#SOTI17

8:00am – 8:20am | Program Introduction & Industry Update Presented by: Morrie Ruffin, Michael Werner and Dr. Robert Preti

8:20am – 9:05am | Cell Therapies: Essential Requirements for Near-Term and Long-Term Commercial Success

Featuring: Bellicum, Kiadis Pharma, Pfizer and bluebird bio

9:05am – 9:50am | The Gene Therapy Pipeline: Will Clinical and Regulatory Progress Match Patient and Investor Expectations?

Featuring: Intellia, BioMarin, AvroBio and Audentes

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Morrie Ruffin Managing Director Alliance for Regenerative Medicine

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About the Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is the preeminent global advocate for regenerative and advanced therapies. ARM fosters research, development, investment and commercialization of transformational treatments and cures for patients worldwide. By leveraging the expertise of its membership, ARM empowers multiple stakeholders to promote legislative, regulatory and public understanding of, and support for, this expanding field.

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•  Advocating for clear, predictable and harmonized regulatory and review pathways •  Enabling market access and value-based, favorable reimbursement policies •  Continued access to capital •  Addressing industrialization and manufacturing hurdles •  Developing and establishing industry-wide standards •  Conducting key stakeholder outreach, communication and education

ARM Focus Areas

ARM takes the lead on the sector’s most pressing and significant issues, including:

Global Landscape

Policy Environment: 2017

Anticipated Clinical Data Events: 2017

Financial Review, Performance & Dealmaking: 2016

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Cell & Gene Therapies State of the Industry: 2017

Clinical Progress: 2016

Michael Werner Executive Director Alliance for Regenerative Medicine

•  FDA review and approval process – o  21st Century Cures is a major win o  Early access policy development &

advocacy o  Modified role for NIH-RAC

•  Global reimbursement issues – o  Identifying potential policy, legal

impediments to coverage and reimbursement for gene/cell therapies and other RM/AT products

o  Developing new reimbursement models o  Payer engagement

•  Standards development – Formal launch of the Standards Coordinating Body

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•  Gene editing & related regulatory, bioethics issues – NAS report; genome editing education

•  PDUFA reauthorization recommendations

•  EU hospital exemption position •  International regulatory convergence •  Patient community education and

outreach •  U.S. presidential election – Transition

team outreach

Current Policy Environment – Key Priorities

•  Major win for patients and RM/AT sector •  ARM served as “hub of the wheel” among key stakeholders through years-long legislative

process o  Bipartisan Congressional offices, FDA, patient organizations, media, trade associations, etc.

•  Optimizes approval pathway & maintains high FDA product approval standards o  Guaranteed interactions with FDA o  Eligibility for priority review & accelerated approval o  Flexibility in number of clinical sites used with possibility of using patient registry and other “real

world” evidence for post-approval studies

•  Directs HHS to work with industry & other stakeholders to create RM standards •  Addresses ARM’s concerns with REGROW Act that sought to change approval pathways

for RM /AT products by reducing FDA’s regulatory authority •  ARM to host webinar on February 2nd to review key RM provisions

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21st Century Cures Act – Major Sector Win

Dr. Robert A. Preti Chairman, Alliance for Regenerative Medicine President, PCT, a Caladrius Company CTO & SVP, Manufacturing & Technical Operations, Caladrius Biosciences

376 in 2015

12 Data provided by:

192 in 2015

63 in 2015

271 Phase I

66 Phase III

465 Phase II

802 Total Clinical Trials: End of 2016 21% growth over 2015

13 Data provided by:

~ 45% of current clinical trials are in oncology ~ 11% are in cardiovascular

Clinical Trials by Therapeutic Category

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Cell & Gene Therapies: Major Therapeutic Platforms & Enabling Technologies

•  Advanced cells: Modified T-cells; Hematopoietic stem cells; iPSCs; MSCs; adult progenitor cells (neural, liver, cardiac); etc.

•  Cell-based immunotherapies: T-cells; CAR-T; TCR; NK cells; TILs; MILs; etc. •  Novel and synthetic gene delivery vehicles: AAV; LV; RV; AD; etc. •  Genome editing: CRISPR/Cas and next-gen CRISPR tech; as well as

TALENs; Zinc finger nucleases; etc. •  Next-gen expression constructs: novel capsids; innovative

regulatory elements, including synthetic promoters that enable specificity, strength, and improve capacity; inducible elements to regulate gene expression temporally or in response to external stimuli: molecular kill switches to improve safety; etc.

