Slide 1: RIDGE-1 Phase 1b/2 Clinical Trial of TN-401 gene therapy for PKP2-Associated ARVC
RIDGE-1 Phase 1b/2 Clinical Trial of TN-401 gene therapy for the potential treatment of PKP2-Associated ARVC May 15, 2026
Slide 2: Forward-looking statement
Forward-looking statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our management’s beliefs and assumptions and on information currently availabl
Slide 3: Today's speakers and agenda
Today’s speakers and agenda Agenda Introductory remarks Faraz Ali RIDGE-1 objectives Whit Tingley Faraz Ali, MBA Kathy Ivey, Ph.D., Clinical findings Whit Tingley Chief Executive Officer Senior Vice President, Research Biopsy results Kathy Ivey Safety findings Whit Tingley Clinician perspective Q&A
Slide 4: Advancing TN-201 and TN-401 towards pivotal studies
IMMEDIATE OPPORTUNITY: Advancing TN-201 and TN-401 towards pivotal studies Large market potential in rare Early evidence of clinically Planned data readouts offer Seeking regulatory clarity on disease setting meaningful benefit multiple de-risking catalysts in approvable endpoints and 2026 pivotal t
Slide 5: Interim RIDGE-1 Cohort 1 & 2 Data Highlights
HIGHLIGHTS Interim RIDGE-1 Cohort 1 & 2 Data 1 CLINICAL: All patients on study achieved consistent and meaningful reductions in arrhythmia burden that were sustained up to 1 year for Cohort 1 2 BIOPSY: TN-401 is reaching cardiomyocytes and achieving expression 3 SAFETY: TN-401 was well tolerated at
Slide 6: PKP2-associated ARVC is estimated to affect >70,000 people in the U.S.
SUBSTANTIAL UNMET NEED PKP2-associated ARVC is estimated to affect >70,000 people in the U.S.(1) ARVC is a severe and progressive genetic heart disease lacking therapeutic treatment options ARVC HEART >15% of heart-related deaths in patients < 35 are due to Unstable ARVC(1) connections and scar tiss
Slide 7: RIDGE-1 Interim Data Readout: Trial Objectives
RIDGE-1 Interim Data Readout: Trial Objectives
Slide 8: TN-401 gene therapy for PKP2-associated ARVC
MECHANISM TN-401 gene therapy for PKP2-associated ARVC PKP2+ Pathophysiology TN-401 Mechanism of Action Desmosome and Gap Junctions in Treated with TN-401 PKP2-associated ARVC Heart Missing TN-401 PKP2 PKP2 cassette protein AAV9 capsid Desmosome Desmosome structure in structural disarray integrity G
Slide 9: RIDGE-1 Phase 1b/2 clinical trial
TRIAL DESIGN RIDGE-1 Phase 1b/2 clinical trial Treatment goal: demonstrate reduction in arrhythmic events Study Objectives Design • Safety and tolerability • Open-label, multi-center dose-escalation and dose-expansion • Dose-finding • 52-week study period with four-year follow-up • Pharmacodynamics
Slide 10: RIDGE-1 patients' arrhythmia burden more severe than broader PKP2+ population
SCREENING CHARACTERISTICS RIDGE-1 patients’ arrhythmia burden more severe than broader PKP2+ population Average Cohort 1 (3E13 vg/kg) Cohort 2 (6E13 vg/kg) PKP2+ Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 patient1 Follow-Up - 52 weeks 52 weeks 40 weeks 32 weeks 26 weeks 20 weeks Gen
Slide 11: RIDGE-1 Readout: TN-401's Impact on Arrhythmia Burden
RIDGE-1 Readout TN-401’s Impact on Arrhythmia Burden
Slide 12: All patients had meaningful reductions in PVC burden post-TN-401
CLINICAL RESULTS All patients had 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 P
Slide 13: Patients with high NSVT burden had dramatic reductions over time
CLINICAL RESULTS 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 • Pat
Slide 14: PVC and NSVT burden are key indicators of electrical instability and risk
VENTRICULAR ARRHYTHMIA RISK FACTORS PVC and NSVT burden are key indicators of electrical instability and risk of life-threatening events Frequency Severity PVCs NSVTs SVTs VFs SCA Premature Ventricular Non-Sustained Ventricular Sustained Ventricular Ventricular Sudden Cardiac Contractions Tachycardi
Slide 15: RIDGE-1 Readout: TN-401 Heart Biopsy Findings
RIDGE-1 Readout TN-401 Heart Biopsy Findings
Slide 16: Tracking gene therapy's delivery to the heart
