Tenaya Therapeutics, Inc. · NASDAQ:TNYA
Tenaya Therapeutics — Investor Presentation (April 2025)
50 slides from Tenaya Therapeutics's investor presentation, April 2025
Slide 1: Scaling new heights in the fight against heart disease
Scaling new heights in the fight against heart disease April 2025
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: Our purpose
Our purpose: To transform and extend lives through the discovery, development and delivery of potentially curative therapies that target the underlying causes of heart disease. 3
Slide 4: Singular focus on the heart
Singular focus on the heart 3 clinical-stage programs and multiple near-term gene therapy data readouts Deep expertise in cardiology, genetics and rare disease drug development Foundational capabilities fuel innovation and first-in-class potential Track record of execution on ambitious goals 4
Slide 5: Clinical-stage pipeline poised for progress
Clinical-stage pipeline poised for progress U.S. Development Program Modality Status Prevalence Stage Clinical-Stage Programs Cohort 1 enrolled MyPEAK -1 Phase 1b/2 TN-201 for MYBPC3+ HCM Cohort 2 enrolling • FDA Orphan Drug, Fast Track and Rare Pediatric Disease designations AAV9 gene Completed > 1
Slide 6: ACC.25 Cohort 1 Update: Positive early signals of TN-201's clinical impact
ACC.25 Cohort 1 Update: Positive early signals of TN-201’s clinical impact 1 Safety: TN-201 well tolerated at 3E13 vg/kg dose; safety profile is consistent with other gene therapies • No cardiotoxicities • Liver enzyme elevations manageable and reversible • All patients have completed every visit an
Slide 7: Global clinical execution is building momentum for TN-201 and TN-401
Global clinical execution is building momentum for TN-201 and TN-401 Broad clinical footprint positions current and future genetic therapy programs for success interventional, non- >400 study participants 5 interventional and/or natural history studies ~45 clinical sites activated 8 countries Prov
Slide 8: Significant clinical progress expected in 2025 and beyond
Significant clinical progress expected in 2025 and beyond 1H’25 2H’25 2026+ TN-201 • 1H’26: Present two-year Cohort 1 Present additional Cohort 1 • Provide Cohort 1 data and one-year Cohort 2 data MyPEAK-1 data update & present initial • Pursue regulatory alignment on • Complete Cohort 2 enrollmen
Slide 9: Increasing clinical and regulatory momentum across the sector
Increasing clinical and regulatory momentum across the sector bodes well for the future Growing number of AAV gene therapy sponsors Cardiomyopathy clinical guidelines recommend have announced regulatory alignment on pivotal genetic testing in the U.S. and Europe studies or approvals based on surroga
Slide 10: TN-201 for MYBPC3-associated HCM
TN-201 for MYBPC3-associated HCM
Slide 11: MYBPC3-associated HCM is estimated to affect 120,000 people in the U.S.
MYBPC3-associated HCM is estimated to affect 120,000 people in the U.S. alone(1) A severe and progressive autosomal dominant condition affecting adults, teens, children and infants HCM HEART ~57% ofvariants identified genetic underlying familial HCM are MYBPC3 mutations(2) Thickened left ventricle •
Slide 12: Patients with MYBPC3+ HCM are at high risk for serious cardiac events
Patients with MYBPC3+ HCM are at high risk for serious cardiac events(1) Younger onset correlates with greater rates of morbidity and mortality SHaRE analyses of 1,637 adults with MYBPC3-associated HCM 50% ofexperience adults diagnosed before age 40 a serious cardiac event by age 50 Cohort 1: Age 18
Slide 13: TN-201 is the first gene therapy being developed for MYBPC3-associated HCM
TN-201 is the first gene therapy being developed for MYBPC3-associated HCM(1) MYBPC3+ Pathophysiology TN-201 Mechanism of Action • MyBP-C is an essential structural protein • TN-201 targets the • Addition of a MYBPC3 gene increases regulating cardiac contractility via underlying genetic cause of MyB
Slide 14: Single dose of TN-201 in preclinical KO mouse model reversed disease
Single 3E13 vg/kg dose of TN-201 in preclinical KO mouse model reversed disease and increased survival Reduced heart Extended Improved heart mass survival function (8(8Months MonthsPost-Treatment) Post-Treatment) (20 Months Post-Treatment) Multiple hallmarks of disease LV Mass/ Body Weight (mg/g) Pr
Slide 15: MyPEAK-1 Phase 1b/2 clinical trial design
MyPEAK-1 Phase 1b/2 clinical trial design Initial Cohort 2 + additional Cohort 1 data in 2H’25 Study Objectives • • Safety, tolerability Dose-finding Cohort 1 DSMB review 2 DSMB review 1 Cohort 2 N=3 Screening Screening • Pharmacodynamics N=3 (3E13 vg/kg) (6E13 vg/kg) Design Patients dosed Pat
Slide 16: MyPEAK-1 Phase 1b/2 clinical endpoints
MyPEAK-1 Phase 1b/2 clinical endpoints Seeking directional consistency across multiple parameters over time with the goal of halting or even reversing steady disease progression Study Endpoints Over Time Post-Gene Therapy Safety and tolerability Pharmacokinetics (PK) Transgene uptake and expression
Slide 17: Interim MyPEAK-1 Data from Cohort 1
Interim MyPEAK-1 Data form Cohort 1 C O N F ID E N T IAL
Slide 18: MyPEAK-1 Cohort 1 patients younger and more severe than average HCM patient
MyPEAK-1 Cohort 1 patients younger and more severe compared to average HCM patient Average HCM Patient 1 Patient 2 Patient 3 Length of Follow-Up - 12 months 12 months 6 months Gender Male (63%)1 Female Female Male Phenotype Nonobstructive (72%)1 Nonobstructive Nonobstructive Nonobstructive Current A
Slide 19: TN-201 was generally well tolerated at 3E13 vg/kg dose
TN-201 was generally well tolerated at 3E13 vg/kg dose Reported AEs consistent with other AAV gene therapies and known effects of immunosuppression IS regimen effectively managed response to TN-201 Patients initiated prophylactic IS of prednisone and sirolimus pre-dose Reversible elevated liver
Slide 20: TN-201 demonstrates robust and durable cardiac transduction
TN-201 demonstrates robust and durable cardiac transduction at 3E13 vg/kg dose TN-201TN-201 DNA inVCN Cardiac Biopsy surpasses TN-201 preclinical efficacy threshold and VCN surpasses preclinical compares favorably to peer efficacy threshold and compares 2.5 favorably to peer Long-term stability achi
Slide 21: TN-201 RNA expressed in cardiomyocytes and increases over time
TN-201 RNA expressed in cardiomyocytes and continues to increases over time TN-201 RNA in Cardiac Biopsy TN-201 RNA expression TN-201increased RNA expression by as increases much as 13-fold TN-201 1E+7 13.9x 1.7E+06 over time and preclinical level performs from week similarly 8 to Weekto 52 1.4x 2.5
Slide 22: MyBP-C protein levels vary between healthy and MYBPC3+ HCM populations
MyBP-C protein levels vary between healthy and MYBPC3+HCM populations and between individuals Range of MyBP-C protein levels in Treatment goal = Increase MyBP-C levels MYBPC3-associated HCM and healthy controls(1) from patient’s own baseline • MYBPC3-associated HCM patients exhibit Max = 109% ~40% l
Slide 23: TN-201 treatment results in modest increase in MyBP-C protein levels
TN-201 treatment results in modest increase in MyBP-C protein levels Changes in both mRNA and protein levels suggest TN-201 is being transcribed and expressed MyBP-C Protein Compared to Healthy Controls Protein levels increase over time 80% between 8- and 52-week biopsies Patient 1 Patient 2 Patient
Slide 24: Cardiac biomarkers improved or stabilized
Cardiac biomarkers improved or stabilized Cardiac Troponin Levels Interim Cohort 1 TN-201 Biomarker Results Cardiac troponin is a biomarker in the blood that indicates injury to heart cells; associated with increased risk of adverse events • Cardiac troponin improved by ≥60%, to normal or near norma
