Rocket Pharmaceuticals, Inc. · NASDAQ:RCKT
Rocket Pharmaceuticals — Investor Presentation (November 2018)
41 slides from Rocket Pharmaceuticals's investor presentation, Nov 26, 2018
Slide 1: Rocket Pharma November 2018
Slide 2: Important Information
Important Information rocket Dharma Cautionary Statement Regarding Forward-Looking Statements 8 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 produ
Slide 3: About Rocket Pharma
About Rocket Pharma roc k et Multi-Platform Gene Therapy (GTx) Company Targeting Rare Diseases -class with direct on-target mechanism of action (MOA) and clear clinical endpoints Excvivo Lentivial vectors + Fanconi Anemia (FA) + Leukocyte Adhesion Deficiency-1 (LAD-!) + Pyruvate Kinase Deficiency (P
Slide 4: Leadership Team - Expertise in GTx & Rare Diseases Clinical Development
Leadership Team - Expertise in GTx & Rare Diseases Clinical Development ‘Jonathan Schwartz, M.D. Chief Medical Officer & Head of Clinical Development Mount Sinai tmcln Sytame Led multiple biologics approvals Raj Prabhakar, MBA Claudine Prowse, Ph.D. Gaurav Shah, M.D. President & Chief Executive Offi
Slide 5: Rocket's Expanding Pipeline: Potential for Significant Value Creation Near and Long Term
Rocket's Expanding Pipeline: Potential for Significant Value Creation Near and Long Term roc ket harm Discovery Preclinical Clinical ‘Commercial Za —— lw AAV 5
Slide 6: Leveraging the Full Spectrum of GTx Platforms
Leveraging the Full Spectrum of GTx Platforms rocket In Vivo Ex Vivo AAV Gene Therapy Lentiviral Gene Therapy | DOD Therapeutic \ lw Therapeutic TO Direct intravenous A \ Infusion of injection modified HSCs
Slide 7: Danon Disease
Danon Disease Monogenic Heart Failure Syndrome rocket pharma Background: * Disease Target © Monogenic multi-organ disorder with early mortality primarily due to heart failure © Highly penetrant and X-linked dominant © No effective therapies + RP-ASO1: Rocket’s First-In-Class Investigational Gene The
Slide 8: RP-A501: First Investigational Gene Therapy
RP-A501: First Investigational Gene Therapy Targeting a Monogenic Heart Failure Syndrome roc ket Most Patients Present with Hypertrophic Cardiomyopathy (HCM) + Unexplained left ventricular wall thickness and electrophysiological abnormalities * Disease onset during childhood and adolescence followed
Slide 9: Danon Disease: Newly Discovered with Growing Attention
Danon Disease: Newly Discovered with Growing Attention Recent Clinical and Scientific Progress Has Increased Disease Understanding... + 1981: Danon Disease first described* '* 2000: LAMP2 mutation identified® + 2011-2013: LAMP2 inclusion in HCM commercial gene panels? ied in literature* ..But Danon
Slide 10: Danon Disease Prevalence: ~15-30K in the US+EU
Danon Disease Prevalence: ~15-30K in the US+EU rocket pharma Hypertrophic Cardiomyopathy (HCM) @ USHCM Prevalence: 600K-1MM++ @ 1-4% of HCM patients consistently identified with LAMP2 mutationsin multiple studies with >1000 subjects evaluated? e Danon Disease Patients with HCM? © 85% of males 0° 30%
Slide 11: Danon Disease: Devastating Multisystemic Disorder with No Specific Treatments
Danon Disease: Devastating Multisystemic Disorder with No Specific Treatments roc ket pharma + 95% of patients have severe cardiomyopathy ©. Patients die from progressive heart failure © Males frequently die in their teens and females die in their thirties and forties + Other clinical manifestations
Slide 12: Danon Disease: An Impairment in Autophagy Caused by LAMP2B Mutations
Danon Disease: An Impairment in Autophagy Caused by LAMP2B Mutations rocket ‘Macroautophagy ( ue 7 a 7 A) = a) od Isolation Membrane Cytosolic Proteins Cad Sarereeneat ‘Autophagosome anon Disease Xelinked cardiac & skeletal myopathy 2
Slide 13: RP-A501 Restores Cardiac Function in KO Mice
RP-A501 Restores Cardiac Function in KO Mice rocket pharma Dose-Dependent Improvements in Systolic and Diastolic Function in LAMP2 KO Mice <dPlat max (mmg/s) 3 3 Cardiac Contractility a. re Impaired Heat Contactity Cardiac Relaxation Zam yore ato P20 : i Tas WT PBS* 1613 S013 te14 2014 AAVOLAMP2B WT
Slide 14: RP-A501 Shows Survival Benefit at Higher Doses
RP-A501 Shows Survival Benefit at Higher Doses survival (%) = LAMP2 KO *ANVS 2xi0™ vaikg (re8) = Law Ko +Aave 1x10" vgikg (n=8) [== LAP? KO +AAVO S10 wag 010 TAN? KO +AAVO 1x10 vahkg (0-9) == LAMP? KO +PBS (n=12) ‘AAV9.LAMP2B, or PBS Note: All mice were sacrificed at Month 10 14
Slide 15: RNA: RP-A501 Elicits Expression of hLAMP2B mRNA in Cardiac Tissue of KO Mice
RNA: RP-A501 Elicits Expression of hLAMP2B mRNA in Cardiac Tissue of KO Mice 233 Fold Change vs PBS (Normalized by GAPDH) o8ssss aca hLAMP2B mRNA* P<0.0001 Peo0te = t P=0.0012 wr PBS 1013 5e13 1¢14 ‘AAV9.LAMP2B LAMP2 KO *hLAMP28 = Human LAMP26 2014 15
Slide 16: Protein: RP-A501 Elicits Expression of LAMP2B Protein and Autophagic Flux in Heart
Protein: RP-A501 Elicits Expression of LAMP2B Protein and Autophagic Flux in Heart rocket pharma hLAMP2 Protein Expression L311 Protein Expression = reo gy tom 28 rer -L 2 + #3 : 23 ts fe eases Be Peao0t esa Eg 00 = 53 = =i ene nai ras 3 z * Bos xT Zo. = Zoe WT PES 1613 S013 1014 2014 WT POS 1613 S0
Slide 17: Structural: RP-A501 Reduces Autophagic Vacuoles in All Examined Organs
Structural: RP-A501 Reduces Autophagic Vacuoles in All Examined Organs be rocket TAMP2 KO pharma ‘AAVS.LAMP2B Wild Type KO Control 5e13 vglkg 1et4 valkg 2614 valkg Skeletal Muscle
Slide 18: Preclinical Efficacy Summary
Preclinical Efficacy Summary rocket pharma * RP-A501 Shows Phenotype Improvements: o Survival benefit at higher doses o Dose-dependent restoration of cardiac function o Improvement in liver enzymes * RP-A501 Reduces Autophagic Vacuoles in All Examined Organs: Heart, Liver, Skeletal Muscle * RP-AS01
Slide 19: No Toxicities Observed in Mouse and Monkey Models
No Toxicities Observed in Mouse and Monkey Models rocket pharma RP-A501 Preclinical Safety Profile: * No therapy-related deaths * No significant hematologic changes * No significant biochemical changes * No significant clinical chemistry changes * Mild and transient ALT elevation that self-resolved
Slide 20: RP-A501 Clinical Development Plans
RP-A501 Clinical Development Plans Socket pharma 2019 Q Phase 1 with clinical GMP AAV9 RP-ASO1 in patients with Danon disease Q Continue registry & patient education/identification Q Clinical retrospective database in progress 2020 Q Phase 2/Registrational Study for BLA/MAA submission seeking Accele
Slide 21: Fanconi Anemia (FA)
Fanconi Anemia (FA) Monogenic DNA-repair disorder roc k et pharma FA Bone Marrow Birth Defects Platelets Skin Discoloration FANCA Gene Developmental Issues fetal at ape RBCs Bone Marrow Failure by Age 10 ere ‘Acute Myeloid Leukemia |_ (1 risk mnie) WBC Head and Neck Cancer? J 30-50x) +Current availa
Slide 22: Rationale for Gene Therapy in FA: Somatic Mosaicism = "Natural" GTx
