CD59

We are delighted to announce that we have been selected for an oral presentation at the 37th European Immunogenetics and Histocompatibility (EFI) Conference! The presentation has been made May 21th by Séverine Planel. Title of the talk was: Humoral response in lung cancer patients treated with a plasmacytoid dendritic allogeneic cell line-based cancer vaccine. Using an antibody-mediated complement-dependent cytotoxicity (CDC) assay in flow cytometry using healthy donor’s or patient’s sera, we have shown that PDC*line cells were resistant to the complement dependent killing mediated by patient’s anti-HLA Ab despite the functionality of the patient’s complement system. Interestingly, we have shown that PDC*line cells express high level of membrane-bound complement regulatory proteins (mCRPs: CD46, CD55, and CD59) render them resistant to Ab-mediated CDC as shown by experiments using blocking Ab. Altogether, these results show the innocuity and the absence of deleterious effect of anti-HLA Ab on PDC*line cells used as a cancer vaccine platform. Abstract of the presentation is available through this link: /sites/default/files/images/ABSTRACT%20EFI%202024_vFinal.pdf About the event: The conference is the annual event of the European Federation of Immunogenetics (EFI). It has been held in Geneva, Switzerland from 20 - 23 May 2024. hashtag

– Significant advancements in engineering neutralizing antibody (NAb) evasion properties into receptor-targeted capsids, including novel TfR1-binding capsids, demonstrate increased opportunities to treat AAV seropositive patients – Disclosed multiple families of capsids targeting two novel proteins – CA4 and CD59; capsids binding human CA4 cross the blood-brain barrier in humanized mice, while capsids that cross react with human and non-human primate CD59 demonstrate enhanced tropism for the Central Nervous System (CNS) and skeletal muscle NEW YORK, May 10, 2024 (GLOBE NEWSWIRE) -- Apertura Gene Therapy, a biotechnology company widening the aperture of gene therapy opportunities for treating debilitating diseases, showcased significant advancements in its capsid engineering platform during several presentations at the 27th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). Scientists from the lab of academic collaborator and scientific co-founder, Ben Deverman, Ph.D., Senior Director of Vector Engineering and Institute Scientist at the Broad Institute of MIT and Harvard, presented new data showcasing the progress made in engineering neutralizing antibody (NAb) evasion attributes into the company’s novel, human-receptor targeted capsids and disclosed two newly identified families of capsids targeting human CA4 and CD59. “The progress regarding human CA4, CD59 and NAb-evading capsids presented by the lab of Apertura collaborator and scientific co-founder, Dr. Ben Deverman, support our position as the leader in receptor-mediated capsid engineering and validate our strategy to advance our internal CNS programs utilizing better gene therapy delivery vehicles that are human-centric blood brain barrier crossing capsids. We look forward to advancing our first program toward an IND submission next year,” said Joseph La Barge, Chief Executive Officer of Apertura. “Our proven ability to engineer NAb-evading attributes into our TfR1 and other receptor targeting capsids opens new opportunities to treat more patients who otherwise would not be eligible for gene therapy clinical trials or treatments.” The presence of anti-AAV NAbs at even low levels has been repeatedly shown to lower therapeutic levels of transgene expression and has long been a challenge in the gene therapy field. The presence of pre-existing NAbs across the population has limited the eligible patient population for clinical trials and addressable patient population for commercial products. Apertura’s capsid engine has yielded novel capsids that have demonstrated NAb-evading properties while maintaining the full engineered tropism of the capsid. Specifically, the data show that the latest TfR1-binding capsids are not neutralized below 50% activity (when diluted at 1:4) in a subset of sera that are neutralizing to AAV9, AAV5 and the TfR1 binding capsids without antibody evading mutations. Data from the company’s ongoing preclinical studies support the premise that subsets of patients with pre-existing NAbs, who would otherwise be excluded from treatment, could be dosed with its novel, NAb-evading capsids. The CD59 receptor is a GPI-anchored protein and member of the Ly6 family that is broadly expressed across the human body. Apertura’s novel capsids, engineered with the company’s proprietary, mechanism-of-action focused engine, have demonstrated through in-vitro and in-vivo studies efficient gene delivery to the brain, spinal cord and skeletal muscle, while de-targeting the liver, opening up significant opportunities for addressing neuromuscular and lysosomal storage disorders. These capsids have also shown to cross react with non-human primate CD59. Carbonic anhydrase IV (CA4) is a GPI-anchored enzyme highly expressed on endothelial cells across the blood-brain barrier. These proprietary, engineered capsids effectively cross the blood brain barrier in mice modified to express the human receptor and transduce multiple cell types across the CNS with high efficiency. The oral presentations and posters presented at ASGCT can be viewed here. Presentation details Presentation: Second Generation AAV Capsids Reprogrammed to Bind Human Transferrin Receptor are Targeted to the Brain and De-targeted from the Liver in human TFRC Knock-in Mice (#120)Presenter: Ken Chan, PhD, Broad Institute of MIT and Harvard Presentation: An AAV Capsid Programmed to Bind a Broadly Expressed Human Receptor Mediates Enhanced Gene Delivery to the CNS and Skeletal Muscle in vivo (#217)Presenter: Jason Wu, PhD, Broad Institute of MIT and Harvard Poster: Human CA4-Targeting AAV Capsids Efficiently Transduce the CNS in Humanized Mice (#991)Presenters: Nuria Roxana Botticello-Romero, Jason Wu, Qin Huang, Thomas Beddow, Ken Y. Chan, Pamela Brauer, Fatma Elzahraa Eid, Alina Chan, Benjamin E. Deverman Poster: Engineering Human CNS Receptor-Targeted Capsids for Improved Antibody Evasion (#1551)Presenters: Simon Pacouret, William Donahoe, John W. Harvey, Pamela P. Brauer, Qingxia Zheng, Chin-Yen Lin, Binhui Zhao, Gabrielle Clouse, Qin Huang, Jencilin Johnson, Casey Keyes, Catherine P. Pirtle, Jarrett Rios, Albert T. Chen, Fatma Elzahraa Eid, Andrew J. Barry, Yujia A. Chan, Ken Y. Chan, Benjamin E. Deverman, Poster: Benchmarking natural and synthetic AAV capsids for neutralizing antibody evasion (#1553)Presenters: William Donahoe, Simon Pacouret, Pamela P. Brauer, John W. Harvey, Catherine P. Pirtle, Ken Y. Chan, Yujia A. Chan, Benjamin E. Deverman About Apertura Gene TherapyApertura Gene Therapy is a biotechnology company unlocking new opportunities for treating currently intractable diseases. The company is uniquely positioned to develop genetic medicines by simultaneously engineering AAV capsids, genetic regulatory elements and payloads to overcome limitations in cellular access, gene expression, pre-existing immunity and manufacturability. Apertura is advancing an internal pipeline of programs targeting undisclosed central nervous system disorders utilizing its novel capsids and plans to submit an Investigational New Drug (IND) application for its first product candidate in 2025. Founded in 2021 on technologies from the Broad Institute and Harvard Medical School, and with support from Deerfield Management Company, the company is based in New York City. For more information, please visit our website at www.aperturagtx.com and follow us on LinkedIn. Contacts: Investorsinvestors@aperturatx.com Mediamedia@aperturatx.com

