Slide 1: Update from Phase 1 Trial of RP-A501 Gene Therapy Treatment for Danon Disease
Update from Phase 1 Trial of RP-A501 Gene Therapy Treatment for Danon DiseaseSeptember 30, 2022
Slide 2: Disclaimer
DISCLAIMER Various statements in this release concerning Rocket’s future expectations, plans and prospects, including without limitation, Rocket’s expectations regarding its guidance for 2022, the safety and effectiveness of RP-A501 for the potential treatment of Danon Disease, trends for RP-A501 sa
Slide 3: Danon Disease: Serious Condition with Unmet Medical Need
Danon Disease (DD): Serious Condition with Unmet Medical Need Standard of care: Heart transplant (HTx) Limitations: Considerable morbidity and mortality Only ~20% of patients receive HTx Not curative of extracardiac disease Therapeutic Challenges X-linked, dominant, monogenic disease Loss-of-functio
Slide 4: RP-A501: Prospect of Direct Benefit
RP-A501: Prospect of Direct Benefit Age (years) 5 10 15 20 25 30 Cardiac Pathophysiology Symptom onset Diagnosis Progression to end-stagecardiomyopathy (potential for heart transplant) Death Gene therapy(hypothesized optimal treatment interval) Stabilization or improvement Trajectory of cardiac path
Slide 5: Pathophysiology and Clinical Manifestations of Danon Disease
Pathophysiology and Clinical Manifestations of Danon Disease HCM DD, Danon disease; LAMP2B, lysosome-associated membrane protein 2B; VT, ventricular tachycardia. Adapted from Jones & Arnold. 2014. Hypertrophic Cardiomyopathy: Pathogenesis and Clinical Findings Pathophysiology Mechanism Patient impac
Slide 6: Phase 1 Study: Non-Randomized Open Label
Phase 1 Study: Non-Randomized Open Label Non-randomized open label study in male DD patients INCLUSION CRITERIA Male Confirmed LAMP-2B mutations Cardiac involvement confirmed by imaging or ECG NYHA Class II or III Able to walk >150 m unassisted during 6-minute walk test (6MWT) EXCLUSION CRITERIA Ant
Slide 7: RP-A501: Safety Monitoring of Phase 1 Patients
RP-A501: Safety Monitoring of Phase 1 Patients Pt Age Wt 1001a 17.5 52.5 1002 20.4 89.1 1005 18.3 91.8 Cohort 1: Low-dose adult Cohort 2: High-dose adult Cohort 3: Low-dose pediatric 1.1 x 1014 GC/kg 6.7 x 1013 GC/kg 6.7 x 1013 GC/kg RP-A501 Steroid (prednisone 1mg/kg) Tacrolimus Tacrolimus Rituxima
Slide 8: RP-A501 Was Generally Well Tolerated in Pediatric Cohort on Enhanced Immunomodulation
RP-A501 Was Generally Well Tolerated in Pediatric Cohorton Enhanced Immunomodulation Minimal complement activation No complement-related clinical or laboratory AEs All AEs were transient and reversible No treatment-related SAEs Steroid (prednisone 0.5 – 0.8mg/kg and tapered starting day 10) Sirolimu
Slide 9: Early Pediatric Data are Encouraging and Consistent with Adult Efficacy Data
Early Pediatric Data are Encouraging and Consistent with Adult Efficacy Data at Similar Timeframe Variable Baseline2 Most Recent Follow-up LAMP2 protein3 (%) 2.6 354 Troponin-I (ng/mL) 0.67 0.07 BNP (pg/mL) 297 113 KCCQ-overall scale 52 815 NYHA Class II I 6 months AGE AT INFUSION 11.7 ye
Slide 10: Early Pediatric LAMP2 Expression are Encouraging and Consistent with Adult Data
Early Pediatric LAMP2 Expression are Encouraging and Consistent with Adult Data LAMP2, lysosome associated membrane protein 2. IHC, immunohistochemistry. Cohort Patient ID Initial Biopsy Post Infusion Pediatric - Low Dose 1008 Month 3: 18.5%* 1009 Month 3: 34.7% Adult - Low Dose 1001 Month 2: 7.3% 1
Slide 11: LAMP2 Myocardial Protein Expression and Histologic Improvement in the Pediatric Cohort
