FDA grants Orphan Drug Designation to first-in-class gene therapy for STXBP1 disorder

The US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Capsida Biotherapeutics for CAP-002, a novel, first-in-class gene therapy for STXBP1 disorder, developed in collaboration with Dr. Mingshan Xue at Texas Children’s Duncan Neurological Research Institute (Texas Children’s Duncan NRI). STXBP1 disorder, which affects up to one in 26,000 children globally, is a devastating developmental and epileptic encephalopathy that causes intellectual disability, motor issues, and treatment-resistant epilepsies that can lead to sudden unexpected death in epilepsy.

Dr. Mingshan Xue, associate professor at Baylor College of Medicine and Caroline DeLuca Endowed Scholar at the Texas Children’s Duncan NRI and Cain Laboratories, began building a research program dedicated to STXBP1 disorder in 2014 after he first met Elizabeth and Anthony DeLuca and their beloved daughter, Caroline, who was suffering from the disorder. As a neuroscientist focused on brain circuit function, Dr. Xue had not previously worked on any epilepsy or neurodevelopmental disorder but was inspired by the DeLuca family to solve this devastating disorder affecting Caroline.

“With the support of the DeLuca family, I was able to build and train a highly skilled research team to pioneer a promising new gene therapy program for STXBP1 disorder, which results from mutations in the STXBP1 gene and is among the most common causes of pediatric epilepsies,” said Dr. Xue. “I am so grateful for Elizabeth and Anthony and their commitment to our mission as we strive to find answers for our patients and their families. In every part of our work, Caroline continues to be an inspiration to us.”

As part of his research program, Dr. Xue developed a proprietary mouse model that replicates STXBP1 disorder and demonstrated proof-of-concept that a gene therapy approach could reverse the disorder. To achieve the level of widespread protein restoration needed in humans, Dr. Xue entered into a collaboration with Capsida Biotherapeutics. Capsida’s proprietary, adeno-associated virus (AAV) engineering platform allowed them to identify an engineered capsid that could achieve widespread expression of STXBP1 protein in the brain of primates. Simultaneously, the capsid has much reduced effects on off-target organs, such as the liver, following intravenous (IV) delivery. 

In the first half of 2024, the laboratory of Dr. Xue, in collaboration with Capsida, had a major breakthrough. In innovative preclinical studies, they identified the minimal amount of STXBP1 genetic material needed to alleviate symptoms in animal models with STXBP1 disorder, with long-lasting effects, and also identified doses that achieved higher levels of STXBP1 and greater symptom correction. The discovery marked an exciting turning point in their search for a new effective therapy.

“When our daughter, Caroline, was first diagnosed with STXBP1 disorder, we began working with leading expert Dr. Mingshan Xue at the Texas Children's Duncan NRI whose research has transformed our understanding of this disorder,” said Elizabeth DeLuca. “Now, this promising new gene therapy is a huge milestone that brings us ever closer to a successful treatment. We are so grateful to Dr. Xue and his team for their dedication and commitment to creating a better future for our precious children suffering from this devastating disease.” 

The FDA’s ODD is awarded to encourage the development of innovative new therapies for devastating rare diseases. Capsida is advancing the program with the expectation of filing an Investigational New Drug application with the FDA in the first half of 2025, which, if accepted, would then launch clinical trials for the therapy. 

“This new gene therapy is a truly outstanding achievement and is a beautiful example of our mission at the Duncan NRI,” said Dr. Huda Zoghbi, founding director of the Texas Children’s Duncan NRI, distinguished service professor at Baylor College of Medicine, and investigator at the Howard Hughes Medical Institute. “Dr. Xue’s discoveries have charted new paths forward for therapeutic development for STXBP1 disorder, and in the coming years we hope this will help change outcomes for the children and adults affected by this disorder. Caroline DeLuca, who sadly passed away from this disease, inspired Dr. Xue and others at the Duncan NRI to push as hard as we can to develop treatments for devastating neurological disorders.”  

Read more about Capsida Biotherapeutics here. 

About Texas Children’s Hospital

Texas Children’s, a nonprofit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children’s hospital in Texas and among the top in the nation, Texas Children’s has garnered widespread recognition for its expertise and breakthroughs in pediatric and women’s health. The system includes the Texas Children’s Duncan NRI; the Feigin Tower for pediatric research; Texas Children’s Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children’s Hospital West Campus, a community hospital in suburban West Houston; Texas Children’s Hospital The Woodlands, the first hospital devoted to children’s care for communities north of Houston and Texas Children’s Hospital North Austin, the new state-of-the-art facility providing world-class pediatric and maternal care to Austin families. The organization also created Texas Children’s Health Plan, the nation’s first HMO focused on children; Texas Children’s Pediatrics, the largest pediatric primary care network in the country; Texas Children’s Urgent Care clinics that specialize in after-hours care tailored specifically for children; and a global health program that is channeling care to children and women all over the world. Texas Children’s Hospital is affiliated with Baylor College of Medicine. 

About the Texas Children’s Duncan NRI

Founded in 2010 at Texas Children’s Hospital, the Duncan NRI researches and discovers treatments for devastating brain disorders that impact more than a billion people worldwide, including 300 million children. As the largest children’s hospital in America, Texas Children’s Hospital is uniquely positioned to study brain development in children to understand how the brain changes later in life. The Texas Children’s Duncan NRI spans 344,000 square feet and covers 13 floors. It is home to more than 400 multidisciplinary researchers who collaborate with physicians for rapid lab-to-bedside discovery, facilitating innovation that would be impossible in traditional scientific silos. This approach has led to 1,700 published discoveries, the identification of 90 novel disease-causing genes, and major breakthroughs in autism, epilepsy, Alzheimer’s disease, depression, obsessive compulsive disorder, and other neurological and psychiatric disorders. Texas Children’s Hospital covers all of the Duncan NRI’s annual operating costs, so every dollar donated directly supports research. 

About Capsida Biotherapeutics

Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida’s proprietary engineered capsids enable high levels of neuron transduction while limiting tropism to non-target organs, such as the liver. Capsida’s wholly owned pipeline includes a potential first-in-class treatment for STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE), which received FDA Orphan Drug Designation (ODD), best-in-class treatment for Parkinson’s disease associated with GBA mutations (PD-GBA), and best-in-class therapy for Friedreich’s ataxia. The STXBP1-DEE and PD-GBA programs are on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating partnerships with AbbVie, Lilly, and CRISPR Therapeutics. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech.