Dyne Therapeutics (DYN) AGM presentation summary

Platform overview and delivery strategy

• FORCE platform enables targeted delivery of therapeutic payloads to muscle and CNS using a proprietary Fab against TfR1, with modular payload options including ASO, PMO, and siRNA.

• The platform is investigational and not yet approved by regulatory authorities.

Mechanism and therapeutic rationale

• MAPT (Tau) reduction via siRNA targets tauopathies by decreasing MAPT mRNA, potentially addressing pathological tau mechanisms.

• Approaches include targeting tau production, blocking post-translational modifications, inhibiting aggregation, and promoting clearance.

Conjugate design and preclinical evaluation

• Two conjugates were developed: Conjugate 1 (FORCE Fab) for muscle and CNS, and Conjugate 2 (modified Fab) for enhanced CNS delivery, both using the same MAPT siRNA payload.

• Both conjugates were evaluated in cynomolgus monkeys with systemic administration and MAPT knockdown measured by qPCR.