Entrada Therapeutics (TRDA) H.C. Wainwright 4th Annual BioConnect Investor Conference summary

Technology platform and therapeutic approach

• Endosomal Escape Vehicles (EEVs) are cyclic peptides chemically conjugated to oligonucleotides or proteins, enabling efficient cytosolic delivery for diverse therapeutic applications.

• EEVs achieve about 90% cellular uptake and 50% endosomal escape, significantly improving therapeutic index over previous technologies.

Duchenne muscular dystrophy (DMD) clinical program

• Multi-ascending dose trial in DMD is ongoing, with Cohort 1 at 6 mg/kg showing strong safety and no renal toxicity; Cohort 2 is dosing at 12 mg/kg, with potential to escalate to 18 mg/kg.

• No renal biomarker changes or magnesium disturbances observed in multiple-dose patient cohorts, supporting a favorable safety profile.

• Lower-than-expected dystrophin and exon skipping levels in pediatric patients attributed to lower plasma exposure compared to adults, prompting dose adjustments.

• Efficacy modeling now accounts for lower exposure in pediatric and juvenile NHPs, anticipating a right-shift in efficacy at higher doses.

• Statistically significant improvements in time to rise velocity observed, with functional benefit signals exceeding those of some approved therapies at the lowest dose.

Functional outcomes and mechanistic insights

• Functional benefit, especially time to rise velocity, is prioritized as a key endpoint, aligning with regulatory and clinical expectations.

• Hypothesis suggests early functional gains may result from drug action on satellite cells, enhancing muscle regeneration before mature myofiber uptake.

• Ongoing analyses include nuclear staining to confirm drug presence in satellite cells and open-label extension to assess durability of functional benefit.