CureDuchenne and Avidity Biosciences Hosting Webinar Friday on Potential DMD Therapies

José Lopes, PhD avatar

by José Lopes, PhD |

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CureDuchenne and Avidity Biosciences will host a webinar Friday to brief the Duchenne muscular dystrophy (DMD) community on Avidity’s preclinical development of DMD therapy candidates.

The webinar will take place at 4 p.m. EST and will feature Debra Miller, CureDuchenne’s founder and CEO, and Arthur A. Levin, PhD, Avidity’s executive vice president of research and development. To register, click here.

Avidity is advancing antibody oligonucleotide conjugate (AOC) technology, which uses antibodies to target cells and tissues of interest and improves the cellular delivery of oligonucleotides — short DNA or RNA strands made in the lab. The approach also extends the time these strands remain in circulation compared with oligonucleotides not bound to antibodies.

Combining the cellular and tissue selectivity of antibodies with the precision of oligonucleotide-based therapeutics in AOCs has enabled the modulation of disease-related RNAs in targets such as the muscle, heart, liver, tumors, and immune cells.

AOCs are designed to address a key issue of oligonucleotide approaches for DMD — their delivery for exon skipping to the muscle, diaphragm, and heart.

Exon skipping in DMD refers to skipping over mutated exons — the bits of DNA that contain the information to generate proteins — in the DMD gene. These mutations result from a lack or very limited amount of functional dystrophin protein, which subsequently causes progressive damage and loss of muscle function.

Specifically, Avidity is developing AOCs for DMD patients with mutations in exons 44 and 45. The scientists are currently optimizing the lead sequences.

In a mouse model, AOCs showed an approximately 100-fold greater exon skipping activity than the same oligonucleotide without targeted delivery, according to Avidity. This difference could enable reduced dose levels and dosing frequency, the company noted.

In mice, treatment with a single 10 mg/kg AOC dose led to a 10% increase in dystrophin concentration relative to control mice. In contrast, no dystrophin was detected when a similar dose of unconjugated (without antibody) oligonucleotides was used.

Besides DMD, Avidity intends to use the AOC technology in other rare muscle diseases, including myotonic dystrophy type 1.

Last month, Avidity announced that CureDuchenne, a nonprofit organization, made an equity investment in the company, which will help advance the development of DMD treatment candidates.

“Cure Duchenne has a history of supporting groundbreaking research in Duchenne, and we look forward to working with them, as well as their community of patients, parents, scientists and scientific experts to advance our pipeline of new therapies for boys with this serious disease,” Levin said in a press release at the time.

“CureDuchenne is excited about the future of Avidity’s science and committed to supporting exon skipping development to treat the entire Duchenne population,” Miller said.

Avidity has raised $30 million in venture financing from healthcare investors. In January 2017, the company announced the completion of a $16 million funding round, led by Takeda Pharmaceutical Company, to support the development of AOCs.