Expert Discusses Investigational AVB-101 for Frontotemporal Dementia

Lisa Deschamps, CEO of AviadoBio, discusses frontotemporal dementia (FTD) and AVB-101, a one-time therapy designed to stop disease progression by delivering a functional copy of the GRN gene and restoring progranulin levels in the brain. According to the company, FTD is a form of early onset dementia that causes changes in personality changes, behavioral disturbance, and loss of language. It effects executive function, behavior and language.

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Q:Can you give a brief overview of the ASPIRE-FTD clinical study?

Lisa Deschamps: ASPIRE is a study designed to assess investigational therapy AVB-101, which is designed to assess safety, [the] coprimary endpoint of safety and efficacy, in patients who have a mutation in their GRN gene. The GRN gene is what helps your body produce progranulin, and this is a gene supplement program, which means that, if the therapy goes successfully, as we hope, it will be able to provide a working functional copy of this gene for patients who have this mutation.

Q: What have the efficacy data shown so far for this drug?

Lisa Deschamps: We just kicked off the ASPIRE trial in the last couple of weeks. To date, we have no clinical data. Obviously, we've from our preclinical data package. We've looked at data across mice, sheep, and [nonhuman primates], and there we saw really nice biodistribution, which we hope will translate to a clinical benefit for patients, and very much a favorable safety profile, which we also hope will translate to a very favorable safety profile for patients. But right now, we're just kicking off the trial where we've got 2 active sites open in a couple of key countries in Europe, and we'll be focusing our efforts on recruiting.

Q:How is AVB -101 administered?

Lisa Deschamps: AVB-101 will be administered as a one-time dose directly into the brain via a minimally invasive surgical procedure performed by a neurosurgeon. As we know a lot about FTD, it starts in the frontal lobe, but as the disease progresses, it becomes more of a global disease in nature. By delivering intrathalamically, we believe we'll be able to not only address where the disease starts, but also follow the disease to all the important cortical regions as the disease progresses.

Q:How does frontotemporal dementia with the GRN gene mutation differ from other forms of dementia?

Lisa Deschamps: As you mentioned, this is a monogenic form. The root cause of it is definitely caused by the genetic mutation in the body. Again, these patients have a mutation in the GRN gene. [The] GRN gene is really what tells the body to produce progranulin levels. By delivering a healthy functioning copy, we can really address the root cause of the disease. In other forms of dementia that are not monogenic or not caused by genetic form, it's very different where you can't directly address the root cause, like you can here.

Q:Why is effective brain distribution of the progranulin protein challenging, and how does this administration technique address that?

Lisa Deschamps: [Central Nervous System (CNS)] disease overall is difficult because our blood brain barrier that we all have is really designed to help protect our body from foreign substances, while allowing nutrients, etc. Any therapeutic is difficult for CNS disease, because ideally, you want to be able to get into the brain and/or the spinal cord, depending on the particular CNS disorder. Our focus is, as a company overall, is direct delivery approaches, so pairing therapeutics that we know a lot about with a direct delivery approach. By going intraparenchymal, direct into the brain and into the thalamus, were able to bypass in a sense, this challenge that exists in being able to cross the blood brain barrier, because we're delivering direct into the affected areas. We’re able to then use very little dosages as well. Because we're doing this direct delivery approach, we're also very much expecting to see none to very little systemic exposure, which is really also important. When we did our preclinical work, we didn't see anything in the liver, nothing in the serum. So again, trying to find the right balance by being able to deliver the maximum therapeutic benefit for patients while minimizing any safety risks.

Q:Recently, the FDA cleared the investigational new drug application for the drug, as well as fast track designation. What are the next steps for AVB-101?

Lisa Deschamps: Our next step is continuing to recruit patients in Europe and then open up the US market and start recruiting and enrolling patients there as well. It will take us a few months to get sites contracted and then we'll be able to expand our recruiting efforts from Europe into now the US as well.

Q:Is there anything else you would like to add?

Lisa Deschamps: At AviadoBio, we are really on a mission to help transform and to potentially cure CNS diseases. We’re starting this effort in neurodegeneration in important unmet need areas like FTD as well as expanding into [amyotrophic lateral sclerosis.] We have 4 programs in discovery. Everything we do is focused on, not only in the therapeutic, but the delivery so we do see ourselves as a true drug and delivery company. We're very much committed to bringing these potential benefits to patients who are in so much great need.