Rationale for Gene Therapy in FA: Somatic Mosaicism = “Natural” GTx rocket pharma 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 hemato
Slide 23: Gene Therapy Value Proposition: Early, Low-toxicity Intervention to Prevent Hematologic Failure
Gene Therapy Value Proposition: Early, Low-toxicity Intervention to Prevent Hematologic Failure rocket pharma Gene therapy in FA: + Potential to correct blood & bone marrow defect without conditioning + No/limited hospitalization or transplant-unit medical care required Blood Counts + No anticipated
Slide 24: Updated Data from Phase 1/2 Gene Therapy Trial of RP-L102 in Patients with Fanconi Anemia
Updated Data from Phase 1/2 Gene Therapy Trial of RP-L102 in Patients with Fanconi Anemia rocket pharma Key efficacy measurements: © Genetic correction of bone marrow cells ASGCT (engraftment): measured by peripheral Samar blood VCN 2018 . a 7 MAY 16-19 ¢ Functional and phenotypic correction of bone
Slide 25: Functional Correction of Bone Marrow
Functional Correction of Bone Marrow pharma Correction of BM Cells (MMC-Resistance] 400. o Y= 4.311%-0.728 = ° R092 g & 5 g 10 3 4 3 & Q Q 2 2 2 . = = 1 Months "0 61226 0612 06122 0 ° 0 10 2 30 «640 80 % Corrected CD34" cells Post-GT a6R FA.02002 FA.02004 © FAZ005._—_FA- 02006 MMC assay identifies c
Slide 26: Gene Therapy Confers a Phenotype Similar to Somatic Mosaicism
Gene Therapy Confers a Phenotype Similar to Somatic Mosaicism rocket Presence of DEB Improvement of Chromosomal Stabilt * 02008 02002 9% Non-Aberrant Cells i worted FA ‘Months post Gene Therapy 02005 i : % Non-Aberrant Cells Ciemat Data Presented at ESGCT Oct 2018 DEB chromosomal assay measures Diep
Slide 27: Bone Marrow Engraftment: Increasing Levels Provide Evidence of Potential Survival Advantage
Bone Marrow Engraftment: Increasing Levels Provide Evidence of Potential Survival Advantage of Gene- Corrected FA Cells 02002 (Cryo) (.7210%e0FUKa) (02006 (Fresh) (.6et0"ecFUKa) PVN: 045 40.0 Col Dose: 560K COS4+iKg ay oe ondreresetatne Sihettget domogreane pVCN: 0.53 Cot Dose: 1.9M COB6+ig 8 3 3 é
Slide 28: Increases of Corrected Leukocytes Support Restoration of Normal Bone Marrow Function
Increases of Corrected Leukocytes Support Restoration of Normal Bone Marrow Function Consistent with Mosaic Phenotype rocket Kinetics of Corrected and Uncorrected PB Leukocytes Prior to and After Gene Therapy FA-02002 FA-02006 FA-02005 FA-02008 Sess ae = Date eee S sees “ : y aot Zo i we y = ! é ar
Slide 29: Gene Therapy Stabilizes Markedly Declining Blood Counts
Gene Therapy Stabilizes Markedly Declining Blood Counts Most Encouraging Counts Where Engraftment is High (>50%)* roc k et pharma iz is Phieeaa * 02002 (Cryo) 3 LAK i. tae FS N WAM Bw oaone fresn) b ia wi Ba i! : 7 eNO a " 02005 (Fresh) 3 i Sioeeneny Penoecrun) Et i rm, j E i z ea04cye) Fa : i PW Tr
Slide 30: FA: Clinical Summary & Path Forward
FA: Clinical Summary & Path Forward rocket pharma ‘+ Interim data from patients under “Process A” (12-month follow up) showed: Process ‘* Durable engraftment for up to 30 months A ‘= Continued improvement in phenotypic markers MMCand DEB. ‘= Continued stabilization of previously-declining blood coun
Slide 31: Leukocyte Adhesion Deficiency-I (LAD-I)
Leukocyte Adhesion Deficiency-| (LAD-!) Monogenic immunodeficiency disease rocket pharma Background: + ITGB2 gene mutation (encodes the CD18 protein) > leads to impaired CD18 expression & WBC migration > severe and recurring infections that could be fatal + ~75% patients w/severe variant > ~2/3 mort
