Dr. Robert Preti Chairman, Alliance for Regenerative Medicine President, PCT, a Caladrius Company

#CGDay17

ARM Cell & Gene Therapy Investor Day April 27, 2017 | Boston, MA

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•  Advocate for clear, predictable and harmonized regulatory and review pathways •  Enable market access and value-based, favorable reimbursement policies •  Facilitate sustainable access to capital and identify sources of potential public funding •  Address industrialization and manufacturing hurdles •  Conduct key stakeholder outreach, communication and education

ARM Strategic Priorities: 2017

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•  Signed into law Dec 13, 2016 •  Major win for patients and RM/AT sector •  ARM served as “hub of the wheel” among key stakeholders through years-long legislative process:

Bipartisan Congressional offices, FDA, patient organizations, media, trade associations, etc. •  Introduces, for the first time in the U.S., a specific RM/AT product designation •  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/AT 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 hosted webinar Feb 2 to review key RM provisions, available on ARM’s website

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21st Century Cures Act – Major Sector Win

#CGDay17

Global Landscape #CGDay17

5 Data provided by:

855 Total Clinical Trials: Q1 2017

270 Phase I

68 Phase III

517 Phase II

#CGDay17

6 Data provided by:

Nearly 50% of current clinical trials are in oncology ~ 10% are in cardiovascular

#CGDay17

Clinical Trials by Therapeutic Category: Q1 2017

1 1 1 2 3 8 9 10 15 20

28 35 35 36 40

47 59

89 413

Geriatric Diseases Dental

Radiation Injury Ear Diseases

Lymphatic Diseases Surgery

Genitourinary Disorders Respiratory

Gastroenterology Hematology

Ophthalmology Immunology and Inflammation

Endocrine, Metabolic & Genetic Disorders Dermatology

Infectious Diseases Musculoskeletal

Central Nervous System Cardiovascular

Oncology

0 50 100 150 200 250 300 350 400 450

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RM/AT stands to dramatically impact standard of care for patients in key therapeutic areas: oncology, cardiovascular disease, wound healing and tissue repair, ophthalmological disorders, neurodegenerative disease, diabetes and more.

Companies developing various next-gen 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; ZFNs; 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.

Upcoming Innovations Sector-Wide

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•  Kiadis files marketing authorization with EMA for ATIR101 in blood cancers – April 26, 2017 •  Kite Pharma files BLA for first CAR-T therapy in U.S. – Kite completes submission of U.S. BLA for

KTE-C19 as first CAR-T therapy for treatment of aggressive non-Hodgkin lymphoma – March 31, 2017 •  Novartis files first CAR-T cell therapy BLA for pediatric and young adult patients with r/r B-cell ALL;

FDA grants Priority Review – March 29, 2017 •  FDA approves Vericel’s Maci – First autologous cellularized scaffold, for the repair of cartilage defects of

the knee – December 13, 2016 •  Spark Therapeutics’ positive Ph III data to treat inherited retinal disease – Positive data from

continuation of Ph III trial of most advanced product candidate, voretigene nepavovec – August 10, 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 •  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 •  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 •  TEMCELL launches in Japan – Mesoblast licensee JCR Pharmaceuticals launches allogeneic cell

therapy product TEMCELL in Japan for treatment of acute GvHD – February 24, 2016

#CGDay17

Select Key Regulatory Milestones & Key Data Events: 2016 & Q1 2017

Company Therapy/Product Therapeutic Modality Indication Clinical Stage Expected Date

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

US/EU Marketing Approval

Potential commercial launch & EMA regulatory submission 2017

Spark Tx Voretigene Neparvovec

AAV-Mediated Gene Therapy RPE65-mediated inherited retinal disease

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

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

Select Anticipated Late-Stage Clinical Data Events: 2017

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•  Kite Pharma signs $250M agreement with Daiichi Sankyo Company Ltd, $50M upfront – Jan 9, 2017

•  Allergan and Editas enter into CRISPR R&D alliance, $90M upfront to Editas – March 14, 2017

•  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

•  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

Data provided by:

Select Key Corporate Partnerships: 2016 & Q1 2017

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Select Major Financings: 2016 & YTD 2017

•  Kite Pharma closes $409.7M public offering of common stock – March 8, 2017 •  Bayer AG & Versant Ventures launch BlueRock Therapeutics with $225M series A – December 12, 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 •  Mustang Bio closes $94.5M in private placement – February 2, 2017 •  Editas Medicine announces $90M public offering of common stock – March 16, 2017 •  Audentes Therapeutics IPO raises $85.1M – August 20, 2016 •  REGENXBIO announces $75.9M public offering of common stock – March 21, 2017 •  Audentes Therapeutics announces $75.4M public offering of common stock – April 18, 2017 •  Bellicum closes $69M in public offering of common stock – March 30, 2017 •  CRISPR Therapeutics IPO raises $56M – October 18, 2016 •  GenSight Biologics IPO raises €45.2M on Euronext Paris Stock Exchange – August 11, 2016 •  TiGenix U.S. IPO raises $35.7M – December 20, 2016

Data provided by: #CGDay17

Total Financings: 2016 & Q1 2017 $2.5 Billion

Total Amount Raised in Q1 2017

$5.1 Billion total raised in 2016

$229 Million Tissue Engineering

in Q1 2017 $425 Million total raised in 2016

$1.0 Billion Gene & Gene-Modified

Cell Therapy in Q1 2017 $2.7 Billion total raised in 2016

$1.9 Billion Cell Therapy in Q1

2017 $2.9 Billion total raised in 2016

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

*in USD #CGDay17

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Total Financings by Type: Q1 2017

Data provided by: *in millions USD

$823

$198

$100

$263

$1,102

$0 $200 $400 $600 $800 $1,000 $1,200

Follow-Ons

Corporate Partnerships Upfront Pmts

VC Financing

PIPES

M&A Upfront Pmts

#CGDay17

Total Financings by Type, by Year

14 Data provided by: *in millions USD

$577

$847

$647

$1,165

$872

$1,052

$1,672

$2,244

$2,316

$1,819

$974

$1,762

$1,479

$1,225

$314

$1,028

$744

$526

$0 $500 $1,000 $1,500 $2,000 $2,500

IPO

Follow-Ons

Corporate Partnerships Upfront Pmts

VC Financing

PIPES

M&A Upfront Pmts

2014

2015

2016

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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 this year

•  Sustained investor activity indicates belief in sector growth potential

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

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Special thanks to our data partner: