AAV Gene Therapy – PTC Therapeutics

Quick Overview

During the 2019 FAST Science Summit, Dr. Ed Weeber and Stephanie Ciarlone from PTC Therapeutics discussed their gene therapy program for Angelman Syndrome. PTC Therapeutics is a rare disorder company with a focus on RNA-based therapies and small molecules. They have a gene therapy pipeline that includes AADC deficiency, Friedreich’s ataxia, and Angelman Syndrome. PTC is committed to developing a gene therapy platform that is differentiated and scalable, with a focus on targeted dosing and multidisciplinary care for patients. They have conducted preclinical studies using AAV gene therapy in mouse and rat models, and are working towards conducting a first-in-human clinical trial. PTC is also establishing internal manufacturing processes to provide the best products for clinical trials and human use. They encourage families to participate in the global Angelman registry to help inform successful clinical trials.

Introduction

In this talk, we will be discussing the AAV gene therapy program of PTC Therapeutics. We are joined by Dr. Ed Weeber, Vice President of Neuroscience at PTC Therapeutics, and Stephanie Ciarlone, a PhD working in the Drug Development Division at PTC Therapeutics.

PTC Therapeutics

PTC Therapeutics is a science-led rare disorder company with a focus on RNA-based therapies and small molecules. They have a broad gene therapy pipeline and are committed to being a fully integrated, innovative rare disorder company with multiple platforms and a global footprint.

AAV Gene Therapy Platform

PTC Therapeutics is focused on developing a differentiated and scalable AAV gene therapy platform. They are initially targeting monogenic disorders that can be treated throughout a patient’s lifetime, allowing for a larger treatment window. They are also focused on targeted dosing, delivering the vector to specific cells of interest in the central nervous system (CNS), which could potentially lead to lower dosing. PTC Therapeutics aims to cultivate centers of excellence to provide multidisciplinary care for each patient.

Pipeline and Angelman Syndrome Program

PTC Therapeutics has a broad gene therapy pipeline with a focus on rare CNS diseases. Their AADC deficiency program is on track to have a BLA filed by the end of the year, and their Friedreich’s ataxia program is planned to be in the clinic mid-2020. Angelman syndrome is their third publicly announced indication, and they are fully committed to this program. They also have cognitive disorders in the pipeline that have not yet been publicly announced.

History of the Angelman Syndrome Program

Dr. Ed Weeber discusses the history of the Angelman syndrome program. They conducted experiments using AAV to deliver the UBE3A gene to the hippocampus of AS mouse models. The results showed expression of the UBE3A protein in the neurons and a recovery of symptoms related to synaptic plasticity, learning, and memory. They also conducted experiments in non-genetically altered rats to study the safety and efficacy of overexpressing UBE3A.

Status Update and Future Plans

PTC Therapeutics is currently contracting out manufacturing and has a collaboration with Aldebaran to support this. They have also acquired a biologics facility in New Jersey and plan to transition it into an in-house facility. They are establishing internal manufacturing processes to provide the best products for clinical trials and human use. They encourage families to participate in the global Angelman registry and keep their information up-to-date to support successful clinical trials.

Conclusion

PTC Therapeutics is dedicated to developing AAV gene therapies for rare CNS diseases, including Angelman syndrome. They are committed to safety and efficacy in their research and are working towards conducting a first-in-human clinical trial. They encourage families to participate in the global Angelman registry and stay informed about the progress of their research.