Slide 1: ASH: Breakout Session
ASH: Breakout Session December 8, 2019 1
Slide 2: Q&A Panelists
Q&A Panelists Brian Beard, Ph.D.: AVP, Chemistry Manufacturing and Control, LVV & AAV, Rocket Pharmaceuticals Agnieszka Czechowicz M.D., Ph.D.: Assistant Professor of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine at the Stanford University School of Medicine (FA) Donald
Slide 3: Agenda
Agenda Opening Remarks and Introductions 1 • Claudine Prowse, PhD—SVP, Corporate Development & Strategy RP-L102: Fanconi Anemia—Gaurav Shah, MD 2 • Gaurav Shah, MD—Chief Executive Officer & President RP-L201: Leukocyte Adhesion Deficiency-I 3 • Don Kohn, MD—Principal Investigator & Gaurav Shah, MD—C
Slide 4: Important Information
Important Information Cautionary Statement Regarding Forward-Looking Statements Various statements in this release concerning Rocket’s future expectations, plans and prospects, including without limitation, Rocket’s expectations regarding the safety, effectiveness and timing of product candidates th
Slide 5: RP-L102: Fanconi Anemia
RP-L102: Fanconi Anemia 5
Slide 6: What is Fanconi Anemia (FA)?
What is Fanconi Anemia (FA)? • Background: Caused by mutations in FANC family of genes which are involved in DNA repair DNA double- Fanconi anemia complex B • FANCA mutations: 60-70% of cases strand break A C M DNA repaired F • Disruption of FA pathway permits accumulation of E L G interstrand cross
Slide 7: FANCOLEN-I: Proof of Concept in FA
FANCOLEN-I: Proof of Concept in FA FANCOLEN-I is a Phase 1/2 clinical trial initiated by our academic partners at CIEMAT in Spain to evaluate safety and efficacy of the infusion of autologous CD34+ cells transduced with a lentiviral vector consisting of a lentiviral vector carrying the FANCA gene –
Slide 8: Process A: Bone Marrow Engraftment
Process A: Bone Marrow Engraftment First Demonstration of Engraftment Without Conditioning (“Process A”—non-optimized—RP-L102) pVCN: Product VCN * 8 0 .0 0 .8 * c e lls 2 0 .0 0 .2 0 a r k e d ccells a r k e d cells C o p ie s p e r g e n o m e e lls Copies C o p ie s per Copies per genome 6 0 .0 0
Slide 9: Process A: Functional Correction of Bone Marrow
Process A: Functional Correction of Bone Marrow Progressive Phenotypic Correction of BM Cells (MMC-Resistance) Y = 0 .9 3 * X + 2 .6 3 100 R = 0 .8 3 M M C S u r v iv a l (% ) MMC Survival (%) 80 e s is ta n c e M C rResistance 60 10 40 M MMC 20 1 m o n t h s Post-GT P o s t-G T 0 6 12 24 36 0 6 12
Slide 10: Process A: Gene Therapy Stabilizes and Improves Previously Declining Blood Counts
Process A: Gene Therapy Stabilizes and Improves Previously Declining Blood Counts 300 300 4 14 14 N e u t r o p h i l s ( x 1 0 0 0 / l) 300 4 14 N e u t r o p h i l s ( x 1 0 0 0 / l) 4 N e u t r o p h i l s ( x 1 0 0 0 / l) P l a t e l e t s ( x 1 0 0 0 / l) P l a t e l e t s ( x 1 0 0 0 /
Slide 11: FA: Process A to Process B
FA: Process A Process B CIEMAT-Sponsored • Interim data (>12-month follow-up) showed durable FANCOLEN 1 Study engraftment, continued improvement in phenotypic markers and stabilization of previously-declining blood counts Process A • No conditioning required Optimization Rocket-Sponsored • Clinica
Slide 12: RP-L102 Process B (FA) Clinical Trial
RP-L102 “Process B” (FA) Clinical Trial RP-L102 Process B - U.S. Phase 1 Primary Outcomes Inclusion Criteria • To evaluate the safety of the infusion of investigational • FA complementation group A product RP-L102: autologous CD34+ enriched cells • Age 1-12 years transduced with LV carrying the FANC
Slide 13: RP-L102: Subject Characteristics & Drug Product Metrics
RP-L102: Subject Characteristics & Drug Product Metrics Subject Characteristics Subject 1001 1002 Subject 1001 1002 Age (y) Gender 5F 6F MCV (fL) 86.9 106.2 WBC (/µL) 4,000 4,600 BM34+ (/µL) 78 34 PMN (/µL) 1,280 1,340 FA mutation c.2606A>C, c.(? -1)(522+1 523-1) p.(Gln869Pro) del encompassing c.281
Slide 14: RP-L102: Favorable Benefit/Risk Profile
RP-L102: Favorable Benefit/Risk Profile Adverse Events—No adverse events were associated with RP-L102 Administration Treatment-emergent Adverse Events: Event Adverse Events Grade any 1 2 3 4 Drug product and Pyrexia 1 1 -- -- -- patients’ blood post- infusion (2d & 6m) Croup (infectious) 1 -- -- 1 -
Slide 15: RP-L102: Preliminary Clinical Data
RP-L102: Preliminary Clinical Data Vector Copy Number Bone Marrow MMC-resistance Preliminary qPCR results at 4 months post infusion L102-001-1001 (PBMC): 10 MMC Resistance % • Pt 1001: VCN ~0.01 (1% correction) 8 50 nM MMC Pt 1002: VCN ~0.01 (1% correction) 6 Bone marrow specimen for patient 1002 in
