biennial LRRK2 Meeting highlighted the potential of the company’s oral PROTAC LRRK2 degraders to treat neurodegenerative diseases. Preclinical studies in mice demonstrated full target engagement of LRRK2 kinase inhibitor and near-complete LRRK2 degradation with PROTAC LRRK2 degraders, but substantially less Type II pneumocyte enlargement compared to an experimental LRRK2 kinase inhibitor. In addition, the more noticeable Type II pneumocyte enlargement phenotype observed with the experimental LRRK2 kinase inhibitor was substantiated by the accumulation of surfactant protein C in lung, which was not observed after treatment with a PROTAC LRRK2 degrader. “Nonclinical findings presented this week suggest the potential for a wide therapeutic index and manageable safety pro PROTAC degraders versus experimental LRRK2 kinase inhibitors,” said Angela Cacace, Ph.D., Chief Scientific Officer at Arvinas. “In earlier preclinical studies, Arvinas’ PROTAC LRRK2 degraders have been shown to cross the blood-brain barrier and degrade LRRK2, a large multidomain scaffolding kinase, in deep brain regions.” Arvinas’ oral PROTAC BCL6 degrader ARV-393 is currently in a phase 1 clinical trial in patients with NHL, and Arvinas also has an oral PROTAC LRRK2 degrader, ARV-102, currently being investigated in a phase 1 clinical trial in healthy volunteers. About ARV-393 ARV-393 is an investigational PROTAC designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently in a phase 1 clinical trial in patients with non-Hodgkin lymphoma. About ARV-102 ARV-102 is an investigational PROTAC designed to degrade Leucine-rich repeat kinase 2 (LRRK2) which is a large multidomain scaffolding kinase. Human genetics, increased activity and expressions of LRRK2 is genetically involved in the pathogenesis of neurological diseases including Parkinson’s Disease and progressive supranuclear palsy. Arvinas is developing oral, blood-brain-barrier penetrant PROTAC degraders of LRRK2. About Arvinas Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis Targeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-102, targeting LRRK2 for neurodegenerative disorders; and ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit us on , which does not form part of this release, and connect with us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential for Arvinas’ investigational BCL6 PROTAC degrader ARV-393 as a new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments and its potential to address the traditional undruggable nature of BCL6; and the potential for Arvinas’ investigational PROTAC LRRK2 degraders (including ARV-102) to treat neurodegenerative diseases , and the potential for a wide therapeutic index and manageable safety profile. All statements, other than statements of historical facts, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: whether Arvinas will be able to successfully conduct and complete development for its product candidates, including ARV-393 and ARV-102, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials on its expected timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent other reports on the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. Contacts Investor Contact: Jeff Boyle, Arvinas Investor Relations +1 (347) 247-5089 Jeff.Boyle@arvinas.com Media Contact: Kirsten Owens, Arvinas Communications +1 (203) 584-0307 Kirsten.Owens@arvinas.com

– Proteomics analysis showed that rencofilstat improved aberrant protein profiles in IPF tissues – – Superior effects of rencofilstat alone and in combination with pirfenidone and nintedanib – EDISON, N.J., Sept. 14, 2023 (GLOBE NEWSWIRE) -- Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”), fibrotic diseases, hepatocellular carcinoma (“HCC”), and other chronic diseases, today announced positive results from a translational research study in which Hepion’s lead drug candidate, rencofilstat, was administered to diseased human lung tissue from patients with idiopathic pulmonary fibrosis (“IPF”). Proteomic quantitation of nearly 2,000 proteins showed that rencofilstat shifted protein profiles of IPF tissue towards normalized expression more robustly than the two standard-of-care drugs, nintedanib and pirfenidone, and with strong combinational effects especially when co-administered with nintedanib. In this study, FibroFind Ltd. (Newcastle, UK) obtained diseased lung tissue from two individuals undergoing lung transplantation for end-stage IPF, a deadly fibrotic lung disease. Precision cut lung slices (PCLuS) were made and individually incubated in culture with rencofilstat, nintedanib, pirfenidone, or combinations of the compounds for four days. Proteomics analyses were conducted on lung tissues at the end of treatment by PhenoSwitch Bioscience (Sherbrooke, Canada) and identified 1,953 unique proteins in the samples. The changes in abundance of the proteins produced by the drug treatments relative to vehicle control were determined and compared to abnormal protein profiles in IPF lungs reported in multiple proteomics studies over the past 5 years.1–3 These analyses demonstrated: Rencofilstat monotherapy altered levels of between 8 and 28% of the 1,953 proteins identified in PCLuS