CD163

Robust Dose-Dependent Target Engagement Demonstrated by Lixudebart in Both Studies Preliminary Evidence of Improvement in Organ Function: eGFR and Proteinuria in ANCA-RPGN, and ALT/AST in Liver Fibrosis Lixudebart Exhibited a Favorable Safety Profile and was Well-Tolerated BASEL, Switzerland I January 09, 2025 I Alentis Therapeutics (“Alentis”), a clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, announced positive topline results from two clinical trials of lixudebart (ALE.F02), a monoclonal antibody targeting Claudin-1 (CLDN1), developed to reverse organ fibrosis. Lixudebart was investigated in two double-blind, placebo-controlled, randomized studies. RENAL-F02 is an ongoing Phase 2 study in Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis (AAV) with Rapidly Progressive Glomerulonephritis (RPGN) ( NCT06047171 ), where 26 patients have been dosed for up to 24 weeks. FEGATO-01 is a Phase 1b clinical trial where 41 patients with mainly advanced F3/F4 liver fibrosis and/or mild cirrhosis were dosed for up to 4 weeks ( NCT05939947 ). “ The results from the two studies are very encouraging, particularly given the dose-dependent target engagement and favorable safety profile, ” said Luigi Manenti, Chief Medical Officer. “ We also observed an initial decrease in ALT/AST in liver fibrosis patients treated with lixudebart.” “Interim results from the RENAL-F02 study in ANCA-RPGN indicate beneficial effects of lixudebart on Glomerular Filtration Rate (GFR) recovery and proteinuria reduction,” said David Jayne, Professor of Clinical Autoimmunity at Cambridge University . “ These observations were further supported by reductions of CD163, a validated urinary biomarker, also indicating an impact on immune cell homing and trafficking to the kidney.” In both clinical trials, lixudebart demonstrated a favorable safety profile, both as a monotherapy and in combination with standard of care (n=51 active patients across the two trials). These findings are consistent with the safety results from the Phase 1 clinical trial of lixudebart in healthy volunteers (n=48 active patients). About Lixudebart (ALE.F02) Lixudebart is a first-in-class monoclonal antibody developed for liver, lung and kidney fibrosis. The investigational antibody is designed to reverse organ fibrosis by specifically targeting a unique CLDN1 epitope exposed in fibrotic tissue. In Phase 1 single- and multiple-ascending dose studies in healthy volunteers, lixudebart was well tolerated, with no serious safety concerns. Lixudebart has been granted Orphan Drug designation by the FDA for the treatment of Idiopathic Pulmonary Fibrosis (IPF). About Alentis Therapeutics Alentis Therapeutics is a clinical-stage biotechnology company pioneering first-in-class antibody-drug conjugates (ADCs) and antibodies targeting Claudin-1 (CLDN1) for oncology and multi-organ fibrosis. CLDN1 is a previously unexploited target that plays a key role in the pathology of cancer and fibrotic disease. Alentis is the leading company pioneering CLDN1 ADCs and antibodies to modify and reverse the course of select diseases. The FDA granted Fast Track designation to the lead ADC program, ALE.P02, for the treatment of advanced or metastatic CLDN1+ squamous cancers, irrespective of the organ of origin. Alentis was founded based on ground-breaking research in the laboratory of Prof. Thomas Baumert, MD at the University of Strasbourg and the French National Institute of Health and Medical Research (Inserm). Alentis is headquartered at the pharma-biotech hub in Basel, Switzerland, with an R&D subsidiary in Strasbourg, France, and clinical operations in the US. Visit www.alentis.ch SOURCE: Alentis Therapeutics

HOUSTON--( BUSINESS WIRE )-- Cellworks Group Inc. , a leader in Personalized Therapy Decision Support and Precision Drug Development, today announced results from a study demonstrating the efficacy of the Cellworks Therapy Response Index (TRI) combined with personalized tumor microenvironment (TME) modeling in predicting overall survival (OS) for non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). This comprehensive approach enables more precise identification of patient-specific dysregulation in immunotherapy signaling pathways, resulting in better predictions of treatment responses. Results from the study were showcased in a poster presentation titled, A Therapy Response Index Coupled with Personalized Tumor Microenvironment Modeling Predicts Overall Survival for Immunotherapy Treatment in NSCLC Patients , as part of the SITC 2024 Annual Meeting held in Houston, Texas from November 6-10, 2024. “In this study, we tackle one of the biggest challenges in