Slide 16: RP-L102: Preliminary Clinical Data Blood Counts
RP-L102: Preliminary Clinical Data Blood Counts: Before and 6-Months After Receiving Therapy 3 15 150 Neutrophils (x1000/L) Leukocytes (x1000/L) 15 Platelets (x1000/L) Hemoglobin (g/dL) Patient 1001 10 2 10 100 5 1 5 50 0 0 0 0 -12 -8 -4 00 2 4 6 -12 -8 -4 00 2 4 6 -12 -8 -4 00 2 4 6 -12 -8 -4 00
Slide 17: RP-L102: Conclusions—Drug Product
RP-L102: Conclusions—Drug Product Conclusion 1.1 Investigational product metrics show consistency with parameters comparable or favorable relative to earlier processes: • Liquid culture VCNs >2.0 and CFC VCNs ~1.0 • CFC resistance (10nM MMC) in 30-50% range • VCNs were 2-3 fold improved while CD34+
Slide 18: RP-L102: Conclusions—Clinical
RP-L102: Conclusions—Clinical Conclusion 1.2 At 6 months, both patients are clinically stable with early indicators of engraftment in the absence of conditioning: • Preliminary gene marking (VCN) in PB at 4 months (qPCR) • Increasing bone marrow MMC-resistance at 6 months • Blood counts stable (pote
Slide 19: RP-L201: Leukocyte Adhesion Deficiency-I
RP-L201: Leukocyte Adhesion Deficiency-I LAD is CIRM funded 19
Slide 20: What is Leukocyte Adhesion Deficiency-I (LAD-I)?
What is Leukocyte Adhesion Deficiency-I (LAD-I)? ß2 Integrin α ß2 CD18 CD11 Tissue infiltration Leukocyte Defective expression of ß2 integrin on leukocytes limits their extravasation to inflamed sites. • Background: In LAD-I, mutations in the common chain (CD18) of the beta2-integrin family prevent
Slide 21: Clinical Pathogenesis of LAD-I
Clinical Pathogenesis of LAD-I Kaplan-Meier Survival Estimates by Neutrophil CD18 Expression1 LAD-1 Disease Spectrum -Patients with moderate LAD-I not receiving allogeneic HSCT- Moderate: Severe: 2-30% <2% CD18+ PMN CD18+ PMN PMN = polymorphonuclear neutrophils LAD-1 Clinical Prognosis • Patients su
Slide 22: RP-L201 (LAD-I): Clinical Trial and Outcome Measures
RP-L201 (LAD-I): Clinical Trial and Outcome Measures1 Trial Design – Non-Randomized Phase 1/2 Study Enroll 9 patients globally across Phase 1/2 Phase 1: Enroll two patients to assess safety and tolerability (n=2) Phase 2: Overall survival at multiple sites (U.S. and EU) (n=7) Primary Outcomes Second
Slide 23: Medical History of Patient L-201-003-1001
Medical History of Patient L-201-003-1001 Hospitalized IV Abx, Steroids Hospitalized IV Abx, Transfusion IV Abx, Ustekinumab Hospitalized Multiple Abscesses Pyoderma Buttocks Suspected Nocardia Gangrenosum Pyoderma Enbrel, Abx Pneumonia Lower Back Gangrenosum Severe Anemia (BM Lower Bx site) Back (B
Slide 24: RP-L201: Visible Improvements Post-Treatment
RP-L201: Visible Improvements Post-Treatment Prior to Gene Therapy—At Baseline Post Gene Therapy—At 3-Months Spontaneous Abdominal Lower Back Lesion Spontaneous Abdominal Lower Back Lesion Lesion (after BM aspirate) Lesion (after BM aspirate) UCLA Mattel Children’s Hospital Data December 2019 24
Slide 25: RP-L201: Visible Improvements Post-Treatment
RP-L201: Visible Improvements Post-Treatment No Infection/Inflammation After 3-Month Bone Marrow Biopsy Prior to Gene Therapy: BM Bx Site BM Bx Site 2 Days After 3-Month Marrow Bx Lower Back Lesion Lower Back (after BM aspirate) (after BM aspirate) UCLA Mattel Children’s Hospital Data December 2019
Slide 26: RP-L201: Drug Product Metric and Clinical Results
RP-L201: Drug Product Metric and Clinical Results Key Drug Product Metrics Clinical Results • CD34+ Cell Dose: 4.2 x 106 cells/kg • VCN (myeloid) 3-months post-treatment: 1.5 • Drug Product VCN: 3.8 • CD18 Expression in Peripheral Blood: - 3-month CD18 expression post-treatment: 45% - Pre-treatment
Slide 27: LAD-I: New Patients Identified to Date
LAD-I: New Patients Identified to Date Geographic Age Gender Status Location 4 years F US Enrolled 2 years F US Meets eligibility criteria; awaiting enrollment 2 years F India Meets eligibility criteria; obtained visa to enter US; awaiting enrollment Flow cytometry consistent with severe LAD-I; pati
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Slide 29: Q&A Panelists
Q&A Panelists Brian Beard, Ph.D.: AVP, Chemistry Manufacturing and Control, LVV & AAV, Rocket Pharmaceuticals Agnieszka Czechowicz M.D., Ph.D.: Assistant Professor of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine at the Stanford University School of Medicine (FA) Donald