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Cell & Gene Therapies: Manufacturing & Industrialization

•  Automated & closed solutions •  Novel tools for genetic engineering & direct development of cell & gene therapies •  Evaluation of business models for optimal clinical development & manufacturing capacity

•  Strategic relationships between developers & companies providing key components & capabilities

•  Commercial production readiness activities •  Demand for standardization & commoditization of manufacturing •  Global harmonization of regulatory requirements

•  Major federal funding initiative through Commerce & DoD to support RM/AT manufacturing infrastructure build out

Major companies active in this space: AAV Vectors •  4D Molecular Therapeutics •  Abeona Therapeutics •  Acucela •  Adverum Biotechnologies •  Agilis Biotherapeutics •  AGTC •  Allergan (Retrosense Tx acquisition) •  Audentes Therapeutics •  AveXis •  Biogen •  BioMarin •  CombiGene •  Dimension Therapeutics •  Esteve •  Freeline Therapeutics •  Genethon •  Gensight Biologics •  Global BioTherapeutics •  Homology Medicines •  HORAMA •  Lysogene •  Milo Biotechnology •  NightstaRx •  Pfizer (Bamboo Tx acquisition) •  REGENXBIO

•  Shire •  Solid Biosciences •  Spark Therapeutics •  Theragene Pharmaceuticals •  uniQure •  Voyager Therapeutics

Lenti/Retroviral Vectors •  Adaptimmune •  AVROBIO •  Bellicum Pharmaceuticals •  bluebird bio •  Calimmune •  Celgene •  Cellular Biomedicine Group •  Cellectis/Pfizer •  Celyad •  Editas Medicine •  EMD Serono •  Errant Gene Therapeutics •  Fate Therapeutics •  Fibrocell Science •  GE Healthcare Life Sciences •  Genenta Science •  GSK •  Immunocore •  Insulete

•  Juno Therapeutics •  Kite Pharma •  MaxCyte •  Medigene •  NexImmune •  Novartis •  Opexa Therapeutics •  Orchard Therapeutics •  Oxford BioMedica •  Poseida Therapeutics/Janssen •  Rocket Pharma •  Takara Bio •  Tocagen •  Unum Therapeutics •  ZIOPHARM Oncology

Adenoviral Vectors •  Angionetics (Taxus Cardium

Pharmaceuticals) •  Cell Medica •  GenVec •  Global Biotherapeutics •  Aevi Genomic Medicine (formerly

Medgenics) •  PeriphaGen •  Renova Therapeutics

Genome Editing •  Biogen •  bluebird bio •  Caribou Biosciences •  Cellectis •  CRISPR Therapeutics •  Casebia Therapeutics (Bayer/CRISPR) •  Editas Medicine •  Homology Medicines •  Intellia Therapeutics •  Poseida Therapeutics •  Precision BioSciences •  Sangamo Therapeutics •  Universal Cells

Enabling Platforms •  Aldevron •  Brammer Bio •  Cell Design Labs •  Cognate BioServices •  EMD Millipore •  Intrexon •  Lonza •  PCT Caladrius •  PharmaCell •  Synpromics •  ThermoFisher Scientific •  WuXi AppTec

Gene Therapy, Gene-Modified Cell Therapy & Genome Editing

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•  Strimvelis EMA approval – GSK’s ex vivo stem cell gene therapy Strimvelis receives European Marketing Authorization to treat very rare disease ADA-SCID – May 27, 2016

•  Spark Therapeutics’ positive Phase III data to treat inherited retinal disease – Spark announces positive data from continuation of Ph III trial of most advanced product candidate, voretigene nepavovec – August 10, 2016

•  Kite Pharma files BLA for first CAR-T therapy in US – Kite announces submission of KTE-C19, investigational anti-CD19 CAR-T Therapy for treatment of relapsed/refractory aggressive b-cell non-Hodgkin lymphoma – December 4, 2016

•  TEMCELL launches in Japan – Mesoblast licensee JCR Pharmaceuticals launches allogeneic cell therapy product TEMCELL in Japan for treatment of acute GvHD – February 24, 2016

•  TiGenix reports positive Phase III data for Crohn’s – TiGenix announces 52-week results of Cx601 in complex perianal fistulas in Crohn’s disease patients – March 7, 2016

•  FDA approves Vericel’s Maci – First autologous cellularized scaffold, for the repair of cartilage defects of the knee – December 13, 2016

•  BioMarin provides positive Ph I/II data for hemophilia – BioMarin announces interim results of BMN 270 gene therapy for treatment of severe hemophilia A – July 27, 2016

•  Novartis presents pivotal data from first global CAR-T therapy trial – Novartis reports positive data from pivotal trial of CTL019 CAR-T cell therapy for treatment of r/r ALL – December 4, 2016

