Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — American Society of Gene & Cell Therapy (ASGCT) 2018
34 slides from Rocket Pharmaceuticals's conference presentation, May 18, 2018
Slide 1: American Society of Gene & Cell Therapy
American Society of Gene & Cell TherapyMay 18, 2018 Gaurav Shah, M.D.Chief Executive Officer and President
Slide 2: Important Information: Cautionary Statement Regarding Forward-Looking Statements
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 3: Developing best-in-class gene and cell therapies
Developing best-in-class gene and cell therapies for patients with devastating diseases. Inspired by transformative innovation, built on a sustainable and integrated multi-platform approach.
Slide 4: About Rocket Pharma
About Rocket Pharma Multi-Platform Gene Therapy (GTx) Company Targeting Rare Diseases1st-in-class with direct on-target mechanism of action (MOA) and clear clinical endpoints Ex-vivo Lentiviral vectors Fanconi Anemia (FA) Leukocyte Adhesion Deficiency-I (LAD-I) Pyruvate Kinase Deficiency (PKD)Infant
Slide 5: Pipeline-at-a-Glance
Therapies Discovery Preclinical Clinical Commercial Fanconi Anemia (FA) Leukocyte Adhesion Deficiency-I (LAD-I) Pyruvate Kinase Deficiency (PKD) Infantile Malignant Osteopetrosis (IMO) Undisclosed AAV CRISPR/Cas9 for FA Pipeline-at-a-Glance
Slide 6: Leveraging the Full Spectrum of GTx Platforms
In VivoAAV Gene Therapy Ex VivoLentiviral Gene Therapy Remove cells &isolate patient HSCs Laboratory- produced LV Laboratory- produced AAV Direct intravenous injection Gene-modifyHSCs Infusion of modified HSCs TherapeuticLVV TherapeuticAAV Leveraging the Full Spectrum of GTx Platforms
Slide 7: Fanconi Anemia (FA)
Fanconi Anemia (FA) Background:Etiology: FANC-A gene mutation → impaired DNA repairPathology: Bone marrow failure by age 10. Increased cancer risk of 30-50 fold (Acute Myeloid Leukemia and Head and Neck most common) 1Current available treatment: HSCT, associated w/ GVHDPrevalence: ~2,000 in US/EU~75
Slide 8: Rationale for Gene Therapy in FA: Somatic Mosaicism
Rationale for Gene Therapy in FA: Somatic Mosaicism = “Natural” GTx Somatic mosaicism in FA leads to stabilization/correction of blood counts, in some cases for decades. This uncommon variant results from a reverse mutation and demonstrates that a modest number of gene-corrected hematopoietic stem c
Slide 9: Gene Therapy Value Proposition: Early, Low-toxicity Intervention
Gene Therapy Value Proposition: Early, Low-toxicity Intervention to Prevent Hematologic Failure Gene therapy in FA: Potential to correct blood & bone marrow defect without conditioningNo/limited hospitalization or transplant-unit medical care required No anticipated further increase in risk of head
Slide 10: Updated Data from Phase 1/2 Gene Therapy Trial of RP-L102 in FA
Updated Data from Phase 1/2 Gene Therapy Trial of RP-L102 in Patients with Fanconi Anemia Key efficacy measurements:Genetic correction of bone marrow cells (engraftment): measured by peripheral blood VCNFunctional and phenotypic correction of bone marrow cells: measured by resistance to mitomycin-C
Slide 11: Results from Phase 1/2 Gene Therapy Trial of RP-L102 in Fanconi Anemia
Results from Phase 1/2 Gene Therapy Trial of RP-L102 in Patients with Fanconi Anemia Results:Genetic correction of bone marrow cells (engraftment): Post-treatment peripheral blood VCN increases in all patients. Patient 02002 (first patient with higher RP-L102 dose)17% at 12 months34% at 19 months44%
Slide 12: Bone Marrow Engraftment: Increasing Levels Confirm Survival Advantage
Bone Marrow Engraftment: Increasing Levels Confirm Survival Advantage of Gene-Corrected FA Cells Ciemat Data Presented at ASGCT May 2018 First Demonstration of Engraftment Without Conditioning (in contrast to Beta-thal, SCD, etc) 02002 (Cryo) (1.7x104 cCFU/Kg) 02004 (Cryo)(6.9x103 cCFU/Kg) 02006 (Fr
Slide 13: Functional Correction of Bone Marrow
Functional Correction of Bone Marrow MMC assay identifies cells resistant to Mitomycin-C (MMC), a standard DNA damaging agent Ciemat Data Presented at ASGCT May 2018 Progressive Phenotypic Correction of BM Cells (MMC-Resistance)
Slide 14: Gene Correction of Bone Marrow Stem Cells Across Multiple Lineages
Gene Correction of Bone Marrow Stem Cells: Observed Across Multiple Cell Lineages Peripheral Blood Bone Marrow Ciemat Data Presented at ASGCT May 2018
Slide 15: Safety: Lentiviral Integration Profile
Safety: Lentiviral Integration Profile Demonstrates Preferential Integration Away from Potentially Oncogenic Transcription Start Sites Ciemat Data Presented at ASGCT May 2018 0 2 4 6 8 10 10-5 kb 5-0 kb 0-10 10-20 20-30 30-40 40-50 50-60 60-70 70-80 80-90 90-100 TSS % in Gene Upstream % Integration
Slide 16: Gene Therapy Confers a Phenotype Similar to Somatic Mosaicism
Gene Therapy Confers a Phenotype Similar to Somatic Mosaicism DEB chromosomal assay measures Diepoxybutane (DEB)- induced chromosome breakage which is elevated in FA Ciemat Data Presented at ASGCT May 2018 Healthy Donor Mosaic FA Non-reverted FA Healthy Donor Mosaic FA Non-reverted FA Healthy Donor
