Full Press Release Details
Agenda Time Topic Speaker Duration 8:15 am Introductions and corporate overview Adam
Gridley 15 Minutes 8:30 am Physician Panel - The Clinicians Perspective Dr. DerykJones Dr. Dean Taylor Moderator: Adam Gridley 40 Minutes 9:10 am Care Pathway and Patient Impact - A Patient s Perspective George Pierce
Dr. DerykJones Moderator: Adam Gridley 25 Minutes 9:35 am Break 10 -15 Minutes 9:50 am NeoCart Data Package Adam Gridley 5 Minutes 9:55 am NeoCart Biomechanics and Mechanism of Action Steve Kennedy Larry
Bonassar 30 Minutes 10:25 am NeoCart Launch and Market Access Discussion Don Haut 20 Minutes 10:45 am Pipeline and Financials Jon Lieber 15 Minutes 11:00 am Closing Remarks Adam Gridley 15 Minutes 2 Histogenics
A Leadership Team with a Track Record of Success Adam Gridley, Chief Executive Officer Multiple IPO s and
transactions, global operating/R&D & commercial experience (Merz, BioForm, Gliatech) across devices, drugs & biologics Don Haut, Chief Business Officer Business development, strategic planning, line management and
banking/consulting experience (Medicines Co, Smith & Nephew, JBS, 3M, McKinsey), with over $4 billion of transactions in biotechnology, and medical device businesses Steve Kennedy, Chief Operating Officer Global product development,
manufacturing, technical operations experience leading global clinical and commercial launches (Genzyme, Mascoma, Genencor, MIT) across devices, drugs & biologics Jonathan Lieber, Chief Financial Officer Investment banking & CFO
experience, multiple IPO s & financing & public market experience (Salomon, Cowen / Altus, Repligen, Xcellerex, Metamark) across drugs, diagnostics, tools & biologics 3 Histogenics
Disclaimer Regarding Forward-Looking Statements This presentation includes statements that are, or maybe
deemed, forward-looking statements. All statements, other than statements of historical facts, included in this presentation regarding our strategy, future operations, future financial position, future revenue, projected costs,
prospects, plans and objectives of management are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as may, might, will, objective,
intend, should, could, can, would, expect, believe, anticipate, project, target, design, estimate,
predict, opportunity, proposition, strategy, potential, ongoing, plan or the negative of these terms and similar expressions intended to identify forward-looking
statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Actual results may be materially different. Given these uncertainties, you should not place
undue reliance on these forward-looking statements. Forward looking statements include, but are not limited to, statements about: the timing and success of preclinical studies and clinical trials; the ability to obtain and maintain regulatory
approval of our product candidates in the United States, Japan or in other jurisdictions in which we or our partners may seek such approval; the scope, progress, expansion and costs of developing and commercializing our product candidates; our
expectations regarding our expenses and revenue; the sufficiency of our cash resources and needs for additional financing; our ability to adequately manufacture our product candidates and the raw materials utilized therein; our ability to obtain and
maintain intellectual property protection for our product candidates; our expectations regarding competition; the size and growth of the potential markets for our product candidates and the ability to serve those markets; the rate and degree of
market acceptance of any of our product candidates; our anticipated growth strategies; the anticipated trends and challenges in our business and the market in which we operate; our ability to establish and maintain development partnerships; our
ability to attract or retain key personnel; our expectations regarding federal, state and foreign regulatory requirements; and regulatory developments in the United States and foreign countries and other factors that are described in the Risk
Factors and Management s Discussion and Analysis of Financial Condition and Results of Operations sections of our Annual Report on Form 10-K for the year ended December 31, 2017 and
