Apertura Gene Therapy Showcases Advancements in Capsid Engineering Platform in Presentations at ASGCT Annual Meeting
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May 10, 2024
Apertura Gene Therapy Showcases Advancements in Capsid Engineering Platform in Presentations at ASGCT Annual Meeting

– 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 – 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 humancentric 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 E[iciently 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 Therapy 

Apertura 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, preexisting 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.

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Andrew Steinsapir

Acting Chief Technology Officer

Andrew Steinsapir is the Acting Chief Technology Officer of Apertura Gene Therapy and a Director, Gene Therapy Program Lead of Deerfield Management’s Discovery and Development team. Prior to joining Deerfield in 2021, Mr. Steinsapir was a Consultant for over three years at Dark Horse Consulting Group, where he provided strategic and tactical support for more than 30 cell and gene therapy firms, pharma, and investment firms. Previous to Dark Horse, Mr. Steinsapir worked at 4D Molecular Therapeutics for over three years, holding various positions, with his most recent role being Senior Process Development Associate I. Mr. Steinsapir holds a BS in Chemical Engineering with an emphasis on Biotechnology from the University of California, Berkeley.

Juliana Leung, PhD

The Broad Institute

Juliana Leung, PhD, is the Senior Director of Business Development and Licensing Transactions at the Broad Institute of MIT and Harvard, where she leads Broad’s business development and licensing team. She has more than 15 years of business development and transactional experience. Juliana provides expertise to build collaborations with industry as well as partnerships with pharma, biotech, and venture groups that are eager to translate technologies into products that can benefit patients, the research community, and improve human health.

Before joining the Broad in 2012, Juliana was Senior Business Strategy and Licensing Manager for Research Ventures and Licensing at Partners Healthcare, now referred to as Innovation at MassGeneral Brigham. She received her SB in Biology from MIT and her PhD in Cellular, Molecular and Biophysical Studies from Columbia University in New York.

Ben Deverman, PhD

Senior Director of Vector Engineering at the Broad Institute of MIT and Harvard

Ben Deverman is the Senior Director of Vector Engineering and an Institute Scientist at the Broad Institute of MIT and Harvard. Ben’s laboratory in the Stanley Center for Psychiatric Research at the Broad Institute develops and applies novel high-throughput screens and data-driven protein and genome engineering techniques to create more efficient and targeted AAV vectors to advance gene therapy and support scientific discovery. In prior work at the California Institute of Technology, Ben and colleagues identified numerous capsids, including AAV-PHP.B and an enhanced variant, AAV-PHP.eB, that made efficient brain-wide gene delivery possible for the first time. Ben earned a PhD in Molecular Cell Biology from Washington University and was trained as a postdoc in neuroscience at the California Institute of Technology.

Michael Greenberg, PhD

Chair of the Department of Neurobiology and the Nathan Marsh Pusey Professor of Neurobiology at Harvard Medical School

Dr. Greenberg received his PhD from The Rockefeller University in 1982 and carried out his postdoctoral research at New York University Medical Center. After joining the faculty at Harvard Medical School in 1986, Dr. Greenberg served first as the founding Director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and since 2008 as Chair of the Department of Neurobiology at Harvard Medical School.

Joseph La Barge

Apertura Gene Therapy

Joseph La Barge is CEO and serves on the Board of Managers of Apertura Gene Therapy. Previously, Mr. La Barge was an executive at Spark Therapeutics, Inc., serving as Chief Business Officer from 2019 to 2021 and as Chief Legal Officer from 2013 to 2019. In these roles, he oversaw many areas of company growth, including business development, patient advocacy, quality assurance, legal affairs, compliance, finance, public policy and global pricing and reimbursement, growing the company to 830 employees over eight years. He led the negotiation of Spark’s acquisition by Roche, raised more than $1 billion in capital from private and public financings and oversaw the in-license of numerous product candidates and platform technologies. Mr. La Barge also managed the acquisition and construction of Spark’s initial 180,000 square feet office and laboratory space, including GMP suites, to manufacture the global supply of Luxturna. Prior to Spark, Mr. La Barge served as Vice President, General Counsel & Secretary, Chief Compliance Officer at Tengion, Inc., where he was responsible for managing legal affairs, compliance and quality assurance. Mr. La Barge has served as a Member of the American Society of Gene & Cell Therapy Government Affairs Committee. He earned his BA in Education and Psychology at Bucknell University and his JD at Temple University James E. Beasley School of Law.