•  ReNeuron reports positive results in Ph II stroke trial – ReNeuron announces data from study of CTX cell therapy in patients with stroke disability – December 5, 2016

Major Clinical Milestones & Key Data Events: 2016

Company Therapy/Product Therapeutic Modality Indication Clinical Stage Expected Reporting Date

Kite KTE-C19 Anti-CD19 CAR-T Cell Therapy Chemorefractory aggressive non-Hodgkin lymphoma

US/EU Marketing Approval

Primary analysis (6 month follow-up), BLA submission Q1 2017; Commercial US launch, EMA regulatory submission 2017

Spark Voretigene Neparvovec

AAV-Mediated Gene Therapy RPE65-mediated inherited retinal disease

US Marketing Approval

BLA submission early 2017

Novartis CTL019 CAR T-Cell Therapy r/r pediatric B-cell ALL US Marketing Approval

BLA submission early 2017

TiGenix Cx601 Cell Therapy Complex perianal fistulas in Crohn’s disease

EU Marketing Approval

EMA approval 2H 2017

Kiadis Pharma ATIR101 Allodepleted T-Cell Immunotherapy AML or ALL EU Marketing Approval

EMA submission Q1 2017

Argos Tx AGS-003 Cell Immunotherapy Renal cell carcinoma Ph III Mid-2017

Cytori ECCS-50 Adipose-Derived Regenerative Cell Therapy

Scleroderma hand dysfunction Ph III First readout mid-2017; 12 month data YE 2017

Mesoblast MPC-150-IM Mesenchymal Precursor Cell (MPC) Therapy

Congestive heart failure Ph III Interim analysis 1H 2017

Mesoblast MPC-06-ID Mesenchymal Precursor Cell (MPC) Therapy

Chronic low back pain due to disc degeneration

Ph III Interim analysis 1H 2017

bluebird bio LentiGlobin BB305

Lentiviral-Based Gene Therapy Transfusion-dependent B-Thalassemia

Ph III 2017

Some Major Anticipated Clinical Data Events: 2017

Some Major Anticipated Clinical Data Events: 2017 Company Therapy / Product Therapeutic Modality Indication Clinical Stage Expected Reporting Date

TiGenix AlloCSC-01 Cell Therapy Acute myocardial infarction Ph II 1H 2017

Bone Therapeutics ALLOB® Allogeneic Cell Therapy Spinal fusion Ph IIA Summer 2017

Asterias AST-OPC1 Cell therapy Cervical spinal cord injury Ph I/IIA 6 month results Q1 2017

Capricor CAP-1002 Allogeneic Cardiac Cell Therapy Duchene muscular dystrophy Ph I/II Top-line 6 month results Q2 2017

Dimension Tx DTX101 AAV-Mediated Gene Therapy Hemophilia B Ph I/II Q1 2017

Fibrocell FCX-007 Gene Therapy Personalized Biologic

Recessive dystrophic epidermolysis bullosa (RDEB)

Ph I/II First clinical data Q3 2017

BioMarin BMN 270 Gene Therapy Hemophilia A Ph I/II Q1 2017

Voyager VY-AADC01 AAV-Mediated Gene Therapy Advanced Parkinson’s disease Ph IB 1H 2017

bluebird bio/Celgene bb2121 CAR T-Cell Immunotherapy r/r multiple myeloma Ph I 2017

Cellectis / Servier / Pfizer

UCART19 Gene Edited CAR T-Cells ALL, CLL Ph I Interim data 1H 2017

AveXis AVXS-101 Gene Therapy Type 1 SMA Ph I Top-line data Q1 2017

Audentes AT132, AT342, AT982

AAV-Mediated Gene Therapy X-Linked Myotubular Myopathy, Crigler-Najjar Syndrome, Pompe Disease

Pre-Ph I Preliminary data from each indication EOY 2017

Pluristem PLX-R18 Placenta-Based Cell Therapy Acute radiation syndrome Pre-Ph I 1H 2017

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•  Biogen & UPenn enter into $2B collaboration on multiple gene therapy programs, upfront payment of $20M – May 16, 2016

•  Pfizer acquires Bamboo Therapeutics in $645M deal, $150M upfront – August 1, 2016

•  Adaptimmune & GSK expand immunotherapy collaboration to $500M from $300M – February 2, 2016

•  bluebird bio & Medigene establish $1B+ strategic TCR immunotherapy R&D collaboration & licensing agreement, $15M upfront – September 29, 2016

•  Baxalta signs $1.7B agreement with Precision Biosciences, Inc., $105M upfront – February 25, 2016