our Quarterly Report on Form 10-Q for the period ended March 31, 2018, which are on file with the SEC. All of our filings are available on the SEC s website at www.sec.gov. All written and verbal
forward-looking statements attributable to Histogenics or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Histogenics cautions investors not to rely too heavily
on the forward-looking statements Histogenics makes or that are made on its behalf. The information in this presentation is provided only as of the date of this presentation, and Histogenics undertakes no obligation, and specifically declines any
obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. NeoCart is limited by Federal Law to investigational use only and not available for sale. 4 Histogenics
The Histogenics Value Proposition Powerful, proprietary platform that provides restorative cell therapies
(RCTs) for active living Lead product candidate, NeoCart is a proprietary RCT that potentially rebuilds patients own knee cartilage, reducing pain at the source and potentially preventing progression to osteoarthritis (OA) Large market
opportunity to treat knee cartilage damage Phase 3 enrollment complete; data in Q3:18. Near-term value creation opportunity with possible U.S. launch of NeoCart in 2019 Planned expansion of NeoCart platform into additional markets and indications 5
Knee Cartilage Damage: A Complex Problem Cartilage is a complex tissue - shock absorber that must withstand
significant pressure, and allow for rolling and sliding Damage due to acute injury or repetitive trauma Cartilage injury causes pain and loss of function Limited ability to regenerate due to lack of vascularity Strong correlation between knee
cartilage damage and OA Current treatment options are sub-optimal with variable outcomes due to variable cellular response Patients and physicians seeking alternatives that may offer a more rapid and durable
recovery Cartilage Injury Focal Chondral Defect 6 Histogenics
OA Causes Significant Health and Economic Burdens Knee injury increases the risk
of developing OA by more than fivefold ~27 million Americans diagnosed each year with knee OA - with a large portion due to cartilage damage - 1.2 million arthroscopies annually in U.S. associated with cartilage defects; 500,000
procedures including 150,000 microfractures 50% of Americans expected to develop symptomatic knee OA Globally, more than half of patients with knee OA ultimately undergo total join replacement Global direct expenditures for knee OA
treatment are $185 billion annually 7 Histogenics
Limitations of Current Therapies Debridement may reduce pain but does not repair cartilage Microfracture
yields variable outcomes - 30% of microfracture patients continue to have pain and reduced knee function and require additional procedures Current treatments require extensive recovery time and impede return to work and
daily living Current treatments are often ineffective in the long term because they do not adequately address cartilage damage -May lead to additional surgeries -Failure to correct cartilage damage may lead to development of OA 8 Histogenics
Attributes of an Optimal Treatment for Knee Cartilage Damage Reduces pain Improves function Promotes repair of
damaged cartilage Short rehabilitation / more rapid return to daily activities Durable response No specialized surgical techniques and less operating room time Non-opioid approach 9 Histogenics
NeoCart: Restorative Cell Therapy with Novel Mechanism of Action NeoCart combines
breakthroughs in bio-engineering and cell processing to enhance the autologous cartilage repair process NeoCart merges a patient s own cells with a fortified three dimensional scaffold designed
to accelerate healing and reduce pain Patients receive functional cartilage at the time of treatment Follow-up Arthroscopy Demonstrates NeoCart Progression and Integration Initial Lesion Time Zero 8
Weeks 6 Months Implantation Phase 3 patient follow-up arthroscopies unrelated to NeoCart implant. 10 Histogenics
Manufacturing Steps Surgical Steps Assessment of defect & biopsy Cell
