october 2019 important information

October 2019 Important Information Cautionary Statement Regarding - PowerPoint PPT Presentation

October 2019 Important Information Cautionary Statement Regarding Forward-Looking Statements Various statements in this release concerning Rockets future expectations, plans and prospects, including without limitation, Rockets expectations

  1. October 2019

  2. 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 that Rocket may develop, including in collaboration with academic partners, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon disease and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe", "expect", "anticipate", "intend", "plan", "will give", "estimate", "seek", "will", "may", "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s ability to successfully demonstrate the efficacy and safety of such products and pre- clinical studies and clinical trials, its gene therapy programs, the preclinical and clinical results for its product candidates, which may not support further development and marketing approval, the potential advantages of Rocket’s product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket’s and its licensors ability to obtain, maintain and protect its and their respective intellectual property, the timing, cost or other aspects of a potential commercial launch of Rocket’s product candidates, Rocket’s ability to manage operating expenses, Rocket’s ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled “Risk Factors” in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2018. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

  3. Gene Therapy: A Multi-Platform Approach In Vivo (In Body) Ex Vivo (Outside Body) AAV Gene Therapy Lentiviral Gene Therapy Laboratory- Remove cells & Laboratory- produced AAV isolate patient HSCs produced LV Therapeutic LVV Therapeutic AAV Gene-modify HSCs Direct intravenous Infusion of injection modified HSCs 3

  4. About Rocket Pharma Multi-Platform Gene Therapy (GTx) Company Targeting Rare Diseases 1 st -in-class with direct on-target mechanism of action (MOA) and clear clinical endpoints  Fanconi Anemia (FA) Ex-vivo Lentiviral vectors (LVV)  Leukocyte Adhesion Deficiency-I (LAD-I)  Pyruvate Kinase Deficiency (PKD)  Infantile Malignant Osteopetrosis (IMO)  Danon Disease In-vivo adeno-associated virus (AAV) Multiple Near- & Medium-term Company Value Drivers  Four programs in the clinic (FA, LAD-I, PKD, Danon) Near-term Milestones (2019)  Additional clinical data for FA and LAD-I  FA and LAD-I advance to potential registration trial stage  Registrational studies ongoing in four programs Medium-term Milestones (2020-2021)  Ongoing data from Danon, FA, LAD-I and PKD  First global submission (BLA/MAA)  Platform establishment and pipeline expansion  Currently planned programs eligible for Pediatric Priority Review Vouchers Strong Precedents and World-Class Expertise  Precedents for LVV- & AAV-based therapies Strong Precedents and Sound Strategy  Clearly-defined product metrics across indications  Experienced company leadership  Leading research and manufacturing partners 4

  5. Leadership Team: Expertise in GTx & Rare Diseases Clinical Development Gaurav Shah, M.D. President & Chief Executive Officer Jonathan Schwartz, M.D. Kinnari Patel, Pharm.D., MBA CMO & SVP, Clinical Development COO & EVP, Development Spearheaded Kymriah (CART-19) development Led Opdivo and six rare disease indication Led multiple biologics approvals at Novartis towards approval approvals Annahita Keravala, Gayatri R. Rao, M.D., Claudine Prowse, Christopher Ballas, Raj Prabhakar, MBA Brian C. Beard, Ph.D. J.D. Ph.D. Ph.D. SVP, Bus Operations & Ph.D. AVP, SVP, Strategy & VP, VP, Reg Policy & Patient Bus Development AVP, CMC AAV Platform Corporate Dev Manufacturing Advocacy Lenti & AAV 7-Year Former ~17 years cell, gene ~20 years capital ~20 years cell and gene Director of FDA’s 15+ years cell and gene 20+ years gene and biotech markets, strategy, therapy development & Office of Orphan therapies expertise therapy expertise business development corporate manufacturing Products Development development 5