cancer therapy today - accurately predicting how patients will respond to immunotherapy,” said Dr. James Wingrove , Vice President of Clinical Solutions at Cellworks and presenting author for the study. “Although immunotherapy has demonstrated significant success in treating NSCLC, existing tools for predicting individual patient outcomes are inadequate. This research marks a crucial step forward in understanding the intricate relationship between tumor genomics and the tumor microenvironment, paving the way for more personalized and effective treatment strategies.” “This study highlights Cellworks' commitment to advancing personalized oncology by providing tools that go beyond conventional prediction methods," said Dr. Michael Castro , Chief Medical Officer at Cellworks. “By integrating the Cellworks TRI score with detailed tumor microenvironment modeling, we’re able to offer a level of insight into immunotherapy outcomes that has the potential to transform how NSCLC patients are treated. This approach doesn’t just predict survival—it enables a deeper understanding of the unique cellular interactions within each patient's tumor, opening the door to more effective, personalized treatment strategies.” Study Design The study involved the development and validation of an algorithm to deconvolute cell proportion and cell-specific gene expression from bulk transcriptome data. Utilizing a reference matrix generated from single-cell NSCLC data (n=771,891 cells), the algorithm was applied to RNA-seq data from 63 NSCLC patients who had received immunotherapy. A personalized Computational Biosimulation Model (CBM) of tumor genomic networks was generated for each patient using whole exome sequencing data, and a Therapy Response Index (TRI) score was calculated. Study Results The tumor microenvironment composition significantly predicted overall survival in NSCLC patients, as shown in a Cox proportional hazards model (LR ꭓ² = 20.12, p-value = 7.29e-6, HR = 0.157). Combining the TRI score with tumor microenvironment cell proportions (TCP) further improved the model’s ability to predict OS (LR ꭓ² = 24.21, p-value = 8.63e-07, HR = 0.11). The study revealed specific immune markers correlated with improved outcomes, including the ratio of CXCL9+ M1-like macrophages to SPP1+ CD163+ M2-like macrophages, which positively correlated with longer survival. Patients with high interferon+ macrophages and higher activated CD8+ T cells also demonstrated better outcomes, while elevated neutrophil presence was associated with reduced survival. The Cellworks Platform, CBM and TRI The Cellworks Platform performs computational biosimulation of protein-protein interactions, enabling in silico modeling of tumor behavior using comprehensive genomic data. This allows for the evaluation of how personalized treatment strategies interact with the patient’s unique tumor network. Multi-omic data from an individual patient or cohort is used as input to the in silico Cellworks Computational Biology Model (CBM) to generate a personalized or cohort-specific disease model. The CBM is a highly curated mechanistic network of 6,000+ human genes, 30,000 molecular species and 600,000 molecular interactions. This model along with associated drug models are used to biosimulate the impact of specific compounds or combinations of drugs on the patient or cohort and produce therapy response predictions, which are statistically modeled to produce a qualitative Therapy Response Index (TRI) score, scaled from 0 (unfavorable outcome) to 100 (favorable outcome) for a specific therapy. The Cellworks CBM has been tested and applied against various clinical datasets with results provided in over 125 presentations and publications with global collaborators. About Cellworks Group Cellworks Group, Inc. is a leader in Personalized Therapy Decision Support and Precision Drug Development. The Cellworks Platform predicts therapy response for individual patients and patient cohorts using a breakthrough Computational Biology Model (CBM) and biosimulation technology. Backed by Artiman Ventures, Bering Capital, Sequoia Capital, UnitedHealth Group and Agilent Ventures, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers and software engineers working toward a common goal – attacking serious diseases to improve the lives of patients. The company is based in South San Francisco, California with a CLIA-certified computational laboratory in Franklin, Tennessee and a research and development facility in Bangalore, India. For more information, visit cellworks.life . All trademarks and registered trademarks in this document are the properties of their respective owners.

