bringing curative gene therapies to patients with rare ... curative gene therapies to patients with...

January 2018

Bringing curative gene therapies to patients with rare, undertreated diseases

Important InformationCautionary Statement Regarding Forward-Looking Statements Various statements in this presentation concerning Rocket Pharmaceuticals, Inc. (the Company) and the Companys future expectations, plans and prospects, including without limitation, the Companys expectations regarding the safety, effectiveness and timing of products that the Company may develop, including in collaboration with partners, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD) and Infantile Malignant Osteopetrosis (IMO), 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 L.C. 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 the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company 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, the Companys ability to successfully demonstrate the efficacy and safety of such products and pre-clinical studies and clinical trials, its gene therapy programs, the pre-clinical and clinical results for its product candidates, which may not support further development and marketing approval, the potential advantages of the Companys 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, the Companys 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 ofthe Companys product candidates, the Companys ability to manage operating expenses, the Companys ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, the Companys 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 the Definitive Proxy Statement on Schedule 14A filed by the Company with the Securities and Exchange Commission in connection with the merger of Rocket Pharmaceuticals, Ltd. with the Company. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. You should therefore not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation.

3

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) Infantile Malignant Osteopetrosis (IMO)

In-vivo AAV Monogenic Multi-organ Disease

Multiple Near- & Medium-term Company Value Drivers

Near-term Milestones (2018) Additional clinical data for FA over the next 12-18 months Disclosure of AAV program (3Q18) Additional programs advance towards the clinic (4Q18)

Medium-term Milestones (2019-2021) FA advances to pivotal trial stage (2019) Registration trials for currently planned programs; first BLA

submissions Platform establishment and pipeline expansion Currently planned programs eligible for Priority Review Vouchers

Strong Precedents and World-Class Expertise

Strong Precedents and Sound Strategy Precedents for lenti- & AAV-based therapies Clearly-defined product metrics across indications Experienced company leaders Leading research & manufacturing partners

4

Gaurav Shah, M.D.President & Chief Executive Officer

Program Head CART-19 Novartis

4

Jonathan Schwartz, M.D.Chief Medical Officer

Kinnari Patel, Pharm.D., MBAChief Operating Officer

Led multiple biologic approvals Led 7 rare disease indicationapprovals

Robert KutnerAVP Gene Therapy Innovation

Claudine Prowse, Ph.D.Head of Corporate

Development & IRO

Process development head Joins from ITEK/Rocket Merger

ManagementJuan Bueren, Ph.D.

Fanconi & LAD Advisory BoardHans-Peter Kiem, M.D.Fanconi Advisory Board

Grover Bagby, M.D.Fanconi Advisory Board

Adrian Thrasher, M.D., Ph.D.Fanconi & LAD Advisory Board

Jose Carlos Segovia, Ph.D.PKD Advisory Board

Donald Kohn, M.D., U.U.C, B.S., M.S.

LAD & IMO Advisory Board

Scientific Advisors

Our Leaders and Advisors are Pioneers in Gene Therapy & Rare Disease

5

Therapies Discovery Preclinical Clinical Commercialization

Fanconi Anemia (FA)

Leukocyte Adhesion Deficiency-I (LAD-I)

Pyruvate Kinase Deficiency (PKD)

Infantile Malignant Osteopetrosis (IMO)

Undisclosed AAV

CRISPR/Cas9 for FA

Hutch Phase 1 1

Ciemat Phase 1 2

Pipeline-at-a-Glance

1Conducted by Fred Hutchinson Cancer Canter (RP-L101); 2 Conducted by Ciemat (RP-L102); two separate in-licensed product candidates each with its own lentiviral vector

6

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

TherapeuticLVVTherapeutic

AAV

Leveraging the Full Spectrum of GTx Platforms

7

Fanconi Anemia (FA)

Background: FANC-A gene mutation impaired DNA repair Bone marrow failure by age 10, cancer Current available treatment: HSCT, associated w/ GVHD Prevalence US/EU: ~2,000 ~75-80 transplants/yr in US/EU 1