  6. Rocket’s Expanding Pipeline: Potential for Significant Value Creation Near and Long Term Discovery Preclinical Phase 1 Phase 2 Designations Fast Track, Orphan RP-A501 Drug (U.S.) Danon Disease RMAT, ATMP, Fast Track, Rare Pediatric, RP-L102 Orphan Drug (U.S./EU) Fanconi Anemia ATMP, Fast Track, RP-L201 Rare Pediatric, Orphan Drug Leukocyte Adhesion (U.S./EU) Deficiency-I Orphan Drug RP-L301 (U.S./EU) Pyruvate Kinase Deficiency Rare Pediatric, RP-L401 Orphan Drug (U.S.) Infantile Malignant Osteopetrosis AAV LVV 6

  7. Danon Disease Monogenic Heart Failure Syndrome RP-A501 Overview: Danon Disease • Background: Devastating multisystemic disorder caused by highly penetrant and X-linked dominant LAMP2 mutations RP-L102 • Currently available treatments : Non-curative heart Fanconi Anemia transplants associated with considerable morbidity and mortality RP-L201 • Addressable Market: Estimated U.S.+EU prevalence of Leukocyte Adhesion Deficiency-I 15,000-30,000 RP-L301 • RP-A501 : AAV9 gene therapy product that elicits Pyruvate Kinase improvements in survival, cardiac function, and liver enzymes Deficiency in preclinical studies RP-L401 • Regulatory Designations : Orphan Drug & Fast Track Infantile Malignant designations in the U.S. Osteopetrosis 7

  8. Danon Disease: An Impairment in Autophagy Caused by LAMP2B Mutations 8

  9. RP-A501 Restores Cardiac Function in KO Mice Dose-Dependent Improvements in Systolic and Diastolic Function in LAMP2 KO Mice Cardiac Contractility Cardiac Relaxation 0 10000 dP/dt min (mmHg/s) P<0.0001 dP/dt max (mmHg/s) P<0.0001 8000 -2000 P<0.0001 P<0.0001 P=0.045 P=0.011 P=0.005 P=0.0093 P=0.0018 6000 P=0.005 -4000 4000 -6000 2000 -8000 0 * WT PBS 1e13 5e13 1e14 2e14 * WT PBS 1e13 5e13 1e14 2e14 AAV9.LAMP2B AAV9.LAMP2B LAMP2 KO LAMP2 KO Lower dP/dt max indicates impaired contractility; Higher (less negative) dP/dt min indicates impaired heart relaxation *PBS = Phosphate Buffered Saline (Negative Control) 9

  10. RP-A501 Shows Survival Benefit at Higher Doses Note: All mice were sacrificed at Month 10 10

  11. RNA: RP-A501 Elicits Expression of hLAMP2B mRNA in Cardiac Tissue of KO Mice hLAMP2B mRNA* *hLAMP2B = Human LAMP2B 11

  12. Protein: RP-A501 Elicits Durable Expression of LAMP2B Protein and Autophagic Flux in Heart 1 Western Blot LAMP2 Protein Expression LC3-II Protein Expression P = 0.0072 Mouse Human P = 0.019 LAMP2 LAMP2 (Normalized to GAPDH) 1.5 P = 0.033 (Normalized to GAPDH) 5 LC3-II Intensity LAMP2 Intensity 4 1.0 P = 0.0001 3 P = 0.0001 0.5 2 P = 0.002 1 0.0 0 Untx PBS 1e13 5e13 1e14 2e14 Untx PBS 1e13 5e13 1e14 2e14 AAV9.LAMP2B AAV9.LAMP2B WT LAMP2 KO WT LAMP2 KO 1 Data are Mean ± SEM. N=5-8 per group. Untx = Untreated, PBS = Phosphate buffered saline Note: Mouse LAMP2 and Human LAMP2 data are from separate Western blots. 12

  13. Structural: RP-A501 Reduces Autophagic Vacuoles in All Examined Organs LAMP2 KO AAV9.LAMP2B KO Control 5e13 vg/kg 1e14 vg/kg 2e14 vg/kg Wild Type Heart Liver Skeletal Muscle 13

  14. Dose-dependent Widespread LAMP2 Expression in Cardiac Tissue 14

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