BIOPSY MEASURES Tracking gene therapy’s delivery to the heart TN-401 Upon Infusion 1 2 3 DELIVERY: EXPRESSION: EXPRESSION: Transduction (DNA) Transcription (RNA) Translation (Protein) TN-401 enters cardiomyocytes. TN-401’s healthy copy of TN-401 mRNA is then Healthy copy of PKP2 gene PKP2 gene is tr
Slide 17: TN-401 DNA levels show robust cardiac transduction across both doses
BIOPSY RESULTS TN-401 DNA levels show robust cardiac transduction across both doses Post-Dose TN-401 DNA Levels by Patient 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 Patient 2 Patient 3 P
Slide 18: TN-401-specific RNA levels demonstrate PKP2 expression in all patients
BIOPSY RESULTS TN-401-specific RNA levels demonstrate PKP2 expression in all patients Post-Dose TN-401 RNA Levels by Patient Cohort 1 TN-401 mRNA Levels Cohort 2 TN-401 mRNA 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
Slide 19: Assessment of TN-401 protein expression
BIOPSY RESULTS Assessment of TN-401 protein expression PKP2 Protein Levels Over Time in Cohorts 1 and 2 Cohort 1 Protein Levels Cohort 2 Protein Levels* Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 0.0070 • Measured LC-MS assay for PKP2 15% protein (normalized to MYH protein) PKP2 / MYH Peptide
Slide 20: Variability of biopsy samples from ARVC hearts creates methodological challenges
METHODOLOGY MATTERS Variability of biopsy samples from ARVC hearts creates methodological challenges to quantify PKP2 protein PKP2-associated ARVC patients have fibrofatty Biopsy composition of each patient can replacement and fibrosis spread across the myocardium vary significantly from pinch-to-pi
Slide 21: Tenaya approach to quantifying changes in PKP2 protein levels
METHODOLOGY MATTERS Tenaya approach to quantifying changes in PKP2 protein levels selected to reduce variability PKP2 protein levels vary greatly across individuals1 Use of LC-MS + normalizing to myosin heavy chain complicate interpretation and comparisons reduces variable factors • PKP2 protein may
Slide 22: RIDGE-1 Readout: TN-401 Safety and Tolerability
RIDGE-1 Readout TN-401 Safety and Tolerability
Slide 23: Both TN-401 doses equally well tolerated
SAFETY OBSERVATIONS Both TN-401 doses equally well tolerated Majority of TN-401-related AEs mild, asymptomatic and manageable • Cohort 1 AEs previously disclosed Cohort 1* Cohort 2 Relevant (3E13 vg/kg; n=3) (6E13 vg/kg; n=3) • Cohort 2 AEs include two grade 3 AEs in the Adverse Event same patient d
Slide 24: Immunosuppression regimen successfully managed immune response at both doses
SAFETY OBSERVATIONS Immunosuppression regimen successfully managed immune response at both doses Duration & Mean Daily Corticosteroid Dose Mean Daily Dose (mg/day) Patient 1 21.4 32.1 (3E13 vg/kg) • Prophylactic prednisone and sirolimus Cohort 1 Patient 2 24.3 26.9 successful in managing immune resp
Slide 25: RIDGE-1 in Context: Clinician Conversation
RIDGE-1 in Context Clinician Conversation
Slide 26: Closing remarks
7’ TENAYA THERAPEUTICS Closing remarks
Slide 27: Acknowledgments
Acknowledgments • RIDGE-1 patients and their families • Drs. John Giudicessi, Vasanth Vedantham, Matthew Taylor, Andreas Barth and other 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 Universit
Slide 28: RIDGE the largest natural history study of PKP2+ ARVC in the world
COMMITTED TO THE PKP2 COMMUNITY RIDGE the largest natural history study of PKP2+ ARVC in the world Largest Ever PKP2+ ARVC …Collecting Data …Directly Feeding Natural History Study… Across Domains… RIDGE-1 Trial • All RIDGE-1 participants to date were identified through RIDGE >185 >2,500 • RIDGE info
Slide 29: 2026 anticipated program milestones
2026 anticipated program milestones TN-201 for MYBPC3-associated HCM • Enroll 6E13 vg/kg expansion cohort 1H • MyPEAK-1 interim Cohort 2 data • MyPEAK-1 ~2-year Cohort 1 and ~52-week Cohort 2 data 2H • Continue MyPEAK-1 enrollment • Pursue regulatory alignment on pivotal plans TN-401 for PKP2-associ
Slide 30: Q&A
Q&A s< > “< y 4 at THERAPEUTIC