Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (November 2017)
30 slides from Rocket Pharmaceuticals's investor presentation, November 2017
Slide 1: Bringing curative gene therapies to patients with rare, undertreated diseases
Bringing curative gene therapies to patients with rare, undertreated diseases November 2017
Slide 2: Important Information
Important Information IMPORTANT ADDITIONAL INFORMATION TO BE FILED WITH THE SEC This communication is being made in connection with the proposed merger transaction involving Inotek Pharmaceuticals Corporation (Inotek) and Rocket Pharmaceuticals, Ltd. (Rocket). In connection with the proposed transac
Slide 3: About Rocket Pharma
About Rocket Pharma Multi-Platform Gene Therapy (GTx) Company Targeting Rare Diseases Ex-vivo Lentiviral vectors • Fanconi Anemia (FA) • Leukocyte Adhesion Deficiency-I (LAD-I) • Pyruvate Kinase Deficiency (PKD) • Infantile Malignant Osteopetrosis (IMO) In-vivo AAV • Monogenic Multi-organ Disease Mu
Slide 4: Pipeline-at-a-Glance
Pipeline-at-a-Glance Therapies Discovery Preclinical Clinical Commercialization RP-L01 Phase 1 Fanconi Anemia (FA) RP-L02 Phase 1/2 Leukocyte Adhesion Deficiency-I (LAD-I) Pyruvate Kinase Deficiency (PKD) Infantile Malignant Osteopetrosis (IMO) Undisclosed AAV CRISPR/Cas9 for FA 4
Slide 5: Leveraging the Full Spectrum of GTx Platforms
Leveraging the Full Spectrum of GTx Platforms In Vivo Ex Vivo AAV Gene Therapy Lentiviral Gene Therapy Laboratory- Remove cells & Laboratory- produced AAV isolate patient HSCs produced LV Therapeutic Therapeutic LVV AAV Gene-modify HSCs Direct intravenous Infusion of injection modified HSCs 5
Slide 6: Fanconi Anemia (FA)
Fanconi Anemia (FA) FA Background: • FANC-A gene mutation → impaired DNA repair • Bone marrow failure by age 10, cancer LAD-I • Current available treatment: HSCT, associated w/ GVHD PKD • Prevalence US/EU: ~2,000 • GTx potential market est. >250 patients/year IMO Upcoming Milestones: • Clinical PoC/
Slide 7: FA: Rare Somatic Mosaicism = Natural GTx / Selective Advantage
FA: Rare Somatic Mosaicism = “Natural” GTx / Selective Advantage Somatic mosaicism in 10-15% of FA patients leads to stabilization/correction of blood counts, in some cases for decades. Also, it has been shown that a few gene-corrected hematopoietic stem cells can repopulate the system w/corrected (
Slide 8: Upward In Vivo VCN Trajectory in Absence of Conditioning Confirms Selective Advantage in FA
Upward In Vivo VCN Trajectory in Absence of Conditioning Confirms Selective Advantage in FA First Demonstration of Engraftment Without Conditioning (in contrast to Beta-thal, SCD, etc) 1.50E-02 0.015 02004 02004 (1.7x10 (1.7x10 5 cCD34+/Kg) 5 cCD34 +/Kg) VCN / Cell 1.00E-02 0.010 5.00E-03 0.005 0.00
Slide 9: Progressive Increase in Multilineage Blood and Bone Marrow Gene-corrected Progenitors in FA
Progressive Increase in Multilineage Blood and Bone Marrow Gene-corrected Progenitors in FA Bone Marrow 6 months 0.50 0,30 0.30 12 months 0.40 0,25 0.25 0,20 0.20 0.30 VCN / Cell 0,15 0.15 0.20 0,10 0.10 0.10 0,05 0.05 0.00 0,00 0 CD34 Erythr. Megak Prog Total BM subpopulations Ciemat Data Patient 2
Slide 10: Clonal Diversity in PB Cells Confirms Long-term Multi-Lineage Repopulation Potential
Clonal Diversity in PB Cells Confirms Long-term Multi-Lineage Repopulation Potential Clonal diversity Wei Wang and Manfred Schmidt Ciemat Data Patient 2002 as of Nov 2017 10
Slide 11: Functional Correction in Bone Marrow
Functional Correction in Bone Marrow Reversion of MMC-Hypersensitivity of BM CFCs 11
Slide 12: Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2002)
Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2002) • Black numbered *’s represent months post-GTx • At a certain threshold of VCN and cell dose, we can re- create a mosaic phenotype 8 • Patient 2002, % aberrant Before GT 15 cells decreased to levels 7 0.51 1.5 documented i
Slide 13: Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2006)
Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2006) No Fanconi • Patient 2006, who has Fanconi Mosaic received the best dose to 02006 date with follow up, is converting to mosaic status Breaks /Aberrant cell by month 6 • Conclusion: Increasing the dose accelerates the conve
Slide 14: Improving Counts in FA Patient Receiving Highest Potency Product to Date
Improving Counts in FA Patient Receiving Highest Potency Product to Date Patient 2006 Neutrophils Platelets Hb 14 6 140 ( x 1 0 0 0 / µ l) P la te le ts (x 1 0 0 0 /µ l) 5 13 120 (x1,000/µL) (x1,000/µL) 4 H b (g /d L ) (gr/dl) 3 N e u t r o p h i ls 12 1 .0 100 11 0 .5 80 0 .0 10 60 -4 -2 0 2 4 6 -4
Slide 15: FA: Clinical Summary & Path Forward
