Tenaya Therapeutics, Inc. · NASDAQ:TNYA
Tenaya Therapeutics — Technical Presentation (2025)
15 slides from Tenaya Therapeutics's technical presentation, 2025
Slide 1: First Report of MyPEAK-1: a Phase 1b/2a Study of TN-201 in MYBPC3-Associated HCM
First Report of MyPEAK-1: a Phase 1b/2a Study of the Safety and Efficacy of TN-201, An AAV9 Gene Therapy, In Adults With MYBPC3-Associated Hypertrophic Cardiomyopathy Milind Y Desai, MD MBA FACC FAHA FESC Haslam Family Endowed Chair in CV Medicine Vice Chair, HVTI Director, HCM Center, Co-Director,
Slide 2: TN-201: First-in-Class Gene Therapy, Targeting Underlying Cause of Disease
TN-201: First-in-Class Gene Therapy, Targeting Underlying Cause of Disease MYBPC3 Pathophysiology TN-201 Mechanism of Action Heterozygous mutations in the MYBPC3 TN-201 delivers a MYBPC3 Addition of a MYBPC3 gene increases gene lead to ~40% fewer MyBP-C proteins gene to cardiomyocytes using MyBP-C p
Slide 3: MyPEAK-1: A Phase 1b/2a Trial of TN-201 in Adults with MYBPC3-Associated HCM
MyPEAK-1: A Phase 1b/2a Trial of TN-201 in Adults with MYBPC3-Associated HCM Study Objectives Currently Enrolling Cohort 2 • Safety, tolerability • Dose-finding • DSMB Review 1 DSMB Review 2 Pharmacodynamics Cohort 1 Cohort 2 Screening Screening Design N=3 N=3 • Open-label, multi-center, dose- (3E13
Slide 4: Cohort 1 Patients Have More Severe Disease Than the Average HCM Patient
Cohort 1 Patients Have More Severe Disease Than the Average HCM Patient Average HCM Patient 1 Patient 2 Patient 3 Baseline Characteristics Length of Follow-Up - 12 months 12 months 6 months • Significant hypertrophy Gender Male (63%)1 Female Female Male • Symptomatic Phenotype Nonobstructive (72%)1
Slide 5: TN-201 Has Been Well-Tolerated
TN-201 Has Been Well-Tolerated • All patients (n=3) experienced transient, reversible elevations in liver enzymes following dosing • All patients on prophylactic immunosuppression with prednisone and sirolimus • Elevations normalized after additional steroid treatment • One mild adverse event classi
Slide 6: Hematology Measures Stable Up to Year After Dosing
Hematology Measures Stable Up to 1 Year After Dosing Hematology Measures Interim Cohort 1 Hematology Results Platelets • Frequent monitoring throughout ULN=450 450 K/uL 300 150 0 LLN=150 • Patients mostly in normal range with -10 0 10 20 30 40 50 60 minimal changes White Blood Cell Count 15 ULN=11 K
Slide 7: Immunosuppression Is Effective in Managing Response to TN-201
Immunosuppression Is Effective in Managing Response to TN-201 Liver Enzyme Levels & Prednisone Dose Interim Cohort 1 Immunosuppression • Regimen: prophylactic prednisone and sirolimus Patient 1 • Weekly monitoring during taper • Changed management after Patient 1. Immunosuppression shorter and fewer
Slide 8: TN-201 Reaches Heart as Intended and Is Stable Within Cardiomyocytes
TN-201 Reaches Heart as Intended and Is Stable Within Cardiomyocytes TN-201 DNA in Cardiac Biopsy Interim Cohort 1 TN-201 DNA Results Level Seen with Long-Term Stability 2.5 • Patients 1 & 2 biopsies at Weeks 8 and 52 TN-201 DNA copies per genome 2.1 2.1 post-dose. Patient 3 at Week 26; Week 52 fort
Slide 9: TN-201 Expressed in Cardiomyocytes and Continues to Increase Over Time
TN-201 Expressed in Cardiomyocytes and Continues to Increase Over Time TN-201 RNA in Cardiac Biopsy Interim Cohort 1 TN-201 RNA Results 1E+7 • Assay highly specific for TN-201 RNA vs. 13.9x 1.72E+6 1.44x 2.49E+5 patient’s MYBPC3 RNA 1E+6 per microgram of RNA Copies of TN-201 RNA 1.73E+5 1.24E+5 1.87
Slide 10: TN-201 Results in Modest Increase in MyBP-C Protein Levels
TN-201 Results in Modest Increase in MyBP-C Protein Levels MyBP-C Protein Compared to Healthy Controls Interim Cohort 1 MyBP-C Protein Levels 80% • Quantitative assay sensitive, but cannot Patient 1 Patient 2 Patient 3 109% distinguish TN-201-derived protein from % of Normal MyBP-C Protein endogenou
Slide 11: Cardiac Biomarkers Improve or Are Stable by Weeks After Dosing
Cardiac Biomarkers Improve or Are Stable by 52 Weeks After Dosing Cardiac Troponin I Levels Interim Cohort 1 Cardiac Biomarker Levels 80 Patient 1 Patient 2 Patient 3 • Cardiac troponin declined ≥60% in 2 of 3 patients 60 57 53 • Patients 2 and 3 normal or near normal cTnI (ng/mL) 46 42 40 34 • NT-p
Slide 12: Cardiac Structure and Function Have Improved or Are Stable
Cardiac Structure and Function Have Improved or Are Stable LV Mass Index IV Septum Thickness LV Posterior Wall Thickness 250 Patient 1 Patient 2 Patient 3 2.6 Patient 1 Patient 2 Patient 3 2.1 Patient 1 Patient 2 Patient 3 203 2.34 2.14 1.63 1.78 200 2.1 174 1.95 1.98 1.6 189 1.82 178 1.95 g/m2 1.26
Slide 13: All Patients' Heart Failure Symptoms Improved and Are Now NYHA Class I
All Patients’ Heart Failure Symptoms Improved and Are Now NYHA Class I NYHA Class Interim Heart Failure Symptoms in Cohort 1 Patient 1 Patient 2 Patient 3 • All patients symptomatic at baseline Class IV 4 • All patients’ NYHA Class improved by Week NYHA Class Class III 3 26 Class 2II • No limitation
Slide 14: Conclusions and Future Directions
Conclusions and Future Directions • First-ever clinical data for gene therapy for HCM • Gene therapy can be administered and managed effectively at an HCM center • TN-201 at 3E13 vg/kg has been well tolerated • Robust transduction and expression at 3E13 vg/kg dose (Cohort 1) • Biomarkers and measure
Slide 15: Acknowledgments
Acknowledgments • Patients and their families • Cleveland Clinic site staff and colleagues - Dr. Pavan Bhat, Danielle Kellner RN NP and Sue Ospina RN NP • Fellow MyPEAK-1 investigators • Team at Tenaya - Dr. Whit Tingley, LaTanya Tomlinson RN, Dr. Bardha Varfaj, Dr. Matt Pollman, Dr. Gretchen Argast