David Greenwald, PhD

Deerfield Management Company

Dave serves on the Board of Managers of Apertura Gene Therapy.

Dr. Greenwald was a Howard Hughes Medical Institute research fellow while earning a BS in Cellular Biology and Molecular Genetics from the University of Maryland, College Park and earned his PhD in Genetics from Tufts University. Dr. Greenwald currently serves on the Boards of Jaguar Gene Therapy, Axovia Therapeutics, and Apertura Gene Therapy, and has worked at Deerfield Management since 2018.

Elise Wang

Deerfield Management Company

Ms. Wang is a Partner and Head of Private Equity Capital Markets on the Public Structured Finance team at Deerfield Management and joined the Firm in 2010. Ms. Wang provides extensive research and analysis on individual companies operating in the healthcare industry in both the US and Europe.

Ms. Wang is a board member of Jaguar Gene Therapy. Prior to Deerfield, Ms. Wang was a Senior Research Analyst and Managing Director covering the biotechnology sector at PaineWebber and Citigroup. She began her career in healthcare as a venture capitalist and banker at PaineWebber and was an officer of PaineWebber Development Corporation, which managed nearly $1 billion in assets representing three PaineWebber funds and several research and development limited partnerships (RDLPs) invested in biotechnology and high technology companies.

Ms. Wang holds an AB in Engineering Sciences with a specialty in Biomechanics from Harvard University and an MBA from Harvard Business School.

Jonathan Leff

Deerfield Management Company

Mr. Leff is a Partner on the Therapeutics team at Deerfield Management since 2013 and Chairman of the Deerfield Institute. He focuses on venture capital and structured investments in biotechnology and pharmaceuticals. Prior to Deerfield, for more than sixteen years, Mr. Leff was with Warburg Pincus, where he led the firm’s investment efforts in biotechnology and pharmaceuticals. He is a member of the Boards of several private healthcare companies as well as several not-for-profit Boards, including the Spinal Muscular Atrophy Foundation, Friends of Cancer Research, Reagan-Udall Foundation for the Food and Drug Administration and the Columbia University Medical Center Board of Advisors. Mr. Leff has also been active in public policy discussions related to healthcare and medical innovation. He previously served as a member of the Executive Committee of the Board of the National Venture Capital Association (NVCA), where he led NVCA’s life sciences industry efforts as Chair of NVCA’s Medical Innovation and Competitiveness Coalition (NVCA-MedIC), and also previously served on the Board of the Biotechnology Innovation Organization. Mr. Leff holds an AB from Harvard University and an MBA from Stanford University’s Graduate School of Business.

Roberto Pastrano

Vice President of Finance and Operations

Roberto Pastrano is Vice President of Finance and Operations at Apertura Gene Therapy. With over 17 years of Biotechnology and Pharmaceutical experience in finance, accounting, and operations, Mr. Pastrano oversees Apertura’s operations, IT, finance and accounting functions. Previously, Mr. Pastrano served as Senior Director and Corporate Controller at Day One Biopharmaceuticals, a biotechnology company focused on pediatric cancers, where he led the accounting, procurement, and IT functions. Prior to Day One, he spent six years at Loxo Oncology at Lilly, formerly Loxo Oncology, as Senior Director of Finance where he led the accounting, finance, procurement, and legal functions after joining the company as an Assistant Controller in August 2015. Notably, while at Loxo Oncology at Lilly, Mr. Pastrano played a key role in the development of Vitrakvi (larotrectinib), the second tissue agnostic FDA-approved drug for adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion & Retevmo (selpercatinib), the first FDA-approved therapy for patients with lung and thyroid cancers with RET gene alterations, which was approved under the FDA’s Accelerated Approval pathway with an orphan drug designation. Mr. Pastrano holds a BS in Accounting from the City University of New York – Herbert H. Lehman College and an MBA with a concentration in Finance.