– In preclinical studies, CHS-1000 shows a high affinity for human ILT4, reverses ILT4-mediated immunosuppressive functions, leading to activation of immune cells and increased cytokine secretion – – Mechanism may enhance antitumor responses with immunotherapy – – First novel immuno-oncology product candidate discovered and developed by Coherus – – The CHS-1000 IND submission is planned for Q2 2024 – REDWOOD CITY, Calif., April 08, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today presented preclinical data for its immuno-oncology pipeline candidate, CHS-1000, a novel ILT4 monoclonal antibody, at the 2024 AACR Annual Meeting being held in San Diego, California. Data presented show CHS-1000 is a potent monoclonal antibody that binds selectively to human ILT4 (also known as LILRB2) with high affinity, efficiently blocking interaction with its ligands and reversing immunosuppressive functions, leading to activation of human dendritic cells and T cells and promoting polarization of macrophages to an inflammatory M1 phenotype. “Myeloid cell-mediated immunosuppression in the tumor microenvironment is a major contributor to tumor immune invasion and PD-1 resistance. The data presented in this poster demonstrate the potential for CHS-1000 to reverse myeloid suppression and activate an inflammatory immune response. Reprogramming myeloid cells in the tumor microenvironment holds promise as a new immuno-therapy approach with the aim to overcome resistance to I-O therapy and potentially provide benefit to more cancer patients,” said Theresa LaVallee, Ph.D., Chief Development Officer at Coherus. “CHS-1000 is our first internally discovered development candidate, and we are excited to be filing the IND this quarter. We plan to advance CHS-1000 into the clinic both as a single agent and in combination with LOQTORZI®.” These data will be presented today in a poster session, and the poster will be available for download at the time of the presentation: Abstract: 1364/15 Title: Characterization of CHS-1000, an Fc-modified anti-ILT4 monoclonal antibody for reprogramming suppressive myeloid cells in solid tumors Presenting author: Narendiran Rajasekaran, Ph.D. Session PO.IM01.02 – Immune Checkpoints and Inhibitory Molecules 1 Date and Time: Monday, April 8, 2024, 9:00 a.m. – 12:30 p.m. Pacific Daylight Time Poster data are summarized as follows: CHS-1000 binds specifically and selectively to human ILT4 (LILRB2) with high affinity and showed no cross-reactivity to other LILRB family members. CHS-1000 efficiently blocks the interaction of ILT4 with its ligands, HLA-A and HLA-G, and reverses ILT4-mediated immunosuppressive functions, leading to activation of M1 macrophages, dendritic cells, and T cells and increases in pro-inflammatory cytokine secretion in in vitro assays. CHS-1000 is Fc silent and lacks effector function activity in in vitro assays consistent with the engineered modification of the Fc region of the antibody. It also has IgG1‑like PK parameters in human FcRn transgenic mice. ILT4 and CD163, a marker of suppressive (M2) macrophages, are highly expressed in a broad range of solid tumors. About CHS-1000 Discovered and developed by Coherus, CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). CHS-1000 is designed to overcome myeloid cell-mediated immunosuppression and resistance in the tumor microenvironment. In preclinical studies, CHS-1000 promotes repolarization of suppressive M2 macrophages to a pro-inflammatory M1 phenotype and enhances activation of dendritic cells and T cells in vitro. Coherus plans to investigational new drug (IND) application in Q2 2024 and begin clinical studies later this year. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on researching, developing, and commercializing innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will synergize with its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel anti-IL-27 antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, ADCC-enhanced anti-CCR8 antibody currently in a Phase 1/2 study as a monotherapy in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4, with an IND filing planned in Q2 2024. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, and YUSIMRY® (adalimumab-aqvh), a biosimilar of Humira®. Neulasta® is a registered trademark of Amgen, Inc. Humira® is a registered trademark of AbbVie Inc. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to identify synergies between its I-O pipeline and its commercial capabilities; Coherus’ expected timing for filing an IND for CHS-1000; Coherus’ expectations to be able to advance its candidates through clinical trials; and Coherus’ expectations that its immunotherapy candidates will enhance outcomes for patients with cancer. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance, or achievements to differ significantly from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the preclinical and clinical drug development process; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ competitive position; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risks of competition; the risk that Coherus is unable to complete commercial transactions; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the Securities and Exchange Commission on March 15, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission. UDENYCA®, YUSIMRY®, and LOQTORZI®, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Coherus Contact Information: For Investors: Jami Taylor Head of Investor Relations IR@coherus.com For Media: Jodi Sievers VP, Corporate Communications media@coherus.com