CA4

– 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