Glycogen Storage Disease Type III

As several well-funded companies race to make generative AI models that can design new protein therapies from scratch , one small startup has found a new use for existing AI systems: compressing large proteins to better package them in gene therapies or deliver them to hard-to-reach places like the back of the eye. The startup, called ZipBio, has raised $4 million in seed funding for the idea, it told Endpoints News exclusively. “The inspiration came from the compression of technology in the digital world,” CEO Roee Farber said in an interview. Of course, shrinking the structure of a protein and retaining its function isn’t as simple as compressing digital documents into a zip file. The startup is trying to isolate small parts of proteins that are most important for making a drug and shave off the rest. The problem is that the rest of the protein is there for a reason. Removing it can cause the entire thing to collapse. ZipBio’s solution is to use generative AI to create a new backbone that holds that key part of the protein in place. “In the past, nobody succeeded with that. Now it’s something we can do relatively trivially,” Farber said. The company hasn’t published details about how its approach works, but Farber said ZipBio is using and refining publicly available AI models for protein design, rather than creating its own. The startup was founded in 2023, began work on its lead drug just eight months ago, and is already testing it in animals, Farber said. That drug candidate builds on Regeneron’s antibody Eylea as a starting point — an eye therapy that made the company $5.89 billion last year. Eylea inhibits two forms of VEGF, a protein that can spur unwanted blood vessel growth in the eyes. But just blocking the A and B forms of the protein doesn’t fully treat everyone. ZipBio has created a compact inhibitor of VEGF-C and VEGF-D and meshed it with Eylea, using AI to create a hybrid molecule that Farber says is compact enough to travel to the back of the eye, something that a simple fusion of two full antibodies likely wouldn’t do. Clinical trials could begin as soon as 2026. The startup is also working with the French nonprofit Généthon to create a compact version of a protein that’s too big to fit into AAVs — the most common viral vectors used in gene therapy — to treat a rare disease called glycogen storage disorder III, a form of muscular dystrophy. ZipBio’s seed funding was led by NFX, a venture capital firm that invests in tech startups at a seed stage or earlier. MoreVC, which focuses on early-stage Israeli tech startups, also contributed. ZipBio’s team of 12 is currently split between Seattle and Tel Aviv, Israel.

HYOGO, Japan--( BUSINESS WIRE )-- JCR Pharmaceuticals Co., Ltd. (TSE 4552; Chairman and President: Shin Ashida; “JCR”) announced today the completion of the regulatory review by the Pharmaceuticals and Medical Devices Agency (PMDA) for the clinical trial notification for the Phase I study of JR-441 in individuals with mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome type A). JR-441 is a recombinant form of heparan N-sulfatase that is developed using JCR’s proprietary J-Brain Cargo ® blood-brain barrier (BBB)-penetrating technology. JR-441 addresses a significant unmet medical need by crossing the BBB and targeting the neurological symptoms of MPS IIIA within the central nervous system. "MPS IIIA is a rare and life-threatening lysosomal storage disorder for which there are currently no approved treatment options for individuals living with this devastating disease, and there is a dire need to address the neurological signs and symptoms of MPS IIIA,” said Shin Ashida, Chairman and President of JCR Pharmaceuticals. “We are pleased that the PMDA’s review of the Phase I study plan is complete, and that clinical development program is progressing. We are committed to continuing to advance the JR-441 clinical development program with the goal of meeting the unmet medical needs of this patient community. We look forward to sharing updates on the program when they are available.” The European Commission (EC) and the U.S. Food and Drug Administration (FDA) granted JR-441 orphan drug designation (ODD) for the treatment of MPS IIIA. JR-441 is currently being studied in an ongoing Phase I/II clinical trial in Germany (JR-441-101, NCT06095388 ), apart from this Japanese Phase I study. The impact of this announcement on JCR's consolidated financial results for this fiscal year (ending March 2025) is expected to be minor. About Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is an autosomal recessive disease caused by pathogenic mutations in the SGSH gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. The accumulation of heparan sulfate in several types of cells of the body, especially in the central nervous system in the brain, results in severe neurological deterioration, cognitive impairment, mild somatic involvement, and shortened lifespan. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients. For more information, please visit https://www.jcrpharm.co.jp/en/site/en/ . Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

