Precision BioSciences (DTIL) H. C. Wainwright Genetic Medicines Virtual Conference summary

ARCUS gene-editing platform overview

• ARCUS is derived from homing endonucleases, not CRISPR, offering unique advantages in gene editing.

• Key benefits include a staggered DNA cut for efficient repair, compact size for delivery, and single-component simplicity.

• Small size enables delivery of two nucleases in one AAV, crucial for targeting muscle tissue in DMD.

PBGENE-DMD program rationale and design

• DMD was prioritized due to high unmet need and ARCUS's competitive advantages in this indication.

• PBGENE-DMD targets the exon 45-55 hotspot, applicable to up to 60% of DMD patients.

• Two ARCUS nucleases excise the hotspot, restoring near full-length dystrophin.

• All-in-one AAV delivery overcomes limitations of multi-vector CRISPR approaches.

Differentiation from other therapies

• Broader applicability than single-exon CRISPR or exon-skipping, which serve only small patient subsets.

• Restores near full-length dystrophin, unlike microdystrophin gene therapies that deliver truncated proteins.

• One-time treatment with durable effect, compared to repeated dosing required for exon-skipping.