Preclinical data from LBIO-115 exon 51 program demonstrate superior levels of exon-skipping that result in high levels of dystrophin restoration

Data presented at the CureDuchenne FUTURES 2023 National Conference

SAN DIEGO, CA, USA I April 20, 2023 I Locanabio, Inc., a genetic medicines company developing RNA-targeted therapeutics for patients with rare genetic neuromuscular and neurodegenerative diseases, today announced the first presentation of data from its next generation engineered small nuclear RNA, or snRNA, platform, which is designed to efficiently deliver targeted snRNA payloads via an adeno-associated virus (AAV) for long-term therapeutic expression.

The presentation titled “Enhanced Exon-skipping with Next Generation Vectorized snRNAs for the Treatment of DMD” will highlight preclinical data from the company’s LBIO-115 program, which is in development for the treatment of DMD patients with mutations amenable to exon 51 skipping. Ranjan Batra, Ph.D., Locanabio’s senior vice president of research and development, will present the data at the Cure Duchenne Futures 2023 National Conference, which is being held April 20-23 in San Diego, CA.

“We are excited to share data from our snRNA platform publicly for the first time and believe that this platform has the potential to unlock the use of snRNAs as a versatile single administration therapeutic modality,” said Jim Burns, Ph.D., Locanabio’s chief executive officer. “Leveraging our deep knowledge of RNA targeting systems and AAV delivery, we have developed our platform to improve the deployment of snRNAs via our proprietary AAV packaging and manufacturing approach.”

Dr. Burns continued, “Our initial application of snRNAs is in enhanced exon-skipping for the treatment of DMD. Mutations in the dystrophin gene and corresponding messenger RNA, or mRNA, lead to little or no functional dystrophin protein being produced, which causes progressive muscle degeneration and weakness. We have designed snRNA-based exon-skipping constructs that can target multiple splicing regulatory sites in the dystrophin mRNA for enhanced exon-skipping and production of a near full-length protein with a one-time administration. Based on these attributes, we believe our technology has the potential to be a best-in class therapeutic option for DMD patients.”

Data presented at the 2023 FUTURES conference demonstrate that in patient-derived muscle cells harboring mutations amenable to exon 51 skipping, treatment with Locanabio’s snRNA construct induced robust exon 51 skipping with >99% exon-skipping in DMD myotubes and 99% in induced pluripotent stem cell (iPSC)-derived cardiomyocytes.

In a model of DMD (hDMD-Δ52 transgenic mdx mice), LBIO-115 treatment resulted in:

  • Greater than 80% exon 51 skipping in skeletal muscle following intramuscular injection of LBIO-115 with greater than 50% of muscle fibers positive for dystrophin protein after only 4 weeks.
  • Exon 51 skipping levels in heart, diaphragm and skeletal muscle were >95%, >70% and >60% respectively, resulting in greater than 50% of muscle fibers positive for dystrophin protein, only 4 weeks after intravenous administration of LBIO-115, as well as improvements in muscle pathology and reductions in serum creatine kinase, a marker of muscle damage.

“Based on the strength of these data, we have advanced LBIO-115 into investigational new drug-enabling studies. The vectorized snRNA platform enables rapid expansion to other patient populations and we currently have programs in lead optimization for mutations amenable to exon 53, 45 and 44 skipping,” said John Leonard, Ph.D., Locanabio’s chief scientific officer. “The therapeutic potential of the platform goes well beyond exon skipping for DMD and we are leveraging the efficient delivery and precise multi-targeting ability of vectorized snRNAs to develop novel therapeutics across a broad range of rare genetic diseases.”

Locanabio’s exon-skipping approach for DMD uses its vectorized snRNA platform in which an AAV vector is used to deliver engineered snRNAs that target multiple splicing regulatory sites in the dystrophin mRNA to promote efficient exon skipping and production of a minimally truncated but functional dystrophin protein. Exon-skipping therapies have the potential to offer clinical benefit for the approximately 80% of DMD patients whose disease is caused by dystrophin mutations that are amenable to exon skipping. Locanabio expects to present additional data at an upcoming peer-reviewed scientific conference.

Locanabio’s Vectorized snRNA Platform
Locanabio is using engineered small nuclear RNAs, or snRNAs, delivered using AAV gene therapy to modify disease-causing messenger RNA with a one-time administration. snRNAs target RNA exclusively and precisely and are non-immunogenic. They can effect a wide variety of mechanisms including exon-skipping mediated reading frame restoration, mRNA knockdown, increase in protein levels as well as toxic repeat-blocking and RNA editing. Their small size allows the delivery of multiple snRNAs in a single AAV vector which can be used to increase potency or effect several different RNA modifications.

About Duchenne Muscular Dystrophy (DMD)
DMD is a rare fatal X-linked recessive degenerative neuromuscular disorder caused by mutations in the dystrophin gene. The disease affects approximately 1 in every 3,500 to 5,000 males born worldwide. The dystrophin gene is the largest human gene. DMD causing mutations can occur at various places in the gene and most result in large exon deletions or duplications and dysfunctional dystrophin protein. Dystrophin plays a key structural role in muscle. It is one of a group of proteins whose function is to strengthen muscle fibers and protect them from injury as muscles contract and relax. Without it, muscle cells become damaged which leads to muscle wasting. Patients with DMD experience progressive muscle wasting, difficulty controlling movement, respiratory failure and heart failure leading to full time wheelchair use in teens and early 20’s and reduced life expectancy.

About Locanabio, Inc.
Locanabio is a leader in developing a new class of genetic medicines that has the potential to significantly improve the lives of patients with devastating genetic diseases by correcting the message of disease-causing RNA. Our proprietary platform uses gene therapy to deliver RNA-binding systems, including Cas13d, PUF and snRNA, that can be engineered to selectively manipulate disease-causing RNA by multiple mechanisms. Our systems are designed to provide a durable therapy with a single administration without altering a cell’s DNA. Locanabio’s platform has applications across a range of tissues and diseases, and we are currently advancing programs in rare genetic neuromuscular and neurodegenerative diseases. For more information, visit

SOURCE: Locanabio