Slide 32: Rationale for Gene Therapy in LAD-I: CD18 Expression Correlative to Patient Survival
Rationale for Gene Therapyin LAD-I: CD18 Expression Correlative to Patient Survival rocket Kaplan-Meier Survival Estimates by Neutrophil CD18 Expression Patients with moderate LAD-I not receiving allogeneic HSCT- Natural history studies show the correlation _ between higher CD18 Bc expression andlon
Slide 33: LAD-I: Mouse Study Shows LAD-I Correction
LAD-I: Mouse Study Shows LAD-I Correction rocket pharma Primary and serially OE impt Wi, Arpt transplanted LAD mice HE 3mpt W), 3mpt underwent CD18 lenti GTx with different promoters Myeloablative 2 conditioning was used B 8 2 Rocket chose the Chimeric & cFES/CTSG (myeloid- specific ) promoter (Post
Slide 34: LAD-I: Improved Process Produces VCN >~2-4
LAD-I: Improved Process Produces VCN >~2-4 VCN in Liquid Culture No Transduction Enhancers Improved Process 4 3 With Combination of Transduction Enhancers 3 2 old Pr & rocess 1 0 10 20 50 100 10 20 50 100 MOI Utilizing GMP vector batch Source: Company data on file 34
Slide 35: LAD-I Program Summary
LAD-I Program Summary rocket Ultra-rare Disease = Streamlined Regulatory Approach Potential design & clinical endpoints ‘Target Patient Population: Severe LAD-I patients (CD18<2%), ~2/3 mortality by 2y Control: Lit review of ~300 pts. (Rocket published") Potential Clinical Endpoi expression, Surviva
Slide 36: Pyruvate Kinase Deficiency (PKD)
Pyruvate Kinase Deficiency (PKD) Monogenic red blood cell disorder rocket pharma Background: + Severely affects the pediatric population + PKLR gene mutation > shortage of RBC ATP > hemolytic anemia that can range in severity (mild to severe) PKD * Current available treatment include transfusions &
Slide 37: PKD Program Summary
PKD Program Summary rocket Product/Manufacturing Optimization Positive outlook for near term optimization PoC. O Target effective engraftment requirement < 50% D Optimization of vector manufacturing + transduction process CIVCN now 2-4'range with TDx Enhancers Clinical Efficacy/Registration Status R
Slide 38: Infantile Malignant Osteopetrosis (IMO)
Infantile Malignant Osteopetrosis (IMO) Monogenic bone resorption disorder roc k et pharma Background: + Resulting in increased bone density and impaired bone resorption + TCIRG1 gene mutation > dysfunctional osteoclasts + Bone marrow failure, skeletal deformities, neurologic abnormalities, frequent
Slide 39: Growing IP Portfolio
Growing IP Portfolio rocket 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): OFA GLAD aPKD + One pending PCT application: {A Danon (Licensed t
Slide 40: World-Class Research and Manufacturing Partners
World-Class Research and Manufacturing Partners + CIBER + EICIEMAT + Fred Hutchinson Cancer Research Center + tis FuD + Lund University + Memorial Sloan Kettering Cancer Center + MolMed S.p.A. + REGENEXBIO + Stanford Medical School + University of California, San Diego pharma oa FunoAOON jibe? DAE P
Slide 41: Near-Term Potential Clinical Value Drivers
Near-Term Potential Clinical Value Drivers 1H19 Danon: IND Clearance; FPI FA: FPI Phase 1/2 trial (IND cleared in Nov '18) FA: Additional Data from Patients ‘Treated under “Process A” LAD+I: FPI for registration-enabling Phase 1/2 trial (IND cleared in Nov ’18) PKD: IMPD/IND submission; FP! FA: data
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