UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
Current Report
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event Reported): June 19, 2018
HISTOGENICS CORPORATION
(Exact Name of Registrant as Specified in its Charter)
| Delaware | 001-36751 | 04-3522315 | ||
| (State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification Number) |
830 Winter Street, 3rd Floor
Waltham, Massachusetts 02451
(781) 547-7900
(Addresses, including zip code, and telephone numbers, including area code, of principal executive offices)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 7.01. | Regulation FD Disclosure. |
Histogenics Corporation (“Histogenics”) will be hosting its first Investor Day and live webcast on Tuesday, June 19, 2018, in New York City. Members of Histogenics’ management team will provide a corporate overview and discuss the commercialization plan for NeoCart®, Histogenics’ lead investigational product, designed to rebuild a patient’s own knee cartilage to treat pain at the source and potentially prevent a patient’s progression to osteoarthritis. Histogenics’ management will be joined by leading orthopedic surgeons who will provide their clinical perspectives on NeoCart, as well as market access insights into today’s orthopedic marketplace. The program will also include perspectives from a patient that received NeoCart in the Phase 3 clinical trial as well as additional content related to Histogenics’ technology platform including a discussion on tissue engineering and the biomechanics of cartilage tissue. The slides that will be used for such presentation are furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Various statements to be made during the Investor Day and webcast are “forward-looking statements” under the securities laws. Words such as, but not limited to, “anticipate,” “believe,” “can,” “could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,” “might,” “objective,” “plan,” “predict,” “project,” “target,” “likely,” “should,” “will,” and “would,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties.
Important factors that could cause actual results to differ materially from those reflected in Histogenics’ forward-looking statements include, among others: the timing and success of Histogenics’ NeoCart Phase 3 clinical trial, including, without limitation, possible delays in generating the data from the clinical trial; the ability to obtain and maintain regulatory approval of NeoCart or any product candidates, and the labeling for any approved products; NeoCart’s regulation as a Regenerative Medical Product in Japan; the market size and potential patient population in Japan; the scope, progress, expansion, and costs of developing and commercializing Histogenics’ product candidates; the ability to obtain and maintain regulatory approval regarding the comparability of critical NeoCart raw materials following our technology transfer and manufacturing location transition; the size and growth of the potential markets for Histogenics’ product candidates and the ability to serve those markets; Histogenics’ expectations regarding its expenses and revenue; 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 Histogenics’ Annual Report on Form 10-K for the year ended December 31, 2017 and Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, which are on file with the Securities and Exchange Commission (“SEC”) and available on the SEC’s website at www.sec.gov. In addition to the risks described above and in Histogenics’ annual report on Form 10-K and quarterly reports on Form 10-Q, current reports on Form 8-K and other filings with the SEC, other unknown or unpredictable factors also could affect Histogenics’ results.
There can be no assurance that the actual results or developments anticipated by Histogenics will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Histogenics. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved.
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 conveyed on during the Investor Day and webcast will be provided only as of the date of the Investor Day, and Histogenics undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements made during the call after the date thereof, whether as a result of new information, future events or otherwise.
