Roche Angelman Syndrome Program Update

Quick Overview

Roche provided an update on their Angelman Syndrome Program at the 2020 FAST Science Summit. They discussed the history and progress of the program, including the FREESIAS observational study and the UBE3A-LNA molecule. They also introduced TANGELO, their Phase 1 drug study. Roche emphasized their commitment to rare diseases and their focus on developing a potentially disease-modifying treatment for Angelman syndrome. They discussed the mechanism of action of their lead compound, which targets the UBE3A antisense to activate the paternal allele and increase UBE3A protein production. The FREESIAS study is fully enrolled, and they are collecting data to inform future trial designs. They also provided details on TANGELO, an open-label study investigating the safety and efficacy of UBE3A-LNA in participants with Angelman syndrome. Roche explained the importance of clinical trials in testing new drugs and ensuring patient safety. They also discussed the use of lumbar puncture for intrathecal administration of the drug. Overall, Roche expressed their gratitude to the Angelman syndrome community and their commitment to developing meaningful treatments for the disorder.

Introduction

Good morning, good afternoon, good evening, everyone. It’s a pleasure to be here today and to be part of the FAST Virtual Family Science Summit. My name is Brenda Vincenzi. I am the medical director for the Angelman Syndrome Program at Roche, based in Basel, Switzerland.

Roche and Genentech

Roche and Genentech are one company with a mission to transform the lives of people with serious diseases and their families. We have a long-standing commitment in rare diseases and have been in the Angelman Syndrome space for the past five years in partnership with many organizations and researchers. We have developed 38 FDA approved medicines and have 22 FDA breakthrough designations.

History and Progress

In 2015, we started our journey in the Angelman Syndrome space by listening and learning from the Angelman syndrome community. In collaboration with ABOM (Angelman Biomarker Outcomes Alliance), we developed the disease concept model in Angelman syndrome, which was recently published in the Child Psychiatry and Human Development Journal. In 2018 and 2019, we started the co-creation of FREESIAS with families and the scientific community. We also began preparing for TANGELO, our Phase 1 drug study. The first participant in TANGELO was enrolled in August 2020, and recruitment for FREESIAS was completed in September 2020.

Lead Compound: UBE3A-LNA

We have identified a lead compound, UBE3A-LNA, that has shown promising results in the lab. This compound targets the UBE3A antisense, a long RNA that silences the paternal allele of the UBE3A gene. By removing this silencing effect, we aim to activate the paternal allele and increase the production of UBE3A protein.

FREESIAS Observational Study

FREESIAS is an observational endpoint enabling study in Angelman syndrome. The primary objectives of this study are to assess the feasibility and value of novel endpoints and biomarkers to inform clinical trial design. The study has enrolled 40 individuals with Angelman syndrome aged 1 to 12, 10 individuals with Angelman syndrome aged 18 and above, and 20 controls for comparison. Recruitment for FREESIAS was completed in September 2020.

TANGELO Phase 1 Drug Study

TANGELO is our Phase 1 drug study for Angelman syndrome. It is an open-label study, meaning that all participants with Angelman syndrome will receive the drug. The study aims to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of UBE3A-LNA. We plan to enroll up to 66 participants with Angelman syndrome aged 1 to 12. The study is being conducted at multiple centers in the US, Canada, and Europe.

Clinical Trials and Lumbar Puncture

Clinical trials are medical research studies that involve people. They are conducted to test the safety and efficacy of new drugs. In the case of Angelman syndrome, lumbar puncture is used to administer the drug directly into the cerebral spinal fluid (CSF) surrounding the brain and spinal cord. This allows the drug to bypass the blood-brain barrier and reach the target area more effectively.

Conclusion

We are excited about the progress we have made in the Angelman Syndrome Program at Roche. Our lead compound, UBE3A-LNA, shows promise as a potentially disease-modifying treatment for Angelman syndrome. We are currently conducting the FREESIAS observational study and the TANGELO Phase 1 drug study to gather more data and assess the safety and efficacy of the treatment. We are grateful to all the families, trial site teams, and collaborators who have contributed to our research. Thank you for your attention.