SEATTLE--( BUSINESS WIRE )--Omeros Corporation (Nasdaq: OMER) today announced that the slides presented yesterday in the “late-breaker” session at the 2023 European Hematology Association (EHA) Congress in Frankfurt, Germany are now available on Omeros’ website . The presentation, which details data from a pre-specified interim analysis from the ongoing Phase 1b clinical trial of Omeros’ lead MASP-3 inhibitor OMS906 in complement-inhibitor-naïve adults with paroxysmal nocturnal hemoglobinuria (PNH), was identified by EHA’s Scientific Program Committee as one of the top five late-breaking submissions and selected for oral presentation. The presentation, entitled OMS906, A mannan-binding lectin-associated serine protease-3 (MASP-3) Inhibitor, Normalizes Hemoglobin Levels in Treatment-naïve PNH Patients: Interim Data from a Proof-of-Concept Clinical Trial, was delivered to a large audience by Jens Panse, MD, Senior Physician and Deputy Director of the Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, and Managing Medical Director of the Center for Integrated Oncology, Aachen, Germany. Also available on Omeros’ website is a second presentation at EHA – Alternative Pathway MASP-3 Inhibitor OMS906: Results from a First-in-Man Phase 1 Study in Healthy Subjects and Study Design of Two Ongoing Clinical Trials in Patients with PNH – by Morag Griffin, MBChB, FRCPath, Consultant in Haematology of St. James University Teaching Hospital, Leeds, United Kingdom. This poster presentation describes findings from a single-ascending dose study evaluating OMS906 safety, pharmacokinetics and pharmacodynamics in healthy subjects. About PNH Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening acquired disorder that causes production of red blood cells lacking certain surface proteins (CD55 and CD59), making them vulnerable to destruction by the complement system. This leads to intravascular hemolysis (destruction of red blood cells within blood vessels) and extravascular hemolysis (when damaged red blood cells are removed by macrophages in the spleen or liver). Left untreated, PNH is associated with debilitating anemia, a high risk of thrombosis, fatigue, and a severely reduced survival rate. There remains a significant unmet need for PNH therapies, as a large proportion of patients treated with C5 inhibitors continue to experience hemolysis and approximately one third of them still require red blood cell transfusions. About OMS906 OMS906 is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the key activator of the complement system’s alternative pathway. The complement system plays a central role in inflammation and becomes activated as a result of tissue damage or microbial infection. Responsible for the conversion of pro-complement factor D to complement factor D, MASP-3 is believed to be the premier target in the alternative pathway. MASP-3 has the lowest native circulating level and low relative clearance compared to the other alternative pathway proteins and, unlike C5 and C3 blockers, MASP-3 inhibition leaves intact the lytic arm of the classical pathway, important for fighting infection. Also, unlike other components of the alternative pathway, MASP-3 is believed not to be an acute phase reactant, which could provide a significant advantage to MASP-3 inhibitors, like OMS906, over other alternative pathway inhibitors. MASP-3 inhibitors are thought to have preventive or therapeutic effects across a broad range of diseases including PNH, hemolytic uremic syndrome (HUS), atypical HUS, traumatic brain injury, arthritis, wet age-related macular degeneration, ischemia-reperfusion injury, transplant-related complications and other immune-related disorders. Through its growing and exclusive intellectual property position, Omeros controls the use of MASP-3 inhibitors across a wide range of alternative pathway-related and other diseases and disorders. About Omeros Corporation Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders. Omeros’ lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application pending before FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). Narsoplimab is also in multiple late-stage clinical development programs focused on other complement-mediated disorders, including IgA nephropathy, COVID-19, and atypical hemolytic uremic syndrome. Omeros’ long-acting MASP-2 inhibitor OMS1029 is currently in a Phase 1 clinical trial. OMS906, Omeros’ inhibitor of MASP-3, the key activator of the alternative pathway of complement, is advancing across multiple clinical programs for alternative pathway-related diseases, including paroxysmal nocturnal hemoglobinuria (PNH) and complement 3 (C3) glomerulopathy. For more information about Omeros and its programs, visit www.omeros.com .