4DMT Presents Interim Data from 4D-310 INGLAXA Phase 1/2 Clinical Trials for Fabry Disease Cardiomyopathy at WORLDSymposium 2024 - Seite 2

“These promising clinical results continue to validate our Therapeutic Vector Evolution platform, as well as the potential of the C102 vector for targeted IV delivery to cardiomyocytes. Cardiac biopsies also showed robust and durable delivery and transgene expression from 4D-310, and remarkably, a reduction in Gb3 substrate in cardiomyocytes,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “No approved therapy has been shown to definitively clear accumulated Gb3 from cardiomyocytes in patients with Fabry disease, which speaks to 4D-310’s highly differentiated profile. We remain on-track to submit results from the non-clinical study to evaluate 4D-310 in NHPs with the R/S immunosuppressive regimen to the FDA in Q2 2024 to address the clinical hold.”

INGLAXA Phase 1/2 Clinical Trial Design & Enrollment

• Dose escalation and dose expansion trial assessing a single IV infusion of 4D-310 in a broad and diverse Fabry disease patient population
• Enrolled six patients, each treated with 1E13 vg/kg of 4D-310 and a prophylactic corticosteroid immunosuppressive regimen
  • Protocol amended to change immunosuppressive regimen to rituximab and sirolimus (enrollment on this amendment pending)
• Cardiac biopsies allowed at week 6 and 26 in the INGLAXA-2 trial (to date, one patient had biopsies performed)

INGLAXA Phase 1/2 Interim Data Summary (Data Cutoff: December 5, 2023)

• Safety and Tolerability
  • Previously reported cases of aHUS (n=3) have fully resolved
  • No clinically significant cardiac or liver toxicities
  • No new 4D-310–related adverse events > Grade 1 since the last interim update in February 2023
• Echocardiography Contractility Assessments (Global Longitudinal Strain, GLS)
  • Improved GLS in all five evaluable patients by month 12
  • Two patients who reached 24 months of follow-up both showed clinically meaningful improvement with change from baseline exceeding the minimal detectable difference of -1.5% (-2.8 and -2.9%, respectively)
• Cardiopulmonary Exercise Testing (CPET) Peak VO₂ Assessments
  • 3 of 4 evaluable patients demonstrated clinically meaningful improvement by CPET peak VO₂ with change from baseline exceeding the minimal clinically important difference (MCID) of +1.5 at month 12 (+1.8, +2.0 & +7.0)
  • One patient who reached 24 months of follow up continued to show meaningful improvement with change from baseline exceeding the MCID of +1.5 (+7.8)
• Cardiac Quality of Life Assessments (Kansas City Cardiomyopathy Questionnaire)
  • Two patients had low baseline scores <90 (scale 0-100); both patients had clinically meaningful improvements in QOL (exceeding the MCID of +5)
    • One patient had 12 months follow-up: Clinical & Overall Summary Scores improved by +5.7 and +11.7, respectively
    • One patient had 24 months follow-up: Clinical & Overall Summary Scores improved by +12.5 and +8.3, respectively
  • Three patients had baseline values >90 (92.7, 100 & 100); all remained stable through 12-24 months (+1.1 to -1.6).
• Cardiac Biopsy Assessments of Transgene Expression and Substrate Clearance
  • Cardiac biopsies at week 6 and 26 from one patient showed robust & durable 4D-310–mediated transgene expression in cardiomyocytes
    • All samples positive for transgene RNA (ISH) & AGA protein (IHC)
    • At week 26, mean Gb3 inclusion body volume per cardiomyocyte was reduced 15% from week 6 and 61% vs. historical sample collected approximately 7 years prior to enrollment and analyzed independently by investigator