~30-40% of pts receive transplant 2

GTx potential market est. >250 patients/year

Upcoming Milestones: Additional clinical data over the next 12-18 months Advance to pivotal trial stage in 2019

FA

LAD-I

PKD

IMO

AAV

1 CIBMTR and EBMT registries 2009-2013; 2 Alter BP et al. Haematologica 2017

8

FA: Rare Somatic Mosaicism = Natural GTx / Selective Advantage

Somatic mosaicism in up to 15% of FA patients1 leads to stabilization/correction of blood counts, in some cases for decades. We believe this demonstrates that a modest number of gene-corrected hematopoietic stem cells can repopulate a patients blood and bone marrow w/corrected (non-FA) cells. 2

86 106 126 146 166 186 206 226 246 266

Rela

tive

Valu

e (%

)

120

100

80

60

40

20

1

Neutros VCM HbPlat

1 Soullier, J., et al. (2005) Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway.Blood 105: 1329-1336; 2Data on file: Showing a single patient with a spontaneous correction of blood counts, no therapy administered

Months

Perc

ent N

orm

al

9

Upward In Vivo VCN Trajectory in Absence of Conditioning Confirms Selective Advantage in FA (Patients 02002 through 02006)

Ciemat Data Presented at ESGCT October 2017

First Demonstration of Engraftment Without Conditioning (in contrast to Beta-thal, SCD, etc)

Months post-infusion

02004(1.7x105 cCD34+/Kg)

0.00E+00

5.00E-03

1.00E-02

1.50E-02

0.5 1 1.5 2 4 6 9 120.5 1 1.5 2 4 6 9 12

0.015

0.010

0.000

0.005VC

N /

Cel

l

02004

02005 02002

02006

10

Progressive Increase in Multilineage Blood and Bone Marrow Gene-corrected Progenitors in FA (Patient 2002)

0,00

0,05

0,10

0,15

0,20

0,25

0,30

CD34 Erythr.Prog

Megak

Total BM subpopulations

VCN

/ Cel

l

Bone Marrow 6 months12 months

0

0.05

0.10

0.15

0.20

0.25

0.30

0.00

0.10

0.20

0.30

0.40

0.50


Grfico1

0.1030.1642704256

0.08360906740.2649141566

00.2268310573

0.1119050280.2514988481

6 months

12 months

VCN / Cell

Bone Marrow

FA-02005 MO

subpopulations

VCN FA-02005BM aspirationtotal BMMegakaryocytesCD34Erythroid Progenitors

BM 6 mesescresta izquierda0.007060.85350.01220.0415

cresta derecha0.00319ND0.0532ND

Grey: Psi value is below 100 molecules CT> 32, estndar plasmid curve point 102: 31,77 and 33,3 (22.07.16)

Rio Galdo, Paula:qPCR 22.07.16

Rio Galdo, Paula:Resultados qPCR 22.07.16

FA-02005 SP

VCN FA-02005SPsubpopulationssubpopulations

CD14CD15CD3CD19VCN FA-02005BM aspirationtotal BMMegakaryocytesCD34Erythroid Progenitors

2 Semanas0.000590.1530.0890.140BM 6 mesescresta izquierda0.007060.85350.01220.0415

4 Semanas0.000231.45283.71680.58610.7559cresta derecha0.00319ND0.0532ND

6 Semanas0.000401.33240.1555ND0.0809

2 meses0.000180.01800.04690.0000ND

3 meses0.00229

4 meses0.000300.18430.00130.01180.0000

6 meses0.00275849920.00614969250.00566856850.00251861540.0064811668

Grey: Psi value is below 100 molecules CT> 32, estndar plasmid curve point 102: 31,77

Rio Galdo, Paula:resultados del 18.04.16






FA-02002 SP y MO

VCN FA-02002total PBsubpopulationsVCN FA-02002Total BMsubpopulations

CD14CD15CD3CD19CD34Erythr. ProgMegak

2 Semanas0.0000NDND0.00120.0035

4 Semanas0.0023NDNDND0.0456

6 Semanas0.00120.22580.00400.00020.0041

2 months0.0007ND0.00870.00010.0006

4 months0.02160.34270.31570.05490.0287

6 months0.06540.15960.0882ND0.06106 months0.10300.0836ND0.1119

9 months0.13780.27770.17910.00040.1638

12 months0.16640.29040.20430.00570.207412 months0.16430.26490.22680.2515

15 months0.22240.15350.10770.04900.2447

19 months0.34440.45210.41640.16470.3803



FA-02002 SP y MO

total PB

CD14

CD15

CD3

CD19

VCN

FANCOLEN 02002 PB subpopulations

FA-02006 SP y MO

VCN FA-02006SPsubpopulationsVCN FA-02006Total BMsubpopulations


2 Semanas0.00114

4 Semanas0.00105

6 Semanas0.00317

2 mesesNA0.002860.000165

4 meses0.00684

6 meses0.0245NDND0.00270.00916 months0.03680.0481NDND

12 months

Total BM

CD34

Erythr. Prog

Megak

VCN

FANCOLEN 02002: BM subpopulations (6 and 9 months post GT)

6 months

9 months

12 months

15 months

19 months

VCN

Gene-marked subpopulations (PB)

6 months

12 months

VCN

Gene-marked subpopulations (BM)


Hoja2

Hoja3

Grfico1

0.06542727090.13778131680.16639551570.22236564290.3443850519

0.15961241490.2777314420.29042663230.15352828770.4521066366

0.08818413870.17910150310.20430787610.10770369840.4163919528

00.00039731710.00572741310.04902715210.1646998463

0.06101708950.16379041030.2074367620.24473413080.3803447717

6 months

9 months

12 months

15 months

19 months

VCN / Cell

Peripheral Blood

FA-02005 MO

subpopulations

VCN FA-02005BM aspirationtotal BMMegakaryocytesCD34Erythroid Progenitors

BM 6 mesescresta izquierda0.007060.85350.01220.0415

cresta derecha0.00319ND0.0532ND

Grey: Psi value is below 100 molecules CT> 32, estndar plasmid curve point 102: 31,77 and 33,3 (22.07.16)



FA-02005 SP

VCN FA-02005SPsubpopulationssubpopulations

CD14CD15CD3CD19VCN FA-02005BM aspirationtotal BMMegakaryocytesCD34Erythroid Progenitors

2 Semanas0.000590.1530.0890.140BM 6 mesescresta izquierda0.007060.85350.01220.0415

4 Semanas0.000231.45283.71680.58610.7559cresta derecha0.00319ND0.0532ND

6 Semanas0.000401.33240.1555ND0.0809

2 meses0.000180.01800.04690.0000ND

3 meses0.00229

4 meses0.000300.18430.00130.01180.0000

6 meses0.00275849920.00614969250.00566856850.00251861540.0064811668








FA-02002 SP y MO

VCN FA-02002total PBsubpopulationsVCN FA-02002Total BMsubpopulations


2 Semanas0.0000NDND0.00120.0035

4 Semanas0.0023NDNDND0.0456

6 Semanas0.00120.22580.00400.00020.0041

2 months0.0007ND0.00870.00010.0006

4 months0.02160.34270.31570.05490.0287

6 months0.06540.15960.0882ND0.06106 months0.10300.0836ND0.1119

9 months0.13780.27770.17910.00040.1638

12 months0.16640.29040.20430.00570.207412 months0.16430.26490.22680.2515

15 months0.22240.15350.10770.04900.2447

19 months0.34440.45210.41640.16470.3803



FA-02002 SP y MO

total PB

CD14

CD15

CD3

CD19

VCN

FANCOLEN 02002 PB subpopulations

FA-02006 SP y MO

VCN FA-02006SPsubpopulationsVCN FA-02006Total BMsubpopulations


2 Semanas0.00114

4 Semanas0.00105

6 Semanas0.00317

2 mesesNA0.002860.000165

4 meses0.00684

6 meses0.0245NDND0.00270.00916 months0.03680.0481NDND

12 months

Total BM

CD34

Erythr. Prog

Megak

VCN

FANCOLEN 02002: BM subpopulations (6 and 9 months post GT)