Genethon is a leader in developing gene therapies for rare and ultra-rare diseases PARIS, FRANCE (May 10, 2023) – Genethon, a unique non-profit gene therapy R&D, announced today its research will be featured in 4 oral presentations and 10 posters at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), May 16-20, 2023, at the Los Angeles Convention Center in Los Angeles, CA. The international convention attracts thousands of scientists, physicians, patient advocates and government officials. “We are proud to report some of our most recent progress, covering the advancement of novel gene therapy candidates for multiple rare genetic diseases, and the design of novel vectors and tools,” said Frederic Revah, Genethon CEO. “The objective of Genethon’ scientists is to pursue research of excellence allowing more and more patients with rare genetic diseases to benefit from the treatments they need.” Genethon’s Ana Buj Bello, M.D., Ph.D., MBA, leader of the Neuromuscular Diseases and Gene Therapy Team, is co-chair of the oral abstract session on AAV Vectors – Clinical/Nonhuman primate studies, Wednesday, May 17, 3:45 pm – 5:30 pm US PDT (Rm 411). Dr. Buj Bello also is presenting a poster titled, AAV-mediated gene therapy corrects the severe phenotype of acid ceramidase deficient mice (Board No. 15918), Friday, May 19, 12 pm – 2 pm US PDT. Genethon has four scientists participating in the following oral poster presentation sessions (all times are US PDT): Wednesday, May 17 AAV Vectors – Preclinical and Proof-of-Concept In Vivo Studies I (3:45 pm – 5:30 pm) Rm 408 AB More Than Nine Year Survival of a GRMD Dog after Injection of AAV-Microdystrophin Gene Therapy (4:15 pm – 4:30 pm) – Caroline Le Guiner Thursday, May 18 Metabolic, Storage, Endocrine, Liver and Gastrointestinal Diseases I (1:30 pm to 3:15 pm) Rm 403 AB Single AAV vector gene therapy with a mini-GDE transgene corrects muscle impairment in mouse, rat and human cellular models of glycogen storage disease Type III (3 pm – 3:15 pm) – Antoine Gardin Novel Genetic Approaches for Muscle Diseases (3:35 pm – 5:30 pm) Rm 408 AB Development of MYOrganoids for therapeutic evaluation of gene therapy product in Duchenne Muscular Dystrophy (4:30 pm – 4:45 pm) – Laura Palmieri Saturday, May 20 AAV Development for Eye, Muscle, Kidney and CNS (8 am – 9:45 am) Concourse Hall 150 & 151) An integrin-targeting AAV developed by a novel computational rational design methodology presents an improved targeting to the skeletal muscle and reduced tropism to the liver (9:25 am to 9:42 am) – Ai Vu Hong In addition, Dr. Hong, a member of Genethon’s Progressive Muscular Dystrophies Team, received two ASGCT awards: one for Excellence in Research, which recognizes the top 10 – 15 posters submitted by students and fellows; and the other a Meritorious Abstract Travel Award given to associate members based on their high abstract scores. The following are poster presentations by Genethon scientists (all times are US PDT): Wednesday, May 17, 12 pm – 2 pm Extreme Inter-Individual Variability of Subretinal AAV-Induced Immune Response Even in a Highly Standardized Context [Board No. 721] – Duohao Ren and Sylvain Fisson Assessment of Therapeutical Potential and Advantage of a Dual AAV Approach for Duchenne Muscular Dystrophy [Board No. 663] – Sonia Albini In Vivo Gene Therapy for Lysosomal Acid Lipase Deficiency [Board No. 643] - Marine Laurent Characterization and Quantification of CRISPR/Cas9-Induced Genomic Alterations and AAV Targeted Integration in Human HSPC [Board No. 527] Alexandra Tachtsidi Thursday, May 18, 12 pm – 2 pm Evaluation of Gene Transfer Efficiency in a Mild Model of Dystrophic Muscle Disorder Performed by Machine Learning and Linear Discriminant Analysis [Board No. 1214] – Anthony Brureau Cardiomyocyte Death after AAV Gene Transfer Can Be Related to Proteotoxicity or to Transgene Abnormal Function or Localization [Board No. 884] – Isabelle Richard Predictive Potential of Single Deleterious Variations to Infer on AAV2 and AAV2-13 Capsids Viability [Board No. 874] – Tiziana La Bella Friday, May 19, 12 pm – 2 pm Autophagy Induction Improves Dual AAV Vector Efficacy in a Mouse Model of Glycogen Storage Disease Type III [Board No. 1396] – Louisa Jauze Preliminary Results from a Prospective, Multicentric, Follow Up Standardized Cohort to Assess Natural History of Duchenne Muscular Dystrophy [Board No. 1603] – Fei Cao About Genethon A pioneer in the discovery and development of gene therapies for rare diseases, Genethon is a unique non-profit organization created by a patient association, the AFM-Telethon. A first gene therapy drug, to which Genethon contributed, has obtained marketing for spinal muscular atrophy. With 200+ scientists and professionals, Genethon is pursuing its mission to bring life-changing therapies to patients suffering from rare genetic diseases. 13 products resulting from Genethon’s research are in clinical trials for eye, liver, blood, immune system and muscle diseases. A further6 products are in the preparation phase for clinical trials over the next five years. Find out more: genethon.com Contact: Charles Craig Opus Biotech Communications 404-245-0591 charles.s.craig@gmail.com