2023 Ionis Pharmaceuticals Update

Quick Overview

Becky Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals, provided an update on the company’s progress in developing a treatment for Angelman Syndrome. Ionis, in partnership with Biogen, is developing an antisense oligonucleotide (ASO) called ION582. The ASO is designed to unsilence the father’s copy of the UBE3A gene, which is normally silenced in neurons, to produce the UBE3A protein in the brain. The HALOS clinical trial, the first trial in humans, is currently testing the safety and tolerability of ION582. The trial is progressing as planned, with all tested doses well-tolerated and no safety concerns or drug-related adverse events reported. Ionis plans to continue the trial through 2023, extending the age range and testing different mutations based on data from the HALOS trial.


Hello, I’m Becky Crean, Executive Director of Clinical Development at Ionis Pharmaceuticals. I’d like to extend my gratitude to the Angelman Syndrome Foundation for inviting us to provide an update to the community virtually. We’ve been involved with the community for many years now, and it’s truly remarkable to see the advances made year after year towards developing a treatment for individuals living with Angelman Syndrome. Despite some setbacks and disappointments, which are not uncommon in drug development, Ionis, together with our partners at Biogen, remain committed to developing our ASO, ION582.

About Ionis Pharmaceuticals

Founded in 1989, Ionis Pharmaceuticals has a single mission: to turn antisense oligonucleotides, or ASOs, into a therapy. Over the last 30 years, we’ve been dedicated to developing and advancing this technology. We’ve broadened our scope to include additional types of RNA targeting therapies in addition to ASOs. We’ve had some success along the way, bringing four transformational medicines to the market and to the patients who need them.

We have a pipeline full of ASOs in development, many in the clinics, some in the research for the treatment of a variety of neurological diseases like Parkinson’s, Alzheimer’s, ALS, Angelman syndrome. We’ve about doubled in size since I began working here. We now have over 800 employees and still counting. We’re headquartered in Southern California in a town called Carlsbad, with offices in Boston and Dublin.

Our Products

We developed Spinraza to treat spinal muscular atrophy, Tegsedi to treat polyneuropathy, Waylivra to treat FMS, and the most recently approved drug called Qalsody is an ASO designed to treat a very rare genetic form of ALS. We have a long history and a lot of experience in developing genetic medicines, specifically to treat rare diseases caused by genetic abnormalities.

Lessons from Spinraza

We learned a lot from our experience with developing Spinraza that we can and have been applying to developing our treatment for individuals with Angelman syndrome. SMA, like Angelman syndrome, is a rare monogenetic disease, meaning it’s caused by a mutation in one single gene. But the symptoms are not all the same in each person.

We need to really understand and know the disease very well so that we can develop a drug to treat it. That’s why natural history studies are so important. They really do allow us to collect invaluable data to better understand the disease. We also need to make sure we talk with you, the families, so that we can understand what’s important to you for a treatment.

The HALOS Clinical Trial

Ionis has been working on a treatment for Angelman syndrome for about the last 9 or 10 years. Our HALOS clinical trial is the first trial in humans, and its primary focus is on testing the safety and tolerability of the drug.

What is an ASO?

Our ASOs are small strings of nucleotides, and they bind to the RNA, which, in theory, corrects the mistake that it has on it. In turn, it’ll either produce more of the protein our bodies need or less of it, depending on what the issue is. So, ASOs are considered disease modification drugs because it targets the source of the disease.

The Development of ION582

ION582 was identified after extensive screening, first in cells in animals. We started by screening over 3000 ASOs that bind to a particular region on the antisense transcript. And from there, we picked the best ones to test in transgenic mice, which have the human gene inserted into them.

We tested them in Angelman mouse models and also iPSC neurons. And from there, we took the best ones that came out of all those testings, and then tested a group in large animals, non-human primates. And from there, we selected ION582 out of over 3000 ASOs because it was the safest and most effective molecule for taking into humans.

The HALOS Trial

The HALOS trial is a combination of a phase 1 and a phase 2, and each individual will receive several doses of the ASO over a period of about 3 months. And everyone receives drug. There’s no placebo in this first trial.

Progress and Future Plans

We’ve been running HALOS for a little over a year now, and we’re actually right where we should be. And really, thanks to all of you, the families, the sites, and the clinicians for your interest and willingness to be in the trial. We understand that it’s a significant commitment with no guarantee that your child will receive any benefit from being in the trial. But really, because of you, we continue to advance and make progress, and the study is progressing as planned.


We’ve made great progress over the past year, and as I mentioned at the beginning, Ionis and Biogen truly remain committed to developing a treatment for individuals living with Angelman syndrome. It may seem like it’s taken a long time, but we need to make sure we’re thoughtful and thorough at each stage of this process.

We want to make sure that we first and foremost determine if the drug is safe before moving to the next phase. So, to answer that question, we need to first complete the HALOS trial. We need to complete both Parts 1 and 2, so the study will continue to run through the rest of 2023.

I just want to express my sincere appreciation for your time today. All of us at Ionis and Biogen are deeply committed to the work we do on behalf of the Angelman community. And we’ve made great progress and we couldn’t have done it without you. So, we thank you for your commitment to doing this together. Thank you.

Talk details

  • Title: 2023 Ionis Pharmaceuticals Update
  • Author(s): Becky Crean
  • Author(s)’ affiliation: Ionis Pharmaceuticals
  • Publication date: 2023-07-07
  • Collection: 2023 ASF Virtual Conference