6 months

9 months

12 months

15 months

19 months

VCN

Gene-marked subpopulations (PB)

6 months

12 months

VCN

Gene-marked subpopulations (BM)


Hoja2

Hoja3

11

Functional Correction in Bone MarrowReversion of MMC-Hypersensitivity of BM CFCs

MMC= Chromosome Assay for FA. Identifies resistant cells to Mitomycin C, (MMC), a common cross-linking agent


12

Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2002)

Before GT

0.51 1.54

212

815

7

Black numbered *s represent months post-GTx

At a certain threshold of VCN and cell dose, we can re-create a mosaic phenotype

Patient 2002, % aberrant cells decreased to levels documented in mosaic patients at 15 months post gene therapy

DEB= Chromosome Assay for FA.Measures Diepoxybutane (DEB)- induced chromosome breakage which is elevated in FA

Castella M, Pujol R, Calln E, et al. Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact. J Med Genet 2011 48: 242-250. doi: 0.1136/jmg.2010.084210; Ciemat Data for patient 2002 Presented at ESGCT October 2017

13

Reversion of DEB-induced Chromosomal Instability in PB T Cells (Patient 2006)

00.5

1 1.5

46

No FanconiFanconiMosaic02006

% Aberrant cells

Bre

aks

/Abe

rran

t cel

l

Patient 2006, who has received the best dose to date with follow up, is converting to mosaic status by month 6

Conclusion: We believe increasing the dose accelerates the conversion of patients to mosaic status

DEB= Chromosome Assay for FA.Measures Diepoxybutane (DEB)- induced chromosome breakage which is elevated in FA

Castella M, Pujol R, Calln E, et al. Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact. J Med Genet 2011 48: 242-250. doi: 0.1136/jmg.2010.084210; Ciemat Data for patient 2006 Presented at ESGCT October 2017

14

Stable to Improving Counts in FA Patient Receiving Highest Potency Product to Date

m o n t h s p o s t g e n e t h e r a p y

Hb

(g

/dL

)

- 4 - 2 0 2 4 6

1 0

1 1

1 2

1 3

1 4

(gr/d

l)


Pla

tele

ts (

x1

00

0/

l)

- 4 - 2 0 2 4 6

6 0

8 0

1 0 0

1 2 0

1 4 0

(x1,

000/

L)

Patient 2006

Months preceding or following gene therapy treatment

Hb Neutrophils Platelets

GTx GTx GTx

- 4 - 2 0 2 4 6

0 . 0

0 . 5

1 . 0

3

4

5

6


Ne

ut

ro

ph

ils

(x

10

00

/l)

(x1,

000/

L)


15

Potential Advantages of GTx over Transplant for FABl

ood

Coun

ts

Age

DVCV

Transplant

GTx

Expected Advantages of GTx : Corrects blood & bone

marrow defect without conditioning

No hospitalization or transplant-unit medical care required

No further increase in risk of head and neck cancer

GTx implemented as preventative measure to avert bone marrow failure; BMT is indicated once marrow failure has occurred

16

FA: Clinical Summary & Path Forward

Selective advantage in FA leads to engraftment & evidence of potential efficacy with GTx even with non-optimized process*

Current

Additional patients with optimized process may demonstrate faster engraftment & counts by YE18Upcoming

Goal is to achieve accelerated approval and incorporate GTx for FA early in life as preventative for BM failureRegulatory

*Of the four patients treated to date and who have been followed 6 months (in the Ciemat Phase 1 trial), all four have stable or improving blood counts despite in months & years prior to GTx, despite a non-optimized process.