Jordan Dubow, MD

Acting Chief Medical Officer

Dr. Jordan Dubow is the Acting Chief Medical Officer of Apertura Gene Therapy. Dr Dubow is a neurologist with fellowship training in movement disorders and vascular neurology and began his medial career in academia as a movement disorders and stroke neurologist. Dr. Dubow has extensive experience in the pharmaceutical and biotech industry, where he has served in full time and acting CMO capacities for both pubic and private companies, leading all clinical and regulatory aspects of development for small and large molecule drugs and cell and gene therapies. Dr. Dubow received his medical degree from the Northwestern University Feinberg School of Medicine. He completed his internal medicine internship, Neurology residency and fellowship training at University of California Los Angeles, Northwestern University and Weill Cornell Medical College.

Jenna Heyman

Head of Human Resources, Vice President

Jenna Heyman joined Apertura Gene Therapy as Vice President and Head of Human Resources, bringing more than a decade of experience in Human Resources, as well as exceptional knowledge of building strong high performing teams in the biotechnology and CDMO industry. In her previous role as Vice President of Human Resources at Recipharm, Ms. Heyman oversaw HR for Arranta Bio and Vibalogics, and was instrumental in helping execute a global growth strategy. There, she was responsible for all operational and strategic activity in HR, including the areas of talent acquisition and retention, benefits and compensation, employee development and growth and corporate culture. Prior, Ms. Heyman served in progressive leadership positions at Brammer Bio, which was acquired by Thermo Fisher Scientific. Ms. Heyman has a BA in Psychology and an MA in Education from Quinnipiac University. She also holds a SHRM-SCP (Society of HR Management – Senior Certified Professional) certification.

Diego Garzón, PhD

Vice President of Corporate Development

Dr. Diego Garzón is Vice President of Corporate Development at Apertura Gene Therapy and has more than 16 years of biotechnology and pharmaceutical sector experience within the U.S. and internationally, with a background spanning commercial R&D and Business Development. Dr. Garzón brings extensive knowledge of multiple therapeutic areas and provides leadership in the areas of managing teams and portfolio execution, having previously brought seven medicines to the market. Prior to joining Apertura, Dr. Garzón held roles at Exicure, Allergan, BMS and Schering-Plough. He most recently served as Vice President, Corporate Development and Strategy at Exicure. Dr. Garzón received his BSc in Biology at the University of Waterloo, PhD in Neuroscience at McMaster University and MBA degrees from Queen’s University and Cornell University.

Sisi Chen, PhD

Senior Director of Platform Technology

Dr. Sisi Chen is  Senior Director of Platform Technology at Apertura Gene Therapy, where she and her teams are harnessing the power of machine learning and high-throughput experimentation to engineer better payloads and capsids for gene therapies. She brings over 15 years of research experience in technology development in the areas of functional and single-cell genomics, computational biology, and stem cell biology.Prior to Apertura, she served as the Director of the Beckman Single-cell Profiling and Engineering Center (SPEC) at Caltech, where she led a cross-functional computational and experimental team to leverage the power of single-cell genomics towards applications in therapeutic screening and cell engineering. Her work at SPEC on performing large-scale analyses of immune cell responses to small molecule drugs was awarded the Society of Laboratory Automation and Sciences (SLAS) 2021 Innovation Award. Dr. Chen earned a B.S. in Electrical engineering from MIT and a Ph.D. in Bioengineering from the University of California Berkeley.