•  Regeneron signs agreement with Intellia Therapeutics to develop CRISPR/Cas therapeutics, $75M upfront – April 11, 2016

•  Takeda & TiGenix enter into €355M licensing agreement for ex-U.S. rights to Cx601, €25M upfront to TiGenix – July 5, 2016

•  Healios K.K. & Athersys enter into $240M partnership for treatment of stroke using Athersys MultiStem Therapy, $15M upfront – January 8, 2016

•  Allergan acquires LifeCell regenerative medicine business unit from Acelity in $2.9B cash deal – December 20, 2016

•  Celgene & Evotec enter into $250M exclusive iPSC R&D collaboration, Evotec to receive $45M upfront – December 15, 2016

•  Bayer & Versant Ventures launch iPSC therapy company BlueRock Therapeutics with $225M Series A Financing – December 12, 2016

•  Spark Tx enters into licensing agreement with Selecta Biosciences, $10M upfront – December 5, 2016

Data provided by:

Examples of Key Corporate Partnerships: 2016

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Examples of Key IPOs: 2016

•  Intellia Therapeutics IPO raises $124.2M – May 11, 2016

•  Editas Medicine IPO raises $108.6M – February 8, 2016

•  AveXis, Inc. IPO raises $95M – February 10, 2016

•  Audentes Therapeutics IPO raises $85.1M – August 20, 2016

•  CRISPR Therapeutics IPO raises $56M – October 18, 2016

•  GenSight Biologics IPO raises €45.2M on Euronext Paris Stock Exchange – August 11, 2016

•  TiGenix US IPO raises $35.7 – December 20, 2016

•  MaxCyte, Inc. IPO raises $14.2M on London Stock Exchange – March 29, 2016

•  Cellect Biotechnology Ltd. IPO raises $8.4M – August 3, 2016

Data provided by:

Total Financings: 2016 $5.3 Billion

Total Amount Raised in 2016

$11 Billion raised in 2015

$461 Million Tissue Engineering $812 Million raised in 2015

$2.8 Billion Gene & Gene-Modified

Cell Therapy $6.9 Billion raised in 2015

$3.0 Billion Cell Therapy

$7.0 Billion raised in 2015

Data provided by: ** Please note: total amount raised represents sector-wide figures; some companies are active in more than one technology group.

*in USD

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Total Financings by Type: 2016

Data provided by: *in millions USD

Total Financings by Type, by Year

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84.8%

123.5%

78.3%

107.5%

60%

80%

100%

120%

140%

160%

180%

12/31/15 3/31/16 6/30/16 9/30/16 12/31/16

GeneTherapyAverage 2016IPOAverage NasdaqBiotechnology Index% NasdaqIndex%Gene Therapy Average RM/AT IPO Average Nasdaq Biotech Index % Nasdaq Index %

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Advanced Therapies Public Company Performance: January 2016 – December 2016

Data provided by:

As of 12/31/16

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Key Takeaways

•  RM/AT sector continues to show momentum year-over-year

•  Clinical pipeline is robust and growing

•  Continued improvements in CMC strategies & processes

•  Significant number of late stage data events anticipated in 2017 & 2018

•  Sustained investor activity indicates belief in sector growth potential

•  ARM well-positioned to continue thought leadership on policy issues

Data provided by:

Special thanks to our data partner:

ROBERT PRETI CHAIRMAN, ARM; PRESIDENT, PCT; CTO & SVP, CALADRIUS BIOSCIENCES

MODERATOR

THOMAS FARRELL PRESIDENT & CEO, BELLICUM PHARMACEUTICALS

MANFRED RÜDIGER CEO, KIADIS PHARMA

BARBRA SASU VP ALLOGENEIC CAR T PLATFORM, PFIZER

JEFFREY WALSH CHIEF FINANCIAL & STRATEGY OFFICER, BLUEBIRD BIO

PANELISTS

Cell Therapies: Essential Requirements for Near-term and Long-term Commercial Success

SARAH HAECKER MEEKS CHIEF SCIENTIFIC OFFICER, ADJUVANT PARTNERS &

DIRECTOR, TECHNOLOGY SECTIONS, ARM

NESSAN BERMINGHAM CEO, PRESIDENT & FOUNDER, INTELLIA THERAPEUTICS

CHRIS MASON CHIEF SCIENCE OFFICER, AVRO BIO

MATTHEW PATTERSON PRESIDENT & CEO, AUDENTES THERAPEUTICS

The Gene Therapy Pipeline: Will Clinical and Regulatory Progress Match Patient and Investor Expectations?

MODERATOR

PANELISTS