Slide 25: Improvements observed in measures of hypertrophy
Improvements observed in measures of hypertrophy Posterior Wall Thickness Interim Cohort 1 TN-201 Hypertrophy Results Echo measurements of heart mass and thickness were taken to assess changes • 2 of 3 patients saw improvements in one or more measures of hypertrophy • Left ventricular posterior wall
Slide 26: Symptoms of heart failure improved in all Cohort 1 patients
Symptoms of heart failure improved in all Cohort 1 patients NYHA Classification Interim Cohort 1 TN-201 NYHA Results NYHA classification is used to categorize the severity of heart failure based on symptoms and physical activity • Before treatment, all patients were symptomatic during ordinary physi
Slide 27: Future directions
Future directions C O N F ID E N T IAL
Slide 28: Plan to explore TN-201 in the full spectrum of MYBPC3 patient presentation
Plan to explore TN-201 in the full spectrum of patient presentation caused by MYBPC3 mutations Adults Adolescents Peds Infants Heterozygotes Homozygotes Non-Obstructive Phenotype Obstructive Phenotype (70%) (30%) • Adults (18-65) with MYBPC3 mutation • Nonobstructive or obstructive HCM • NYHA class
Slide 29: MYBPC3-associated pediatric patients represent sizable severe population
MYBPC3-associated pediatric patients represents sizable severe population lacking therapeutic options Pediatric-onset patients experience a markedly greater disease progression and cumulative disease burden vs. adult-onset patients (1) more likely to develop life-threatening TN-201 granted FDA Rare
Slide 30: TN-401 for PKP2-associated ARVC
TN-401 for PKP2-associated ARVC
Slide 31: PKP2-associated ARVC is estimated to affect >70,000 people in the U.S.
PKP2-associated ARVC is estimated to affect >70,000 people in the U.S.(1) A severe and progressive genetic heart disease lacking therapeutic treatment options • Early symptoms include palpitations, lightheadedness, of heart-related deaths in fainting (1) >15% patients < 35 are due to ARVC(2) • Signi
Slide 32: TN-401 gene therapy for PKP2-associated ARVC
TN-401 gene therapy for PKP2-associated ARVC Underlying problem Tenaya Approach • Mutations of the PKP2 gene lead to lower levels • Target the underlying genetic cause of disease of Plakophilin-2 (PKP2) protein(1) • Deliver a working PKP2 gene utilizing AAV9 capsid • PKP2 is an essential structural
Slide 33: AAV9 capsid comes with robust validation from preclinical and clinical studies
AAV9 capsid comes with robust validation from preclinical efficacy and clinical studies Outperforms other serotypes in head-to-head preclinical models of mice and NHPs Mouse Model Non-Human Primate Model Viral RNA Viral Protein Viral RNA Viral DNA Transduction Transgene Expression All heart cells Tr
Slide 34: 3E13 vg/kg dose restored PKP2 and other desmosomal proteins to normal levels
3E13vg/kg dose restored PKP2 and other desmosomal proteins to normal levels Pkp2-cKO Mice Plakophilin-2 (PKP2) Desmoplakin (DSP) Protein Expression Protein Expression Relative Protein Expression Relative Protein Expression Yang, et al, ASGCT 2022 34
Slide 35: TN-401 in preclinical KO mouse model reverses hallmarks of disease
Single 3E13 vg/kg dose of TN-401 in preclinical KO mouse model reverses hallmarks of disease and extends survival Reversal of Reduction of Improved survival arrhythmia RV enlargement Survival Benefit Pkp2-cKO Mice Yang, et al, ASGCT 2022 35
Slide 36: RIDGE-1 Phase 1b clinical trial for PKP2-associated ARVC
RIDGE-1 Phase 1b clinical trial for PKP2-associated ARVC Initial Cohort 1 data anticipated in 2H’25 Study Objectives • Safety and tolerability • Dose-finding Cohort 1 DSMB review 2 DSMB review 1 Cohort 2 • Pharmacodynamics N=3 Screening Screening N=3 (3E13 vg/kg) (6E13 vg/kg) Design Patients dosed P
Slide 37: RIDGE-1 Phase 1b endpoints
RIDGE-1 Phase 1b endpoints Treatment goal: demonstrate reduction in arrhythmic events Initial data in 2025 to include safety and biopsy results at low-dose Study Endpoints Over Time Post-Gene Therapy Safety and tolerability Pharmacokinetics (PK) Transgene uptake and expression Pharmacodynamics (PD)
Slide 38: TN-301 HDAC6 inhibitor for HFpEF
TN-301 HDAC6 inhibitor for HFpEF
Slide 39: TN-301 small molecule HDAC6 inhibitor for HFpEF
TN-301 small molecule HDAC6 inhibitor for HFpEF HFpEF remains the largest unmet need in heart disease estimated to affect >3M in the U.S. alone(1, 2) • Characterized by diastolic dysfunction • Multiple contributing risk factors driven by stiffening of heart ventricles resulting in complex pathophysi
Slide 40: TN-301 small molecule HDAC6 inhibitor for HFpEF
TN-301 small molecule HDAC6 inhibitor for HFpEF Phase 1 complete; Optimally suited for development by/with a partner About HFpEF Tenaya Approach Key Advantages • Disease driven by multi-factorial • Designed to specifically inhibit HDAC6 • High selectivity (1000x fold) offers processes involving many
Slide 41: Completed Phase 1 trial of TN-301 in healthy participants
Completed Phase 1 trial of TN-301 in healthy participants TN-301 was generally well tolerated across broad dose ranges • SAD (1mg – 700mg) and MAD (25mg, 100 mg, 300 mg for 14 days) • Most AEs were GI related; occurred with similar frequency in placebo group and did not increase with dose Target eng
Slide 42: HDAC6 inhibitor demonstrates preclinical potential as single-agent or with SGLT2 inhibitor
HDAC6 inhibitor demonstrates preclinical potential for use as single-agent or in combination with SGLT2 inhibitor Comparable efficacy Additive efficacy as a single agent in combination HDAC6 vs. SGLT2(1) HDAC6 + SGLT2(2) E/e` LVEDP E/e` LVEDP LVEDP(mmHg) E/e' Ratio HDAC6 inhibitor demonstrates great
Slide 43: Capabilities
yA TENAYA THERAPEUTICS Capabilities
Slide 44: Modality-agnostic target and drug discovery
Modality-agnostic target and drug discovery that aims to address the underlying problem HCM ARVC HFpEF DCM MI HFrEF DCM Underlying MYBPC3 PKP2 Multi- PLNR14del Loss of Decrease in Unknown problem mutation mutation factorial mutation heart cells SERCA2a mutation(s) Tenaya Gene Gene Small Gene Cellula
Slide 45: Proprietary internal capabilities and know-how generating differentiated assets
Proprietary internal capabilities and know-how generating differentiated, next-gen assets Novel cardiac-tropic AAV capsids, cardiac- >1B specific promoters and regulatory elements screened to identify components that meaningfully out-perform existing options >50 In-house in vivo and in vitro models
Slide 46: Capsid engineering and manufacturing know-how building on AAV's success
Tenaya’s capsid engineering and manufacturing know-how are building on AAV’s success Capsid engineering efforts resulting in novel capsids with improved heart:liver tropism Cardiac-specific promoters and regulatory elements enable robust expression of target gene in the heart AAV manufacturing proce
Slide 47: Next generation AAV capsid engineering efforts
Next generation AAV capsid engineering efforts aimed at enhanced efficacy and safety Focused AAV Novel AAV Capsids for Heart that Outperform Parental Vectors Screening Efforts Using Multiple Strategies 2nd generation novel capsids demonstrate Top novel capsids show improved reduced trafficking to th
Slide 48: 2025 Milestones
yA TENAYA THERAPEUTICS 2025 Milestones
Slide 49: Anticipated 2025 milestones
Anticipated 2025 milestones 1H’25 2H’25 2026+ TN-201 • 1H’26: Present two-year Cohort 1 Present additional Cohort 1 • Provide Cohort 1 data and one-year Cohort 2 data MyPEAK-1 data update & present initial • Pursue regulatory alignment on • Complete Cohort 2 enrollment Cohort 2 data pivotal studie
Slide 50: Thank you
Thank you TENAYA THERAPEUT
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