ASO for Potential Treatment of AS – GeneTx Biotherapeutics

Quick Overview

GeneTx Biotherapeutics is developing an antisense oligonucleotide (ASO) called GTX-102 for the potential treatment of Angelman Syndrome (AS). AS is a rare genetic disorder caused by the loss of function of the UBE3A gene in the central nervous system. GTX-102 is designed to unsilence the UBE3A gene from the father and has shown promising results in preclinical studies. The company plans to conduct a Phase 1/2 clinical trial to evaluate the safety and efficacy of GTX-102 in AS patients. The trial will involve repeat dosing of the drug via intrathecal administration and will assess various functional domains such as communication, seizures, sleep, cognition, and behavior. The company aims to enroll the first patients in the first half of next year.


In this talk, we are excited to introduce Dr. Scott Stromatt, the CMO of Genetics Biotherapeutics, and Ms. Jennifer Panagoulias, the Vice President of Regulatory Affairs at Genetics Biotherapeutics. Dr. Stromatt has extensive experience in the biopharmaceutical industry, particularly in rare diseases, while Ms. Panagoulias has a long history in rare disease and antisense oligonucleotides. We will also discuss the partnership between Ultragenyx and Genetics Biotherapeutics.

Partnership between Ultragenyx and Genetics Biotherapeutics

Ultragenyx and Genetics Biotherapeutics have formed a partnership to develop a potential treatment for Angelman Syndrome (AS). Ultragenyx was interested in Genetics Biotherapeutics due to their expertise in rare diseases and their approach to drug development. The partnership aims to support the clinical development and regulatory plans for the potential treatment.

Clinical Program for ASO Treatment

The potential treatment for AS is an investigational antisense oligonucleotide (ASO) called GTX-102. ASOs are single-strand DNA-RNA molecules that target RNA to alter protein expression. GTX-102 is designed to silence or unsilence the UBE3A gene from the father, which is related to the loss of function of the UBE3A protein in the central nervous system.

Preclinical studies have shown promising results, including a reduction in symptoms in a mouse model of AS and increased UBE3A protein expression in the brains of monkeys. The clinical program for GTX-102 is a Phase 1/2 trial, which will focus on safety, pharmacokinetics, and clinical activity. The trial will involve repeat dosing of GTX-102 through intrathecal administration (lumbar puncture).

Caregiver Input in Study Design

The study design for the clinical program has been informed by input from caregivers of AS patients. A caregiver advisory board provided feedback on the protocol, visit schedule, and procedures involved in the study. The feedback highlighted the importance of clear communication, minimizing procedures (especially blood draws), providing comfort items during clinic visits, and considering the specific needs of each family.

Study Objectives and Measures

The primary objective of the clinical trial is to assess the safety of GTX-102. Secondary objectives include evaluating pharmacokinetics and exploring the drug’s impact on various functional domains, such as communication, seizures, sleep, cognition, adaptive behaviors, and global clinical assessment. Multiple measures and tools will be used to assess these domains, including psychometric tests, seizure diaries, EEGs, sleep diaries, and wearable devices.

Trial Status and Future Plans

The clinical trial is currently in the site identification and qualification phase. The first patients are expected to be enrolled in the first half of the next year. The trial will be open-label, meaning all participants will receive GTX-102. The study will provide valuable safety and efficacy data, which will inform future studies and potential approval.


The potential treatment for AS using GTX-102 shows promise in preclinical studies and is now entering a Phase 1/2 clinical trial. The partnership between Ultragenyx and Genetics Biotherapeutics aims to support the development and regulatory plans for this treatment. Caregiver input has played a crucial role in shaping the study design, ensuring that the trial is patient-centered and minimizes burden on families. The trial will assess safety, pharmacokinetics, and clinical activity across various functional domains. The ultimate goal is to provide a safe and effective treatment for AS patients.

Talk details

  • Title: ASO for potential treatment of AS – GeneTx Biotherapeutics
  • Author(s): Yael Weiss, Scott Stromatt, Jennifer Panagoulias
  • Author(s)’ affiliation: Ultragenyx Pharmaceutical; GeneTx Biotherapeutics
  • Publication date: 2019-12-27
  • Collection: 2019 FAST Science Summit