LAMP2 Myocardial Protein Expression and Histologic Improvement in the Pediatric Cohort EMB, endomyocardial biopsy; H&E, hematoxylin & eosin stain; LAMP2, lysosome associated membrane protein 2. A501-008-1008 Endomyocardial Biopsy (EMB) Images LAMP2 protein expression assessed (relative to normal hum
Slide 12: Pediatric LAMP2 Protein and DNA Suggests Durable Expression
Pediatric LAMP2 Protein and DNA Suggests Durable Expression As Demonstrated in Adult Cohort *LAMP2 protein expression assessed (relative to normal human controls) by core lab in a blinded fashion of entire tissue sample; Percentages reflect estimated extent of LAMP2 staining: Grade 0=negative staini
Slide 13: Restored Autophagy Sustained Following RP-A501
n=1 15 n=6 n=3 n=3 n=2 10 5 0 Predose Month 6 Vacuole Area/Tissue Area (%) Month 12 Month 24 Month 36 Restored Autophagy Sustained Following RP-A501 M, month; X, data not assessed B. 1001 1002 1005 1006 1008 M12 M24 M36 M6 M12 M24 M24 M6 M12 M6 M6 25 0 -25 -50 -75 -100 Improvement Vacuole Area/Tissu
Slide 14: Sustained Improvement or Stabilization of Biomarkers of Myocardial Injury and Stress
Sustained Improvement or Stabilization of Biomarkers of Myocardial Injury and Stress Following RP-A501 Brain Natriuretic Peptide (BNP) 1001 1002 1005 1006 High Sensitivity Troponin I (hsTnI) 25 0 -25 -50 -75 -100 M18 M24 M30 M36 X X X M18 M24 M30 M12 M18 M30 M18 M24 M12 Improvement hsTroponin I % Ch
Slide 15: Sustained Improvement or Stabilization of LV Hypertrophy Following RP-A501
Sustained Improvement or Stabilization of LV HypertrophyFollowing RP-A501 LV, left ventricle; LVPWd, LV posterior wall end diastole; M, month; X, data not assessed LV hypertrophy is assessed via LV posterior wall at end diastole (LVPWd) and LV mass. LV Posterior Wall Thickness LV Mass M18 M24 M30 M3
Slide 16: Sustained Improvement or Stabilization of Functional Cardiac Status Following RP-A501
Sustained Improvement or Stabilization of Functional Cardiac StatusFollowing RP-A501 Cohort Patient ID Baseline Month 12 Most Recent Follow-up Time of Most Recent Follow-up Low Dose Adult 1001a II II II 36 months 1002 II III I 30 months 1005 II II I 30 months High Do
Slide 17: Summary of Results
Summary of Results PEDIATRIC COHORT ADULT COHORT Low-dose continues to be generally well tolerated at 2-3 years post-treatment Increased LAMP2B protein expression was associated with durable disease improvement or stabilization including clinical status (NYHA class, KCCQ), LV hypertrophy (LV wall th
Slide 18: Connecting Surrogate Endpoints to Functional Outcomes for Pivotal Study
Connecting Surrogate Endpoints to Functional Outcomes for Pivotal Study* Molecular Expression Cellular Structure Cardiac Structure and Function Cardiac Structure and Function Clinical Status Endomyocardial Bx: LAMP2 protein expression Endomyocardial Bx: Vacuolar area Serology: Troponin-I BNP Echo Pa
Slide 19: Summary of Results
Summary of Results Phase 1 enrollment and treatment are complete The enhanced immunomodulatory regimen was generally well tolerated and has mitigated adverse events in the pediatric cohort, who are currently 6 and 11 months post treatment The early LAMP2 expression data from the pediatric cohort are
Slide 20: Development Plan: Moving toward pivotal Phase 2 study
Development Plan Moving toward pivotal Phase 2 study PLANNED GLOBAL REGISTRATIONAL PHASE 2 STUDY Expanded natural history study End of Phase 1 regulatory meeting with FDA Initiate Phase 2 global pivotal study activities Initiate female study PLANNED Phase 1 treatment completed in males Orphan Drug,