Many disease‑causing genes are too large to be packaged into standard AAV gene therapy vectors, leaving a long list of otherwise gene-therapy-ready conditions without viable treatments. SpliceBio is leveraging a protein splicing platform based on engineered split inteins to overcome the cargo limitations of AAV gene therapy vectors, enabling delivery of large genes to potentially treat a broad range of monogenic conditions. The company’s lead program is a dual AAV gene replacement therapy to treat Stargardt disease, a rare inherited condition that causes progressive vision loss. Miquel Vila-Perello, CEO of SpliceBio, discusses the company’s platform technology that enable to the delivery of large genes in AAV vectors, its work to date in Stargardt disease, and preclinical data across more than 20 large-gene targets supporting its platforms use in ophthalmology and CNS indications.

Fitting Big Genes into Small Vectors

RARECast

# Full Transcript

**Podcast:** RARECast

## Participants

- **Daniel Levine** (Levine Media Group)
- **Michael Villepelion** (SpliceBio)

## Transcript

The following RARECast podcast is made possible through support from the Global Genes Corporate Alliance. The members of the Corporate Alliance support Global Genes' mission and programs, work to meet the vital needs of people with rare diseases, and address inequities they face. To learn more about the Corporate Alliance or how your organization can become a member, join us at globalgenes.org and choose Corporate Alliance under the About tab.

I'm Daniel Levine and this is RARECast. Many disease-causing genes are too large to be packaged into standard AAV gene therapy vectors,

leaving a long list of otherwise gene therapy-ready conditions without viable treatments. Spice Bio is leveraging a protein-spicing platform based on engineered split intines to overcome the cargo limitations of AAV gene therapy vectors, enabling delivery of large genes to potentially treat a broad range of monogenic conditions.

The company's lead program is a dual AAV gene replacement therapy to treat Stargardt disease, a rare inherited condition that causes progressive vision loss. Michael Villepelion, CEO of Spice Bio, discusses the company's platform technology that enables the delivery of large genes in AAV vectors, its work-to-date in Stargardt disease, and preclinical

data across more than 20 large gene targets supporting its platform's use in ophthalmology and CNS indications. Michael Villepelion, CEO of Spice Bio, and its platform technology that enables the delivery

of genes that are too large for conventional AAV vectors. Let's start with the problem you're seeking to address with your platform technology. How limiting is the cargo size of AAV vectors, and what are the practical consequences of those constraints? So, as you know, for gene therapy, the key idea is to be able to deliver a gene that treats the underlying cause of the disease.

So, for many monogenic rare diseases, those diseases are caused by mutations on specific genes. And so, an efficient way to try to treat those diseases is by delivering a correct copy of that gene. And we have several examples of those approaches, one of them being Lux-Turna, approved for lever congenital amaurosis, another form of a rare retinal disease.

And all those approaches rely on the use of vectors to be able to deliver that gene into the target cells. In the case of Stargard disease, those are photoreceptor cells in the back of the eye, in the retina. So, the cargo, sorry, the vehicles that we typically use in gene therapy to be able to deliver those genes are AAVs, which stands for adeno-associated viruses. And these are great vectors for gene delivery.

We know they can deliver those genes very efficiently, but they have a limited cargo capacity, as you were saying. That basically means that you can only put genes of a certain size. So, to treat diseases that...

Fitting Big Genes into Small Vectors

Transcript

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Fitting Big Genes into Small Vectors

Transcript

Built for investment professionals

Every day you wait, your competitors are findingedge in conversations you're not hearing.

Every day you wait, your competitors are finding
edge in conversations you're not hearing.