isolation & expansion, followed by seeding of 3D scaffold Implant processing in bioreactor under joint- like conditions Continued growth in static culture Manufacturing specifications: tissue histology & clear biomarkers Ex-vivo manufacture of living cartilage tissue with biomarkers & biomechanical data 11 Histogenics
Positive Phase 2 Results Support Phase 3 Trial Design 30 patients at 6 U.S. centers; 2:1 randomization
(NeoCart v. Microfracture) 2011 FDA and 2016 PMDA guidance subjective Pain & Function endpoints, with high hurdle clinically meaningful improvement thresholds: >12 pts KOOS Pain vs. Y1 Baseline, and
>20 pts IKDC Subjective vs. Y1 Baseline 5-year MRI and outcomes data published in Q1:17 IKDC Subjective +20 points Non Responders Non- Responders
+12 points KOOS Pain Non-Responders Responder Superiority Endpoint: % of NeoCart Responders vs Mfx Responders Source: Roos E, Lohmander SL. The knee injury and
osteoarthritis outcome score (KOOS): from joint injury to osteoarthritis. Health Quality Life outcomes. 2003; 1: 64. 12 Histogenics
NeoCart Phase 3 Clinical Trial Based on Successful Phase 2 Trial 1 year primary superiority Endpoint 1 year
primary superiority Endpoint 89% NeoCart Microfracture Evaluable Patients: 21 9 18 9 16 7 *p < 0.05 13 Histogenics
Consistent Improvement in Pain and Function Early (3 mo) yet Sustained Improvement in Pain Median Phase
I & II Scores All Highly Statistically Significant TABLE 2 Change in Patient-Reported Outcomes From Baseline to Each Time Point Parameter Score 3 mo 6 mo 12 mo 24 mo 36 mo 48 mo 60 mo IKDC subjective (n = 29)
6.7 19.0 15.7 19.0* 27.3 18.4* 31.8 19.5* 31.4 21.9* 28.5 27.0* 27.4 20.2* VAS mean (n = 29) -13.5 23.9C -20.8 21.2* -22.5 21.2* -27.9 18.8* -24.2
21.Sb -26.2 21.2* -19.0 27.4C VAS highest (n = 21) -23.2 31.2C -30.2 32.7* -39.8 24.6* -46.6 24.3* -36.8 29.8* -51.5 28.5* -36.4 32.2* KOOS-Pain (n = 21) 11.6
11.1* 19.6 14.1* 21.4 10.4* 22.4 9.4* 22.0 10.0* 23.3 10.8* 21.0 11.2* KOOS-ADL (n = 21) 10.6 15.1 13.6* 16.7 10.7* 18.9
11.5* 15.9 11.1* 16.7 11.4* 16.0 12.4* KOOS-QoL (n =21) 15.6 18,(r <2.9 16.8* 30.7 17.2* 43.4 23.3* 42.2 26.8* 46.7
32.3* 45.4 23.9* KOOS-Symptoms (n = 21) 8.4 15.9 lT TXU-O.S* 18.2 13.2* 20.5 15.3* 20.1 19.9C 21.4 20.8C 22.1 15.1* KOOS-Sports (n =
21) 3.8 29.8 16.4 27.7 22.7* 35.8 22.5* 35.6 25.4* 36.3 24.1* 31.7 28.5* Active ROM (n = 29), deg 1.6 8.6 3.6 &,Sd >4)
8-6 5.7 9.5n 8.2 9.0* 8.6 _1 8.0* 10,7 9.6* Loss to tollew-up/ n 2 0 2-3 1-6 6-8 7 > 9 point KOOS Pain = clinically meaningful Data are reported as mean SD unless otherwise indicated, ADL, Activities of DctH Living; IKDC, International Knee Documentation Committee;
KOOS, Knee injury and Osteoarthritis Outcome Score; QoL, Quality of Lite: HXJftk angc of motion; SF-30, Short Fcrm-36: VAS, visual analog scale, b Statistically
significant difference from tiaaeline; P < 4)01. c Statistically significant difference from baseline: P < ,01, d Statistically significant difference from baseline; P < ,05, e Loss to follow-up
values (n) are variable because of patients omitting I patient-reported outcome at the visit indicated. 14 Histogenics
NeoCart Phase 3 Clinical Trial Key Inclusion Criteria Age: 18-59 Severe and symptomatic cartilage lesions (0.5-6cm2) Femoral condyle and/or trochlear lesions Key Exclusion Criteria Prior lesion treatment High
BMI Significant arthritis Concomitant surgeries Arm 1: NeoCart (n = 169) Arm 2: Microfracture (n = 80) Primary Knee pain/function improvement: ->12 pts KOOS pain ->20 pts IKDC Subjective Secondary Time to full
weight-bearing Failure: Reop or deterioration Collagen layering via MRI Screening n = 249 Endpoints at 1 Year Enrollment completed Q2:17 Topline one-year superiority data anticipated
in Q3:18; potential FDA approval by end of 2019 Trial being conducted under a SPA; may minimize risk of regulatory delays 15 Histogenics
Well-Defined Target Market Seeks Alternative Treatment Options Satisfied with Current Treatments Extremely
likely Likely Neutral Unlikely 75% 25% Dissatisfied or Open to New Therapies Target: Sports medicine physicians seeing patients with knee pain & function loss, regularly performing debridement &
microfracture Surgeons see 10 to 20 patients with cartilage damage each month but treat only 30 40% of these patients due to low satisfaction with the current treatment options Novel products with
