Evaluating Epigenetic Gene Therapy for the Treatment of FSHD
Alexandra Collin de l’Hortet, PhD, the head of therapeutics at Epic Bio, discussed EPI-321, an investigational treatment for facioscapulohumeral muscular dystrophy.
Alexandra Collin de l’Hortet, PhD
Epic Bio is currently developing EPI-321, an investigational epigenetic gene therapy product intended to treat facioscapulohumeral muscular dystrophy (FSHD). The company recently presented preclinical results regarding the therapy at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.
At the conference, CGTLive® interviewed Alexandra Collin de l’Hortet, PhD, the head of therapeutics at Epic Bio, about EPI-321, which uses a CRISPR-based system delivered by an adeno-associated virus (AAV) vector. She explained the concept behind the therapy, and also discussed challenges encountered thus far during development and future plans for further research for the company.
CGTLive: Can you give some background about Epic Bio?
Alexandra Collin de l’Hortet, PhD: At Epic bio, we are developing a gene therapy product for FSHD. FSHD is a muscular disease affecting most of the skeletal muscle in the body, and we have developed a product that can really treat FSHD by going after the root cause of the disease, which is epigenetic by nature. We had presented last year at the ASG CT, kind of like the first pre clinical proof of concept data, and we are following up this year by showing a more complete non clinical program as we prepare to enter into the clinic this year.
What did Epic Bio present at ASGCT this year?
This year, we've presented data in various nonclinical models. We have shown data directly on patient cell lines in vitro, we have shown efficacy data in a very robust and translational model, and we have also shown muscle rescue data in an ex vivo model, as well. So we've used a variety of nonclinical models to demonstrate the efficacy of our product, called EPI-321.
How would you summarize the key takeaways for doctors and the broader healthcare community?
Essentially, the key takeaway for the product is that we have a CRISPR technology at Epic and for this product we deliver via an AAV that targets specifically the skeletal muscle. The uniqueness of our product is that it acts by adding a methylation mark, which is really the root cause of the disease in FSHD, it's a loss of methylation issue. The key takeaway is that we can rescue methylation on that particular locus in the genome and that correlates very well and that translates very well into a suppression of the toxic gene target that is the cause of that disease—a complete reduction of cell death or apoptosis and eventually a rescue of muscle function. Those are the key takeaways from the product that starts with the root cause, the methylation, and all of the positive effect that restoring methylation has on that disease.
Are there ongoing challenges or any specific areas of interest for future research for this approach that you can discuss?
I think the challenge for this disease is that there hasn't been as many products developed as there are for other diseases so the tools available are not as as present as they are for other diseases. We have to be creative in our nonclinical package, and that's why we have decided to really explore various models. Another challenge for this disease is that the molecular background is heterogeneous and the clinical manifestation is heterogeneous. So to really try to address that challenge, we've tested our product in a variety of patient cell lines with a variety of genetic and clinical background to demonstrate that our product works across the board, irrespective of the heterogeneity that comes with this disease.
Is there anything we didn't cover with the previous questions that you just want to share?
We've done a lot of work and research to establish a potential threshold for success, and that's how we've really looked at our nonclinical data. Now we are very excited and we expect it to translate into clinical data. That's definitely something to look forward to with this program.
We also have another program with Epic Bio that I think speaks to the nature of the platform and [shows] that we can really address any type of disease. I would also mention that we're looking forward to discussing with companies that have specific gene targets in mind because we have the technology to really go after it, and so we can help patients together.
This transcript has been edited for clarity.
Click here to view more coverage of the 2024 ASGCT Annual Meeting.