Jorge Santiago-Ortiz, PhD

Senior Director of Chemistry, Manufacturing, and Controls (CMC)

Dr. Jorge Santiago-Ortiz is the Senior Director of Chemistry, Manufacturing, and Controls (CMC) at Apertura Gene Therapy. He is a chemical engineer with a background in bioprocess engineering, molecular biology, and biochemistry and a focus in gene therapy and process development. Born and raised in Puerto Rico, Jorge completed his bachelor’s degree in Chemical Engineering with a Biotechnology Certificate in 2010 at the University of Puerto Rico, Mayagüez; as an undergraduate student, he conducted research in biochemistry under Dr. Belinda Pastrana-Rios, where he worked on protein expression, purification, and characterization. In 2016, Jorge completed a Ph.D. in Chemical and Biomolecular Engineering with a minor in Molecular and Cell Biology at the University of California, Berkeley. Working in Dr. David Schaffer’s laboratory, his Ph.D. dissertation work focused on the engineering of lentiviral and adeno-associated virus (AAV) vectors for gene therapy applications using in vitro and in vivo directed evolution. Following the completion of his Ph.D., Jorge transitioned to an industry role at BioConsortia Inc. (Davis, CA), where he led the fermentation and scale-up of beneficial plant-associated microbes for enhanced crop yields and improved plant health. Prior to his current role at Apertura, Jorge worked as the Sr. Director of Process Development at BioCentriq, a gene and cell therapy contract development and manufacturing organization (CDMO) based in Newark, NJ, where he oversaw process development for gene and cell therapy clinical products and managed gene therapy projects. Jorge is an active member of the Society for Advancement of Chicanos/Hispanics & Native Americans in Science (SACNAS), and he also serves on the National Academies for Sciences, Engineering, and Medicine’s Standing Committee on Biotechnology Capabilities and National Security Needs and in the American Society of Gene and Cell Therapy’s Diversity, Equity, and Inclusion (DEI) Committee.

Apertura Benefits
Flexible Time Off
Medical, Dental, Vision
401K
Equity
And more!

David Tischler

Strategy & Operations Consultant

David Tischler is an Advisor to Apertura Gene Therapy leveraging a background focused on building and financing companies to commercialize life science innovations. Currently, he is engaged by venture capital firms and their therapeutics and bioengineering-focused portfolio companies to lead operations, business development, fundraising, and strategic commercialization projects. Most recently, David was the co-founder and CEO of ZetaGen Therapeutics, an early-stage life science company developing targeted local therapies for large unmet needs in the regenerative medicine and oncology markets. Prior to ZetaGen, David was a product manager at Castlight Health (NYSE: CSLT), where he helped launch Action, an artificial intelligence product that uses machine learning to manage the health of employee populations of Fortune 100 companies. David also served as acting CEO of DigiSight Technologies (now Verana Health), a venture-backed company that leverages large datasets to manage retinal diseases. Previously, served as the due diligence chair for Mass Medical Angels, a life science-focused angel investment group and also worked as an associate at Venzyme Venture Catalyst where he turned early-stage life science technologies from academic institutions into financeable companies. David has a BS in Biology from the University of Michigan and an MBA from the UC Berkeley-Haas School of Business.

Joseph La Barge

Chief Executive Officer

Joseph La Barge is CEO and serves on the Board of Managers of Apertura Gene Therapy. Previously, Mr. La Barge was an executive at Spark Therapeutics, Inc., serving as Chief Business Officer from 2019 to 2021 and as Chief Legal Officer from 2013 to 2019. In these roles, he oversaw many areas of company growth, including business development, patient advocacy, quality assurance, legal affairs, compliance, finance, public policy and global pricing and reimbursement, growing the company to 830 employees over eight years. He led the negotiation of Spark’s acquisition by Roche, raised more than $1 billion in capital from private and public financings and oversaw the in-license of numerous product candidates and platform technologies. Mr. La Barge also managed the acquisition and construction of Spark’s initial 180,000 square feet office and laboratory space, including GMP suites, to manufacture the global supply of Luxturna. Prior to Spark, Mr. La Barge served as Vice President, General Counsel & Secretary, Chief Compliance Officer at Tengion, Inc., where he was responsible for managing legal affairs, compliance and quality assurance. Mr. La Barge has served as a Member of the American Society of Gene & Cell Therapy Government Affairs Committee. He earned his BA in Education and Psychology at Bucknell University and his JD at Temple University James E. Beasley School of Law.