FA: Clinical Summary & Path Forward • Selective advantage in FA leads to engraftment Current & clinical efficacy with GTx even with non- optimized process* • 6-8 patients with optimized process expected to Upcoming demonstrate faster engraftment & ↑ counts by YE’18 • Goal is to achieve accelerated a
Slide 16: Leukocyte Adhesion Deficiency-I (LAD-I)
Leukocyte Adhesion Deficiency-I (LAD-I) FA Background: • ITGB2 gene mutation → impaired CD18 expression & WBC migration → severe infections LAD-I • ~50% patients w/severe variant → ~2/3 mortality by age 2 • Current available treatment: HSCT, associated with PKD GVHD • GTx potential market est. >25-5
Slide 17: LAD-I: Mouse Study Shows LAD-I Correction
LAD-I: Mouse Study Shows LAD-I Correction Primary and serially transplanted LAD mice underwent CD18 lenti GTx with different promoters Myeloablative conditioning was used Rocket chose the Chimeric CTSG (myeloid-specific ) promoter (Post-transplant PB VCN 0.4-0.9) 1o 2o 17
Slide 18: LAD-I: Improved Process Produces VCN >1
LAD-I: Improved Process Produces VCN >1* 2 Improved process 1.6 1.2 VCN #102 #102 0.8 #104 Old process #104 0.4 0 Transduction Of HD CD34+ Cells IV * Combinations of transduction enhancers demonstrate further doubling or more of VCN (not shown) 18
Slide 19: LAD-I Program Summary
LAD-I Program Summary Ultra-rare Status = Streamlined Regulatory Approach Likely design & endpoints for approval Target Patient Population: • Severe LAD patients (CD18<2%), ~2/3 mortality by age 2 Control: • Lit review of ~300 pts. (Rocket completed, to publish) Likely approval path: • N=6 to 10, ma
Slide 20: Pyruvate Kinase Deficiency (PKD)
Pyruvate Kinase Deficiency (PKD) FA Background: • PKLR gene mutation → shortage of RBC ATP → hemolytic anemia LAD-I • Current available treatment: transfusions, splenectomy • GTx potential market est. >250 patients/year PKD Upcoming Milestones: IMO • Clinical trials to begin in 2018 AAV 20
Slide 21: PKD Program Summary
PKD Program Summary Product/Manufacturing Optimization Positive outlook for near term optimization PoC • Expected effective engraftment requirement < 50% • Optimization of vector manufacturing + transduction process in progress • VCN now 2-4 range with TDx Enhancers • GMP vector production to begin
Slide 22: Infantile Malignant Osteopetrosis (IMO)
Infantile Malignant Osteopetrosis (IMO) FA Background: • TCIRG1 gene mutation → dysfunctional osteoclasts • Bone marrow failure, skeletal deformities, frequent LAD-I mortality by age 10 • Current available treatment: HSCT PKD • GTx potential market est. >50 patients/year Upcoming Milestones: IMO • C
Slide 23: AAV Program (Undisclosed)
AAV Program (Undisclosed) FA Background: • Monogenic multi-organ disease, death in teens without organ Tx LAD-I • Vector with on-target MOA, tissue specific tropism • Current available treatment: Organ Tx • Prevalence US/EU: 15,000 to 30,000 PKD Upcoming Milestones: IMO • IND in 2018 AAV 23
Slide 24: AAV: Activity in Mouse Model
AAV: Activity in Mouse Model Wild-type KO + AAV.EGFP KO + AAV.transgene 24
Slide 25: AAV: Expression of Missing Protein in KO mice
AAV: Expression of Missing Protein in KO mice Undisclosed AAV GTx/GAPDH Ratio 3.5 3 2.5 2 1.5 1 0.5 0 WT KO GTx Low GTx Mid GTx High 25
Slide 26: Growing IP Portfolio
Growing IP Portfolio 4 in-licensed patent families for GTx products and related tech Supporting current pipeline efforts • In-licensed three pending international patent applications filed under Patent Cooperation Treaty (PCT) for FA, PKD & LAD programs • One pending PCT application for undisclosed
Slide 27: World-class Research and Manufacturing Partners
World-class Research and Manufacturing Partners 27
Slide 28: Our Leaders, Advisors and Investors are Pioneers in GTx & Rare Diseases
Our Leaders, Advisors and Investors are Pioneers in GTx & Rare Diseases Leadership Scientific Advisors Gaurav Shah, M.D. Jonathan Schwartz, M.D. Juan Bueren, Ph.D. Hans-Peter Kiem, M.D. Chief Executive Officer Chief Medical Officer Fanconi & LAD Advisory Board Fanconi Advisory Board • Novartis Cell
Slide 29: Key Near-term Value Drivers: 2018
Key Near-term Value Drivers: 2018 • Additional patient and proof of concept data FA expected in 2018 • Adaptive Phase 1/2 expected to begin in 2018 LAD-I • Proof of concept data expected in 2018/19 • Adaptive Phase 1/2 expected to begin in 2018 PKD • Proof of concept data expected in 2018/19 • Filin
Slide 30: Our home at NYC's biotech hub, the Alexandria Center for Life Science
Our home at NYC’s biotech hub, the Alexandria Center for Life Science Contact: Address 430 East 29th Street Suite #1040 New York, NY 10016 Phone 646-440-9100 Fax 646-224-9585 patients@rocketpharma.com Email info@rocketpharma.com Investors@rocketpharma.com 30
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