Tenaya Therapeutics, Inc. · NASDAQ:TNYA
Tenaya Therapeutics — ASGCT 2026
13 slides from Tenaya Therapeutics's conference presentation, May 15, 2026
Slide 1: Interim Data from RIDGE-1: Phase 1b/2 Study of TN-401 in PKP2+ ARVC
INTERIM DATA FROM RIDGETM-1: A PHASE 1B/2 STUDY OF TN-401, AN AAV9 INVESTIGATIONAL GENE THERAPY, IN ADULTS WITH PKP2+ ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC) John M. Giudicessi, MD, PhD | Mayo Clinic Vasanth Vedantham, MD, PhD | University of California, San Francisco Matthew Taylor,
Slide 2: PKP2+ ARVC: An Autosomal Dominant Disease Resulting in Life-Threatening Arrhythmias
PKP2+ ARVC: AN AUTOSOMAL DOMINANT DISEASE, RESULTING IN LIFE-THREATENING ARRHYTHMIAS PKP2+ ARVC Pathophysiology… …Results in Severe Arrhythmia Burden • Plakophilin (PKP2) is a structural protein required for normal heart development and performance have more than 500 PVCs per 90% day, despite standa
Slide 3: AAV:PKP2 Gene Replacement Therapy
ADENO-ASSOCIATED VIRUS (AAV):PKP2 GENE REPLACEMENT THERAPY PKP2 haploinsufficiency AAV construct with PKP2 gene inserted* AAV9 containing (reduced plakophilin 2 levels) PKP2 Codon Optimized WPRE Poly PKP2 gene Cardiac Promoter A Missing PKP2 *AAVs are naturally occurring, non-integrating viruses tha
Slide 4: RIDGE-1: Phase 1b/2 Trial of TN-401 in Adults with PKP2+ ARVC
RIDGE-1: PHASE 1B/2 TRIAL OF TN-401 IN ADULTS WITH PKP2+ ARVC Treatment goal: Demonstrate Reduction in Arrhythmic Events Study Objectives Design • Safety and tolerability • Open-label, multi-center dose-escalation and dose-expansion Enrolling at 9 sites in • Dose-finding • 52-week study period with
Slide 5: RIDGE-1 Patients' Arrhythmia Burden More Severe Than Broader PKP2+ ARVC Population
RIDGE-1 PATIENTS’ ARRHYTHMIA BURDEN MORE SEVERE THAN BROADER PKP2+ ARVC POPULATION Screening Characteristics of RIDGE-1 Participants More severe Avg. NHx Cohort 1 (3E13 vg/kg) Cohort 2 (6E13 vg/kg) vs. average PKP2+ Pt1 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Follow-Up - 52 weeks
Slide 6: Both TN-401 Doses Equally Well Tolerated
BOTH TN-401 DOSES EQUALLY WELL TOLERATED Summary of Safety, Tolerability, and Immunosuppression Across Cohorts 1 and 2 • Majority of TN-401-related AEs have been mild, Cohort 1* Cohort 2 asymptomatic, and manageable Relevant (3E13 vg/kg; n=3) (6E13 vg/kg; n=3) Adverse Event • Cohort 1 AEs have been
Slide 7: TN-401 DNA Levels Show Robust Cardiac Transduction Across Both Doses
TN-401 DNA LEVELS SHOW ROBUST CARDIAC TRANSDUCTION ACROSS BOTH DOSES TN-401 DNA Levels at 1st Post-Dose Biopsy by Patient in Cohorts 1 and 2 Cohort 1 Mean = 3.4 vg/dg Cohort 2 Mean = 3.8 vg/dg* • Assay for assessing DNA levels specific to TN-401 vector genome TN-401 Vector Genomes per Patient 1 Pati
Slide 8: TN-401 RNA Levels Show Cardiac PKP2 Expression in All Patients
TN-401 RNA LEVELS SHOW CARDIAC PKP2 EXPRESSION IN ALL PATIENTS Post-Dose TN-401 RNA Levels by Patient in Cohorts 1 and 2 Cohort 1 TN-401 RNA Levels Cohort 2 TN-401 RNA Levels* • Assay for TN-401 RNA is specific to TN-401 (vs. endogenous) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 TN-401 RNA C
Slide 9: Assessment of TN-401 Protein Expression Complicated by Biopsy Sample Variability
ASSESSMENT OF TN-401 PROTEIN EXPRESSION COMPLICATED BY BIOPSY SAMPLE VARIABILITY PKP2 Protein Levels Over Time in Cohorts 1 and 2 Cohort 1 Protein Levels Cohort 2 Protein Levels* • LC-MS assay quantifies total PKP2 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 protein level, normalized to a 0.00
Slide 10: All Patients Had Clinically Meaningful Reductions in PVC Burden Post-TN-401
ALL PATIENTS HAD CLINICALLY MEANINGFUL REDUCTIONS IN PVC BURDEN POST-TN-401 Change in Daily PVC Rate from Screening to Most Recent Visit Cohort 1 Average = 60% Reduction Cohort 2 Average = 67% Reduction • PVCs assessed by 7-day continuous ECG Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient
Slide 11: Patients with High NSVT Burden Had Dramatic Reductions Over Time
PATIENTS WITH HIGH NSVT BURDEN HAD DRAMATIC REDUCTIONS OVER TIME Change in Daily NSVT Rate from Screening to Most Recent Visit Cohort 1 (3E13 vg/kg) Cohort 2 (6E13 vg/kg) • NSVT burden assessed Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 by 7-day continuous ECG • Patients 2 & 5 saw m
Slide 12: Conclusions
CONCLUSIONS Enrolled patients are more Patients had clinically severe, electrically unstable meaningful reductions in PVCs, than broader PKP2+ ARVC, NSVTs after TN-401 treatment despite standard of care TN-401 well tolerated across These data support 3E13 vg/kg and 6E13 vg/kg continued development o
Slide 13: Acknowledgments
ACKNOWLEDGMENTS • RIDGE-1 patients and their families • Drs. Vasanth Vedantham, Matthew Taylor, Andreas Barth and fellow RIDGE-1 investigators • Members of the DSMB: Dr. Barry Greenberg, Dr. Gary Lipshutz, Ena Bromley, PhD, and Dr. James Lewis • Michael Previs, PhD, and the University of Vermont tea