Entrada Therapeutics (TRDA) 7th Annual Evercore ISI HealthCONx Conference summary

Clinical development updates

• Healthy volunteer trial in the UK for ENTR-601-44 showed strong data, exceeding expectations, and supports global regulatory filings in Q4 for both ENTR-601-44 and ENTR-601-45, aiming for phase 2b MAD studies and potential accelerated approval.

• The FDA clinical hold did not impact program progress; transition from healthy volunteers to patient studies is underway, with ex-U.S. phase 2 starts likely to precede U.S. starts due to regulatory timelines.

• Patient phase 2 trials are expected to begin next year, with submissions guided for Q4 this year.

• By the end of next year, three patient MAD phase 2 trials (exons 44, 45, and 50) are expected to be ongoing, with a fourth EEV program in the clinic if including the VX-670 program.

• Trial design and timing of data readouts will be finalized after regulatory feedback, with more details to be shared once protocols are coordinated globally.

Safety and efficacy insights

• No renal toxicity or concerning biomarkers observed at 6 mg/kg in phase 1; higher excretion rates in humans reduce risk of proximal tubule damage compared to non-human primates.

• The EEV peptide used in neuromuscular programs provides consistent biodistribution and PK profiles across compounds, supporting confidence in platform safety and efficiency.

• Dose-dependent increase in exon skipping observed in healthy volunteers, with significant effect at 6 mg/kg; response is non-linear, with higher doses expected to yield exponential increases.

• Exon skipping in healthy volunteers is not directly comparable to patients due to biological differences; patient-derived myofibers show 20–40x higher exon skipping than normal.

• Dystrophin measurement, rather than exon skipping, will be the primary focus in patient biopsies, with timing aligned to field standards (typically over a month post-dose).

Platform and pipeline strategy

• The EEV platform demonstrates consistent PK and biodistribution regardless of oligo cargo, streamlining trial design and non-clinical planning for future programs.

• Differences in exon skipping efficiency across targets (e.g., exon 44 vs. 51) may require modestly different dosing, driven by underlying biology rather than distribution.

• Cash runway extends into 2027, supporting all three DMD phase 2 trials and potentially a registrational trial before additional fundraising is needed.

• Business development opportunities are considered if they align with platform advancement and operational capacity, with a disciplined approach to new partnerships.