depending on dose and donor. This represented changes 2 - 4-times greater than nintedanib or pirfenidone in PCLuS from the first donor, and 2-fold greater than nintedanib in the second donor; Rencofilstat, in combination with nintedanib, altered levels of 16 - 42% of the 1,953 proteins depending on donor, which represented 2.7 - 7.8-fold more than nintedanib alone; Rencofilstat, in combination with pirfenidone, altered levels of 12 - 46% of the 1,953 proteins depending on donor, which represented 1.3 - 2.2-fold more proteins altered by pirfenidone alone; Among three studies reporting differentially expressed proteins in IPF lungs compared to normal controls,1–3 up to 41% of the reported differential proteins were also found in the current PCLuS study to be altered by rencofilstat alone or in combination. Furthermore, the majority of rencofilstat’s effects on the overlapping proteins (increased or decreased abundance) were opposite to the disturbances reported in the large IPF studies, which is consistent with disease-normalizing actions of rencofilstat; The normalizing actions of rencofilstat monotherapy and combinations spanned many important classes of proteins, including multiple isoforms of collagens, laminins, integrins, keratins, and MHC antigens. Additional, notable proteins whose abundance was positively shifted by rencofilstat included TIMP3, nidogen, surfactant protein C, cathepsin B, myeloperoxidase, lysozyme, mimecan, and asporin; and Cyclophilin B protein, a primary target of rencofilstat, was reported to be elevated in IPF lung tissue,1,2 suggesting a pathogenic role, and rencofilstat alone and in combination in PCLuS decreased tissue levels of cyclophilin B. “The technological advances in recent years in proteomics and other “omics” methodologies have blown the doors wide open on the scope and complexity of molecular changes in diseases like IPF, helping us to understand why so many narrowly targeted drug candidates have failed to have therapeutic effects,” commented Dr. Daren Ure, Hepion’s Chief Scientific Officer. “Rencofilstat’s suppression of fibrotic collagen production through cyclophilin B inhibition is one well-established mechanism, but inhibition of additional cyclophilin isoforms likely helps to explain rencofilstat’s robust effects in the present study. Rencofilstat alone shifted protein profiles more extensively than nintedanib and pirfenidone in most instances, and rencofilstat combinations were superior to every monotherapy, which is very encouraging. The old dogma in drug development about narrowly targeted drugs needs to adapt to emerging insights on complex diseases, and rencofilstat is one such candidate that is advancing that new paradigm of systems-targeting drug.” Dr. Robert Foster, Hepion’s CEO remarked, “As our Phase 2b NASH clinical trial progresses, we continue our nonclinical research on cancer and other fibrotic indications such as IPF with the aim of expanding our understanding of rencofilstat’s therapeutic and commercial potential. The new actions of rencofilstat that continue to be uncovered complement and strengthen the anti-fibrotic activities that we have seen in many experimental models of NASH, and the numerous positive outcomes in previous NASH clinical trials. The new findings in human IPF samples provide a good foundation for advancing rencofilstat in fibrotic diseases, which potentially also includes IPF.” REFERENCES 1. Konigsberg IR, Borie R, Walts AD, et al. Molecular Signatures of Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2021;65(4):430-441. doi:10.1165/RCMB.2020-0546OC 2. Tian Y, Li H, Gao Y, et al. Quantitative proteomic characterization of lung tissue in idiopathic pulmonary fibrosis. Clin Proteomics. 2019;16(1):1-11. doi:10.1186/S12014-019-9226-4 3. Åhrman E, Hallgren O, Malmström L, et al. Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. J Proteomics. 2018;189:23-33. doi:10.1016/J.JPROT.2018.02.027 About Hepion Pharmaceuticals The Company's lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental disease models and is currently in Phase 2 clinical development for the treatment of NASH. In November 2021, the U.S. Food and Drug Administration (“FDA”) granted Fast Track designation for rencofilstat for the treatment of NASH. That was followed in June 2022 by the FDA’s granting of Orphan Drug designation to rencofilstat for the treatment of HCC. Hepion has created a proprietary Artificial Intelligence deep machine learning (“AI/ML”) platform designed to better understand disease processes and identify patients that are rencofilstat responders. This AI/ML has the potential to shorten development timelines and increase the observable differences between placebo and treatment groups. In addition, Hepion’s AI/ML can be used to drive its ongoing NASH and HCC clinical development programs and identify other potential therapeutic indications for cyclophilin inhibition with rencofilstat. Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2021, and other periodic reports filed with the Securities and Exchange Commission. For further information, please contact: Stephen Kilmer Hepion Pharmaceuticals Investor Relations Direct: (646) 274-3580 skilmer@hepionpharma.com