EXG-110

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to EXG110, an experimental gene therapy for Fabry disease that’s being developed by Exegenesis Bio and is currently in clinical testing.“The FDA’s decision to grant orphan drug designation to EXG110 highlights the need for better approaches to treat Fabry disease, a debilitating condition that affects thousands of people worldwide,” Zhenhua Wu, PhD, Exegenesis’ CEO, said in a company press release.The FDA’s orphan drug status gives economic incentives to companies that are investing in the development of new treatments for rare diseases — specifically conditions that affect fewer than 200,000 people in the U.S. — which by definition have a small market size that can make it difficult to recoup investment and turn a profit. Most notably, treatments given this designation are guaranteed seven years of market exclusivity if they are ultimately approved by the FDA.“We believe this is validation of our rigorous science, our innovation culture and our strong commitment to rare disease patients,” Wu said. “This is another milestone in our journey to become a truly global gene therapy company.”Fabry disease is caused by mutations in the GLA gene, which provides instructions to make an enzyme called alpha-galactosidase A (alpha-Gal A). This enzyme is normally needed to break down certain fatty molecules. In Fabry disease, lack of functional alpha-Gal A enzyme results in an abnormal buildup of fatty molecules in cells, ultimately causing damage to organs that drives disease symptoms.EXG110 is a one-time gene therapy designed to deliver a working copy of the GLA gene to cells in the liver and heart, allowing production of functional alpha-Gal A enzyme to clear out toxic fatty molecule buildups. The heart is often directly affected by Fabry disease, while the liver is well-suited to serve as a manufacturing hub to produce the enzyme and ship it to other organs in the body.To deliver its genetic payload, EXG110 uses a modified version of a virus, called adeno-associated virus (AAV), that’s been engineered to deliver the therapeutic gene instead of causing a problematic infection. AAV is commonly used as a vector for gene therapies because it’s easy to manipulate in a laboratory and the virus itself doesn’t usually cause disease in people.Exegenesis is currently running a clinical trial testing EXG110 in Fabry disease patients in China. That study has already dosed its first participant. The company said it is also planning to start a trial of EXG110 in the U.S., but didn’t provide further details on the expected start date.In addition to Fabry disease, Exegenesis is also developing gene therapies for other diseases including the eye condition wet age-related macular degeneration and the neuromuscular disorder spinal muscular atrophy.“I would like to congratulate our global team for accelerating progress on all of our pipeline programs and platform technologies. … Our team is operating with a sense of urgency to bring these much-needed treatments to patients worldwide,” Wu said.

PHILADELPHIA--( BUSINESS WIRE )--Exegenesis Bio, a clinical stage global gene therapy company is pleased to announce that US FDA has granted Orphan Drug Designation (“ODD”) to EXG110, a novel gene therapy for Fabry disease, a rare lysosomal disorder that results in excessive deposition of lipids in tissues, eventually leading to renal failure, cardiac disease and strokes. EXG110 is a one-time treatment that delivers the genetic payload directly to liver and heart cells with improved efficacy, safety and dosing. The first patient has been dosed in a China clinical trial and the company plans to initiate a US clinical trial. The FDA’s Office of Orphan Drug Products grants orphan drug designation to support the development of medicines for rare disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation qualifies a company for incentives, including tax credits for qualified clinical trials, exemptions from user fees, and the potential for seven years of market exclusivity after approval. “The FDA’s decision to grant orphan drug designation to EXG110 highlights the need for better approaches to treat Fabry disease, a debilitating condition that affects thousands of people worldwide. We believe this is validation of our rigorous science, our innovation culture and our strong commitment to rare disease patients,” stated Dr. Zhenhua Wu, CEO of Exegenesis Bio. “This is another milestone in our journey to become a truly Global Gene Therapy company. We recently shared updates on our other clinical programs and technology platforms at the European Society for Gene and Cell Therapy meeting, including updates on EXG102/202, a clinical stage gene therapy for wet Age-Related Macular Degeneration (wAMD) and EMC023, a muscle-specific capsid that enables targeted delivery of gene therapies for muscle diseases.” EXG102 is an investigational gene therapy for wAMD that is administered by subretinal injection. Exegenesis Bio is developing a next generation version, EXG202, that incorporates the same genetic cargo, but is delivered to deep retinal cells by a highly-specific ocular capsid that enables administration by intravitreal injection, a less invasive, non-surgical approach. EXG202 has demonstrated a 3 to 5-fold increase in retinal transduction efficiency over currently known ocular-specific capsids in a non-human primate study. “Our unique approach to wAMD is built on three pillars: (1) targeting multiple pathways involved in neovascular disease, including VEGF subtypes A, B, C, D and Angiopoietin 2; (2) packaging our cargo in a proprietary capsid that targets photoreceptors and retinal pigment epithelium more efficiently, and (3) administering the treatment by intravitreal injection, a safe, non-surgical procedure,” emphasizes Dr. Wu. “We believe this will result in a "Best-In-Class" treatment for wAMD and other ocular diseases. We are currently conducting clinical trials in USA and China and hope to share further data in the coming months.” EMC023 is Exegenesis Bio’s proprietary muscle-specific capsid that targets and transduces skeletal muscle tissues more effectively than current benchmark AAV muscle-specific capsids. EMC023 has demonstrated increased skeletal muscle transduction in a non-human primate study – up to 3-fold increase in vector genome copies and up 13-fold increase in transgene mRNA levels. “We believe that we have discovered one of the most specific skeletal muscle targeting capsids known to date,” states Dr. Wu. We are excited to explore the potential of this novel delivery platform in a variety of muscle diseases, including Duchenne Muscular Dystrophy.” “I would like to congratulate our global team for accelerating progress on all of our pipeline programs and platform technologies. We have built a company with full in-house R&D, CMC, Quality and Regulatory capabilities, and we now have three clinical stage programs in USA and/or China: (i) wet Age Related Macular Degeneration, (ii) Spinal Muscular Atrophy, and (iii) Fabry Disease. Our team is operating with a sense of urgency to bring these much-needed treatments to patients worldwide,” emphasizes Dr. Wu. Exegenesis Bio plans to provide further R&D updates on Fabry Disease, wAMD, Spinal Muscular Atrophy and Muscle Tropic Capsid programs during JP Morgan week in San Francisco, Jan 13-16, 2025. About Fabry Disease Fabry disease is a rare X-linked lysosomal disorder that results in excessive deposition of lipids in the tissues. Researchers have identified hundreds of mutations causing Fabry disease in the gene for alpha-Gal A, located on the X chromosome. Deficiency of alpha-Gal A is the main cause for the lysosomal buildup of glycosphingolipids. Progressive glycolipid accumulation can lead to renal failure, cardiac disease and strokes. About wet Age Related Macular Degeneration (wAMD) Nearly 20 million people in the US are living with Age-Related Macular Degeneration (AMD), a progressive eye disease caused by damage to the macula/retina that can lead to blurred vision and blindness. Almost 2 million people have a more severe form of the disease, “wet” AMD (wAMD), which is caused by abnormal blood vessel growth and blood or fluid leakage into the macula, leading to scarring and rapid loss of central vision. wAMD accounts for approximately 90 percent of all AMD-related blindness worldwide. About Duchenne Muscular Dystrophy (DMD) Duchenne muscular dystrophy is a genetic disorder characterized by the progressive loss of muscle. It is a multi-systemic condition, affecting many parts of the body, resulting in deterioration of the skeletal, heart, and lung muscles. Over a million people are living with DMD and other muscle dystrophies worldwide. About EXG110 Gene Therapy for Fabry Disease EXG110 is a one-time treatment for Fabry disease in children and adults, engineered with a proprietary capsid to increase delivery to target heart and liver cells, potentially improving efficacy and safety, and enabling lower dosing. The first patient has been dosed in China and a US clinical trial is planned in 2025. About EXG102-031 Subretinal Injection for wet Age Related Macular Degeneration EXG102-031 is a rAAV-based gene therapy expressing a therapeutic fusion protein that is able to bind/neutralize all known subtypes of Vascular Endothelial Growth Factor (VEGF A, B, C, D) and Angiopoietin-2, which are known to stimulate abnormal blood vessel formation and vascular leakage in the retina. The US and China based clinical trials will evaluate safety and tolerability, as well as visual acuity and central retinal thickness in patients with wAMD. About EXG202 Intravitreal Injection for wet Age Related Macular Degeneration EXG202 is a next generation gene therapy that incorporates the same genetic cargo as EXG102-031 – and is delivered to deep retinal cells by a highly-specific ocular capsid that enables administration by intravitreal injection, a less invasive, non-surgical approach. EXG202 has demonstrated a 3 to 5-fold increase in retinal transduction efficiency over currently known ocular-specific capsids in a non-human primate study About Exegenesis Bio Exegenesis Bio is a clinical stage global gene therapy company with operations in Philadelphia, Boston, Singapore and China. The company’s innovative gene therapy pipeline is based on proprietary capsids, promoters and unique protein engineering designs. Three programs have advanced to the clinical stage: (1) wAMD in USA and China, (2) Spinal Muscular Atrophy (SMA) in China and (3) Fabry disease in China. Exegenesis Bio has built state-of-the-art cGMP manufacturing facilities that include 500L and 2,000L disposable bioreactors for viral vectors and 30L disposable fermenters for plasmids. The company employs over 200 scientific and operations staff worldwide. Please contact us to discuss US and Global collaboration opportunities. Company Website: www.ExegenesisBio.com