The information in Item 7.01 of this Current Report on Form 8-K and the Exhibit attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
|
Exhibit No. |
Description | |
| 99.1 | Presentation Slides. |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: June 19, 2018 | HISTOGENICS CORPORATION | |||||
| By: | /s/ Adam Gridley | |||||
| Adam Gridley | ||||||
| President and Chief Executive Officer | ||||||
Exhibit 99.1
Exhibit 99.1 Histogenics Restorative Cell Therapies for Active Living Investor Day June 19, 2018
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 Histogenics
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% â– NeoCart â– 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
Data Package: • One of the most
rigorously studied RCTs for orthopedic use - Phase 1 (n=9), Phase 2 (n=30), and Phase 3 (n=249), clear level 1 published evidence • Only rapid-onset RCT with a one-year primary superiority endpoint under
SPA in a Phase 3 trial, high hurdle dual threshold pain/function endpoints •Rapid Recovery as measured by HEOR endpoints + Long¬term Durability (3-year data in many patients already). Expect up to 7-year data via registry We collect cartilage biomarkers for every NeoCart Further MOA data via biomechanical testing with Cornell •Developing further evidence of how NeoCart works, and the importance of
providing tissue, structure and ECM •Based on FDA request initially, now broadening collaboration to further characterize our unique RCT platform and identify future product oppties 22 Histogenics
NeoCart Biomechanics and Mechanism of Action Lawrence Bonassar, PhD - Scientific Advisory Board, Histogenics Corporation, Professor in the Meinig School, of Biomedical Engineering and the Sibley School of Mechanical and Aerospace Engineering at Cornell University 23 Histogenics
Histogenics/Cornell Sponsored Research Agreement Sponsored Research Agreement (SRA) initiated in 2014 - Bonassar Lab, Meinig School of Biomedical Engineering/Sibley School of Mechanical and Aerospace Engineering, Cornell University - Original Aims 1.Develop 3D printing methods for cartilage manufacturing 2.Biomechanical test methods for NeoCart -Current Aims 1.Use of non-invasive optical techniques to measure structure and composition of NeoCart constructs 2.Examine the relationship between measurement of local structure, composition, and mechanical properties of NeoCart constructs 3.Apply techniques for process control and validation of NeoCart constructs • 2011 FDA guidance regarding biomechanical testing of cartilage constructs - Histogenics/Cornell SRA is most comprehensive effort to date, setting the standardfortheindustry 24 Histogenics
New Paradigm for Mechanical Analysis Stationary Shearing Movable Piezoelectric Actuator shearing Plate Aggregate modulus (kPa) permeable Piston chamber • Multi-modal analysis of NeoCart performance - Customized devices to measure performance in compression, shear, friction -Implant-scale performance and micromechanical analysis •Longitudinal analysis of batches over 3 years -Analysis of the effects of cell source, patient batch, material source -Largest data set on assessment of performance of a cartilage repair product (336 independent combination of sample/test) 25 Histogenics
Initial NeoCart Biomechanical Test Data Presented in February 2016 at ORS NeoCart macro-scale biochemical and biomechanical properties approach those of native cartilage prior to implantation No other tissue-engineered product on the market with these characteristics Results Macroscale Mechanical Characteristics of Constructs Improve Over Culture Time C Mechanical Characterization of Autologous Chondrocyte- Seeded Matrix Grafts After In Vitro Growth Jill Middendorf1; Darvin Griffin2; Stephen Kennedy3; Sonya Shortkroff* Caroline Dugopolski’Joseph Siemiatkoski3; Lena Bartel!4; Itai Cohen5; Lawrence Bonassar’‘2 ’Sibley School of Mechanical and Aerospace Engineering; 2Meinig School of Biomedical Engineering; 4School of Applied and Engineering Physics; sDepartment of Physics; Cornell University; ’Histogenics Corporation, Waltham, Massachusetts A, Aggregate modulus increased overtime to a value half that of human cartilage. B) Hydraulic permeability decreased over time to twice that of human cartilage. C) sGAG content increased to values similar to human cartilage. D)Friction coefficient plateaued at values similar to human cartilage. E)Surface roughness values decreased over time to values similar to human cartilage. F)Global shear modulus of samples remained an order of magnitude less than human cartilage. (*p<0.05 compared to 0 week value, “p<0 0S compared to human cartilage; n=7-8 constructs, n = 3 human cartilage) 26 Histogenics
NeoCart Micro-scale Properties Presented in February 2016 at ORS I Mechanical properties are controlled by extracellular matrix in developed tissue Cells and scaffold only results in scaffold buckling under strain Microscale Mechanical Characteristics of Constructs Change Over Culture Time A) Axial compression Histology videos show 0% Axial Compression (Saf-O) 5% Axial Compression 10% Axial Compression > scaffold buckling in less developed tissue resulting in areas of high axial strain Arrows indicate buckled scaffo ds B ) More developed constructs resist scaffold buckling and results in areas of high axial strain at or near s construct surface High Shear Strain Occurs at Buckling Locations or Construct Surface sGAG Reduces Bucking Depth (pm) Depth (pm) Buckling 7 Weeks 3 Weeks 27 Histogenics
200 (C) Cornell University 2016 200 (C) Cornell University 2016 NeoCart Micromechanics Confocal elastography provides key insights into the maturation mechanism of NeoCart - Compression of early stage constructs with minimal fill causes buckling in scaffold pores - After in vitro cultivation new matrix deposition reinforces pores and prevents buckling Novel mechanical analysis technique provides new framework for QA/QC -Replaces arbitrary target with observation with clear transition in mechanical behavior -Amenable to correlation with non-destructive, in-line imaging 1 Week 7 Weeks 28 Histogenics
Mechanical Characteristics of Cartilage Produced from Induced Pluripotent Stem Cells (iPSC’s) Cartilage tissue generated using iPS cells with similar mechanical properties as that of tissue produced using native chondrocytes 29 Histogenics
Next Steps Utilizing biochemical and biomechanical test methods for NeoCart characterization in BLA filing, per FDA Guidance • Developing non-invasive methods for in-process monitoring • Applying techniques in Advanced Regenerative Manufacturing Institute (ARMI) partnership to ligament, bone and nerve tissues, with partners 30 Histogenics
Potential NeoCart Launch and Market Access Discussion 31 Histogenics
NeoCart – The New Standard of Care vs. Microfracture Potential Patient Benefits and Outcomes • Pain relief and return to function in typically V the time • Better QOL, improved productivity •Fewer rehab and recovery days •Excellent safety profile •Early pain relief may result in less use of pain medication Potential Physician Benefits •Robust clinical data - 1-year superiority endpoint •Functional tissue at the time of implantation •Uncomplicated 30-minute procedure •No special surgical training required •Happy patients build practices Potential Payer Cost Effectiveness •Lower overall total cost of care •Less costly rehab •Less use of opioids and faster return to work •Delay and prevent OA progression and total knee replacement •Fewer re-ops (30% failure rate of microfracture) “Get Your Life Back!” 32 Histogenics
A Focused Launch Plan Year One Objectives • Establish a core of high-volume customers with deep knowledge of NeoCart • Develop a core body of knowledge around product use in the market •Institute strong training, and certification program •Establish a solid platform for logistics, and service •Build a foundation with payers Lay the groundwork for significant growth in years 2 and 3 Focused Launch Clinical Partners and associated surgeons (<90) Surgeons, staff and institutions already have experience with NeoCart Minimal training requirement 33 Histogenics
Commercial Execution Priorities Surgeon Selection Market Access • High volume per surgeon • Experienced with product •Institutional experience with process •Carve-out code •Benefit decisions with key insurers •Limited requirements for prior treatment •Easy •Reliable •Focused on supporting practice operations 34 Histogenics
Medical Affairs Team Built Strong Relationships in Clinical Trials Surgeons Value the NeoCart Partnership Grow their practice with innovative products Help them differentiate against their peers and attract more patients Happy patients bring additional patients to their practice - “everyone has or knows someone with knee pain!” Deryk Jones, MD Scott Hacker, MD Joseph Guettler, MD Robert Grumet, MD 35 Histogenics