Slide 17: Increases of Corrected vs Non-Corrected Leukocytes
Increases of Corrected vs- Non-Corrected Leukocytes Support Potential of Gene Therapy to Restore Normal Bone Marrow Function Uncorrected leukocytes/µL Corrected leukocytes/µL Ciemat Data Presented at ASGCT May 2018
Slide 18: Gene Therapy Stabilizes Markedly Declining Blood Counts
Gene Therapy Stabilizes Markedly Declining Blood Counts Months after gene therapy Months after gene therapy Months after gene therapy 02002 (Cryo) (1.7x104 cCFU/Kg)(2.5x105 cCD34+/Kg) 02004 (Cryo)(6.9x103 cCFU/Kg)(1.7x105 cCD34+/Kg) 02006 (Fresh)(1.6x105 cCFU/Kg)(4.0x105 cCD34+/Kg) 02005 (Fresh)(2.8
Slide 19: FA: Clinical Summary & Path Forward
FA: Clinical Summary & Path Forward
Slide 20: Leukocyte Adhesion Deficiency-I (LAD-I)
Leukocyte Adhesion Deficiency-I (LAD-I) Background:ITGB2 gene mutation → impaired CD18 expression & WBC migration → severe infections~50% patients w/severe variant → ~2/3 mortality by age 2Current available treatment: HSCT, associated with GVHDGTx potential market est. >25-50 patients/year Upcoming
Slide 21: Rationale for Gene Therapy in LAD-I: CD18 Expression and Survival
Rationale for Gene Therapy in LAD-I: CD18 Expression Correlative to Patient Survival The grey diamond indicates the 39% survival to age 2 years for 66 evaluable patients with severe LAD-I not receiving HSCT Poster Presentation at ASGCT May 2018 Natural history studies show the correlation between hi
Slide 22: 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 promotersMyeloablative conditioning was usedRocket chose the Chimeric cFES/CTSG (myeloid-specific ) promoter (Post-transplant PB VCN 0.4-0.9) 1o 2o Leon-Rico D, Aldea M, Sanch
Slide 23: LAD-I: Improved Process Produces VCN >2.4
LAD-I: Improved Process Produces VCN >2.4 Source: Company data on file VCN in Liquid Culture No Transduction Enhancers With Combination of Transduction Enhancers Improved Process Old Process VCN/cell Utilizing GMP vector branch
Slide 24: LAD-I Program Summary
LAD-I Program Summary Ultra-rare Disease = Streamlined Regulatory Approach Potential design & endpoints for approval Target Patient Population: Severe LAD-I patients (CD18<2%), ~2/3 mortality by 2yControl: Lit review of ~300 pts. (Rocket published*)Potential approval path: Early Endpoint Read: Modes
Slide 25: Pyruvate Kinase Deficiency (PKD)
Pyruvate Kinase Deficiency (PKD) Background:PKLR gene mutation → shortage of RBC ATP → hemolytic anemiaCurrent available treatment: transfusions, splenectomyGTx potential market est. >250 patients/year Upcoming Milestones:Rolling IMPD filing planned in early 2019 FA LAD-I PKD IMO AAV
Slide 26: 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 progressVCN now 2-4 range with TDx EnhancersGMP vector production slated to begin 201
Slide 27: Infantile Malignant Osteopetrosis (IMO)
Infantile Malignant Osteopetrosis (IMO) Background:TCIRG1 gene mutation → dysfunctional osteoclastsBone marrow failure, skeletal deformities, frequent mortality by age 10Current available treatment: HSCTGTx potential market est. >50 patients/year Upcoming Milestones:Clinical trials scheduled to begi
Slide 28: AAV Program (Undisclosed)
AAV Program (Undisclosed) Background:Monogenic multi-organ disease, death in teens without organ TxVector with on-target MOA, tissue specific tropismCurrent available treatment: Organ TxPrevalence US/EU: 15,000 to 30,000Upcoming Milestones:Preclinical data and disclosure of indication in 2H18Target
Slide 29: AAV: Activity in Mouse Model
AAV: Activity in Mouse Model Wild-type KO + AAV.EGFP KO + AAV.transgene Undisclosed collaborator data on file
Slide 30: AAV: Expression of Missing Protein in KO mice
AAV: Expression of Missing Protein in KO mice 3.532.521.510.50 WT KO GTx Mid GTx High GTx Low Undisclosed AAV GTx/GAPDH Ratio Undisclosed collaborator data on file
Slide 31: 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 programsOne pending PCT application for undisclosed AAV-b
Slide 32: World-Class Research and Manufacturing Partners
World-Class Research and Manufacturing Partners CIBEREl CIEMATFred Hutchinson Cancer Research CenterIIS FJDLund UniversityMemorial Sloan Kettering Cancer CenterMolMed S.p.A.Stanford Medical School
Slide 33: Leadership Team
Gaurav Shah, M.D.President & Chief Executive Officer Jonathan Schwartz, M.D.Chief Medical Officer & Head of Clinical Development Kinnari Patel, Pharm.D., MBAChief Operating Officer & Head of Development Led multiple biologics approvals Spearheaded Kymriah (CART-19) development at Novartis towards ap
Slide 34: Near-Term Potential Clinical Value Drivers
AAV: First disclosure of indicationLAD-I: Target IMPD filing Up to Four Programs in the ClinicClinical Data expected in up to Two Programs Near-Term Potential Clinical Value Drivers FA: Updated Patient Data Presented at ASGCT
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