17

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 2 Current available treatment: HSCT, associated with

GVHD GTx potential market est. >25-50 patients/year

Upcoming Milestones: File IMPD in Spain in 4Q18

FA

LAD-I

PKD

IMO

AAV

18

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 2oLeon-Rico D, Aldea M, Sanchez-Baltasar R, Mesa-Nuez C, Record J, Burns SO, Santilli G, Thrasher AJ, Bueren JA, Almarza E. Hum Gene Ther. 2016 Sep;27(9):668-78. doi: 10.1089/hum.2016.016. Epub 2016 May 5.

19

LAD-I: Improved Process Produces VCN >1*

2

1.6

1.2

0.8

0.4

0

Transduction Of HD CD34+ Cells IV

VCN

#102

#104

#102

#104

* Combinations of transduction enhancers demonstrate further doubling or more of VCN (not shown)

Improved process

Old process

Source: Company data on file

Lot #

20

LAD-I Program Summary

Ultra-rare Disease = Streamlined Regulatory Approach

Potential design & endpoints for approval Target Patient Population: Severe LAD-I patients (CD181o VCN~1.5 with latest batcho Tdx enhancers to further enhance VCN

21

Pyruvate Kinase Deficiency (PKD)

Background: PKLR gene mutation shortage of RBC ATP

hemolytic anemia Current available treatment: transfusions, splenectomy GTx potential market est. >250 patients/year

Upcoming Milestones: Rolling IMPD filing in 4Q18

FA

LAD-I

PKD

IMO

AAV

22

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 2018

Clinical Efficacy/Registration Status

Registration & study planning on-schedule Registry efforts underway Rolling IMPD submission in 4Q18 (Spain) US site and PI identified Plan to treat 2 adults, then 2 pediatric patients in Spain 18 post-splenectomy, transfusion-dependent patients pre-

identified in EU

23

Infantile Malignant Osteopetrosis (IMO)

Background: TCIRG1 gene mutation dysfunctional osteoclasts Bone marrow failure, skeletal deformities, frequent

mortality by age 10 Current available treatment: HSCT GTx potential market est. >50 patients/year

Upcoming Milestones: Clinical trials to begin in 2019

FA

LAD-I

PKD

IMO

AAV

24

AAV Program (Undisclosed)

Background: Monogenic multi-organ disease, death in teens without

organ Tx Vector with on-target MOA, tissue specific tropism Current available treatment: Organ Tx Prevalence US/EU: 15,000 to 30,000

Upcoming Milestones: Preclinical data and disclosure of indication in 3Q18 Target IND filing 4Q18

FA

LAD-I

PKD

IMO

AAV

25

AAV: Activity in Mouse Model

Wild-type KO + AAV.EGFP KO + AAV.transgene

Undisclosed collaborator data on file

26

AAV: Expression of Missing Protein in KO mice

3.5

3

2.5

2

1.5

1

0.5

0WT KO GTx Mid GTx HighGTx Low

Undisclosed AAV GTx/GAPDH Ratio

Undisclosed collaborator data on file

27

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 AAV-based GTx

Efforts underway to protect and enhance proprietary technology

Securing protection for continued growth Additional pending patent applications in the US, Europe and Japan relating to devices, methods, and kits for harvesting and genetically modifying target cells

28

World-Class Research and Manufacturing Partners

29

Q1 Q2 Q3 Q4 FA: Updated

patient data AAV: Preclinical

data and first disclosure of indication

FA: Additionalpatient data 4Q18/1H19

AAV: Target IND filing

LAD-I: Target IMPD filing

PKD: Target Rolling IMPD filing

2018 Potential Clinical Value Drivers

Slide Number 1Important InformationSlide Number 3Slide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29

bringing curative gene therapies to patients with rare ... curative gene therapies to patients with...

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