Gene Therapy, back for good - Deloitte US Therapy, back for good •Some 2015-2016 Gene Therapy deals: •Celgene –Juno $1B (Cancer and autoimmune diseases) •Vertex –CRISPR $2.6B (Gene Editing

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  • Gene Therapy, back for good

    Some 2015-2016 Gene Therapy deals: Celgene Juno $1B (Cancer and

    autoimmune diseases) Vertex CRISPR $2.6B (Gene Editing

    for genetic diseases) BMS UniQure $2.3B

    (cardiovascular) Genzyme Voyager $845M (CNS) Amgen Kite $1.1B (Cancer and

    autoimmune diseases) BioGen Upenn $2B (Genetic

    diseases)

    Some 2015-2016 Gene Therapy IPOs: Nantkwest $238.3M (Cancer)

    Cellectis $228M (Gene Editing, Cancer)

    AdaptImmune $191.3M (Cancer)

    Spark $185.2M (Genetic Diseases)

    RegenexBIO $159.4M (Genetic diseases)

    Voyager $80.5M (CNS)

  • Some morenumbers:

  • What is Gene Therapy?

    Therapeutics that contain DNA and/or RNA

    Hope for a once and for all cure

    A natural therapy

  • First approved U.S. trial

    conducted at the NIH

    1990 2008

    Positive results in the treatment

    Lebers Congenital Amaurosis

    1999 2002

    First fatality reported in a trial for the treatment of ornithine transcarbamylasedeficiency(Jesse Gelsinger)

    Leukemiareported in X-SCID trial

    2011

    Limited positive results in the AAV8 Hemophilia B trial

    2010

    2012

    First AAV based drug approved in

    EU

    Gene Therapy Ups and Downs

    2014

    First Genome Editing

    human trial (ZFN, HIV)

    2013

    Successful T cell Gene Therapy for

    Acutelymphocytic

    leukemia (ALL)

    2015

    Successful Universal CAR-T

    therapy (ALL)

    2016

  • Gene Therapy hottest fields

  • Adeno-Associated Viral vector (AAV)

    - ssDNA vector stable and relatively easy to produce

    - Non-pathogenic - 70-80% of human population have

    been exposed

    - Gutted design - all viral genes are removed from the

    vector

    - Approved therapeutic in E.U. over 30 clinical trials in

    US and E.U

  • AAV Gene Therapy

    - UniQure

    - 4DMT

    - Spark

    - Avalanche

    - AGTC

    - Celladon

    - Voyager

    - Asklepios

    - Dimension

    - Audentes

    - Genethon

    - Regenerex

    Companies to follow:

    Hemophilia

    Choroideremia

  • Genome Editing

    Site specific manipulation of the genome:

    Gene Correction

    Gene insertion

    Gene Deletion

    Leading platforms: CRISPR TALEN ZFN Mega-TAL

  • Gene Editing for Gene Therapy

    HIV

    Cancer

    - Sangamo

    - Cellectis

    - CRISPR

    - Editas

    - Intellia

    - Caribou

    - Precision

    Companies to follow:

  • Gene Immunotherapy

  • Gene Immunotherapy

    - Kite

    - Juno

    - Celgene

    - Bellicum

    - Nantkwest

    - Ziopharm

    - Unum

    Companies to follow:

  • Adenoviral

    Vector

    Retroviral

    VectorLentiviral

    Vector

    Zinc

    FingersTALENs

    CRISPR

    AAV

    Genome Editing

    LogicBio

    12

  • Gene Therapy Gene Editing

    AAV

    No nuclease

    GeneRide

    No promoter

    In vivo

  • AAV-LK03 transduces human cells over 10x better than clinically relevant AAV8

    FRG humanized mice

    1E6-1E8 variants1 variants AAV-LK03

    Lisowski et al Nature, February 2014

    Screen for Novel Vector with Superior Tropism for Primary Human Hepatocytes.

    14

  • ITR

    hF92A

    5 homology arm to Alb 3 homology arm to Alb

    Wild-type Alb locusStop

    +Protein P hF9Alb 2A

    DNA

    Targeted Alb locus hF92A

    RNA Fused mRNA Alb 2A hF9

    Promotorless gene targeting without nucleases

    Barzel et al., Nature 2015

    GeneRide Technology

    15

  • High and stable hF9 plasma levels

    Neonates Adults

    Preclinical Proof of ConceptHemophilia B

    Barzel et al., Nature 2015

    16

  • Normal light conditionPhototherapy treatment

    P 8P 4

    AAV donorDNA injection

    P 30

    Analysis

    P8 Blue

    0 105 15 20 25

    25

    0

    50

    75

    100

    421 3Days Months

    Still alive and well at 12 months ***

    % S

    urv

    ival

    MUT P0-P8 PT

    MUT P0-P8 PT + P4 injection pAlb

    n=7

    n=6

    Preclinical Proof of ConceptCrigler Najjar Syndrome

    17

  • Balazs et al., Nature Immunology, 2013

    0

    5

    10

    15

    20

    25

    30

    35

    40

    control AAV inf no AAV inf

    %C

    D3

    CD

    4 c

    ou

    nt

    Preclinical Proof of ConceptVectored Immunoprophylaxis

    18

  • 19

    Stabilityin dividing tissues

    Safety

    Nucleases

    AAV with promoterAdeno

    Retro and Lenti

    GeneRide

    GeneRide is most compatible for treating both kids and adults

  • Thank you!