1-year clinical superiority to microfracture and minimal training/procedure time may grow the market * Source: Histogenics primary market research with U.S. orthopedic surgeons. 16 Histogenics
Physician Panel Clinician s Perspective Deryk Jones, MD - Section Head of Sports Medicine and Cartilage
Restoration at the Ochsner Sports Medicine Institute Dean Taylor, MD -Director of the Duke Sports Medicine Fellowship Program, Director of the Duke School of Medicine Leadership Education and Development (LEAD) Curriculum, Team Physician, and
Chairman of the Feagin Leadership Program 17 Histogenics
Investigator Panel Introduction & your clinical history with NeoCart
Microfracture surgeons & patient profile How does NeoCart serve an unmet need What are the potential benefits Ease of application, adhesive Unique features Your anecdotal experience with NeoCart - short-term
rehab/recovery and long-term durability Future applications -what is possible with this restorative cell therapy platform vs other products 18 Histogenics
A Patient s Perspective George Pierce 19 Histogenics
Patient Experience - George Pierce Introduction: your lifestyle - work and play
Your microfracture experience & current pain/function for that knee When did you have NeoCart Compare your experiences - rehabilitation, time to work, sitting, squatting Why did you choose NeoCart, and had you considered
Microfracture again How do you feel today, quality of life, ability to work and play with your NeoCart knee Final thoughts -appeals of NeoCart vs current alternate therapies 20 Histogenics
Clinical Data 21 Histogenics
Our Commitment: Growing Body of Clinical Evidence An Autologous Cartilage Tissue Implant NeoCart for Treatment
of Grade III Chondral Injury to the Distal Femur Prospective Clinical Safety Trial at 2 Years Dennis C. Crawford, 1 MD, PhD, Chelsea M. HeveranJ W. Dilworth Cannon Jr,1 MD, Li Foong Foo,5 MD, and Hollis G. Potter,5 MD From the Department
of Orthopaedics, Oregon Health and Science University, Portland, Oregon, the Department of Orthopaedic Surgery, University of California San Francisco Medical School, San Francisco, California, and the Magnetic Resonance Imaging Division,
Department of Radiology and Imaging, Hospital for Special Surgery, New York, New York Background: The healing potential of damaged articular cartilage is limited. The NeoCart is a tissue-engineered collagen matrix seeded with autogenous chondrocytes
designed for the repair of hyaline articular cartilage. Hypothesis: The NeoCart implant is well tolerated in the human knee. Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative
Treatment for Knee Cartilage Injuries Devon E. Anderson,* PhD, Riley J. Williams III,* MD, Thomas M. DeBerardino MD, Dean C. Taylor,5 MD, C. Benjamin Ma,11 MD, Marie S. Kane, MS, and Dennis C. Crawford, 1 MD, PhD Investigation performed
at Oregon Health & Science University, Portland, Oregon, USA Background: Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States
Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture. Hypothesis: Quantitative magnetic
resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60- month follow-up. CoriRiGirr 2012 BY the JOURNAL or BONE AND JOINT SURGERY,
INCORPORATED NeoCart, an Autologous Cartilage Tissue Implant, Compared with Microfracture for Treatment of Distal Femoral Cartilage Lesions An FDA Phase-II Prospective, Randomized Clinical Trial After Two
Years Dennis C. Crawford, MU, PhD, Thomas M. DeBerardino, MU, and Riley |. Williams 111, MD Investigation performed at Oregon Health and Science Center. Portland Oregon, Keller Amry Community Hospital, West Point, New York, Duke Sports Medicine
Center, Durham North Carolina; University of California, San Francisco California; TRIA Orthopaedic Center, Bloomington, Minnesota; and the Hospital for Special Surgery, New York NY Background: Despite introduction of autologous chondrocyte therapy
for repair of hyaline articular cartilage injury in 1994. microfracture remains a primary standard of care. NeoCart, an autologous cartilage tissue implant, was compared with microfracture in a multisite prospective, randomized trial of a
tissue-engineered bioimplant for treating articular cartilage injuries in the knee. Robust Clinical