Initial U.S. Commercialization Targets • Phase 3 clinical sites amongst the highest volume sites • Initial focus of sales force: physicians already experienced with NeoCart patient benefits and ease of use •Total of 87 physicians at these sites seeing approximately 1,300 patients per month 36 Histogenics
We Can Potentially Use Existing Codes for ACI Existing codes are applicable to NeoCart (partial list) Code System Code Description3 HCPCS J7330Autologous cultured chondrocytes, implant CPTS2112Arthroscopy, knee, surgical for harvesting of cartilage (chondrocyte cells) CPT27412Autologous chondrocyte implantation, knee • Focus on small number of surgeons enables laser focus on only the most impactful payers in the first year •Orderly progression for following years •Helps to build the foundation for strong growth in years two and beyon 37 Histogenics
Most Insurers Already Cover ACI (representative list) 38 Histogenics
Coverage Requirements Generally Not Restrictive Generally adults under the age of 55 Varies, most have minimum of 1.5 cm2 - 2 cm2 Common Exclusions: Age: Size: Location: Most include femoral condyle only (medial, lateral, trochlea) Grade: Full-thickness (grade III or IV) Prior Treatment: Varies • All require failure of conservative treatment • Many require failure of prior surgical treatment (including debridement) •Some require failure of microfracture or other procedure Osteoarthritis Lesions of the patella Kissing lesions Total meniscectomy 39 Histogenics
Customer Service Will Largely Be Outsourced To Tier 1 Partners Multiple Well Established Vendors for Customer Service Pre-authorization Patient Support Reimbursement & Appeals Support Scheduling & Process Transparency Logistics & Distribution Practice Management Will Be Run In-house Practice Management • Local specialized clinical recruiting/marketing was a critical component of our trial enrollment success • Become a business partner to help grow practices •Drive interested patients to certified NeoCart providers 40 Histogenics
Working Together To Build A Platform For Growth Medical Affairs Commercial MSL’s • Inform, create interest • Train •Certify •Some case coverage initially Account Execs •Institutional bureaucracy •Contracting •Occasional case coverage •Coordination of service elements •Practice management 3rd Party Service • Pre-authorization •Logistics and scheduling •Appeal assistance •Patient support • Ownership of accounts • No Ownership of accounts 41 Histogenics
Anticipated Year 1 Commercial Organization Providers CBO VP of Marketing VP of Market Access VP of Sales Product Manager 3rd Party Providers Area Sales Exec (7) Trade Show Coordinator Practice Mgmt Specialist (2) Training Manager 3rd Party Service Providers Years 2 and 3 Expect: • Additional sales reps • Additional sales management •National accounts •Additional marketing 42 Histogenics
Our Commercial Plan The New Standard of Care for Cartilage Lesions Real Tissue to Get Your Life Back Partner with Medical Affairs in a Focused Launch Year 1 Customer Selection, Market Access, Customer Service 43 Histogenics
Pipeline and Financials 44 Histogenics
Technology Platform Supports Long Term Strategy to Build Value Maximize U.S. NeoCart Opportunity Leverage Histogenics’ Technology Platform Continue to Develop Manufacturing Capabilities and Build Out Manufacturing Capacity 45 Histogenics
Strong Competitive Position Regulatory pathway creates complex barrier to competition • BLA pathway and SPA • Phase 2 demonstrated 1-year superiority leading to Phase 3 trial design Robust intellectual property •More than 85 global and 45 U.S. owned and licensed patents covering cell culture, bioreactors and materials; provide broad coverage for methods in cartilage production and tissue sciences Coverage through 2031 cGMP manufacturing process and facility •Autologous process; no generic substitute •In-house manufacturing of raw materials results in greater control and enables potential improvements in gross margin 46 Histogenics
Multiple Opportunities for Value Creation Multiple value inflection points through continued advancement of NeoCart platform Leveraging 15 years of CMC investment, significant CMC biologics and raw materials expertise International Expansion • Japan (MEDINET) • OUS Partnering Indication tpansion Ankle Shoulder Toe Allogeneic Expansion Intrexon Collaboration Tissue Type Expansion Ligaments Pediatric Vascular Grafts 47 Histogenics
Leveraging the RCT Platform Armi $87M partnership for Japan commercialization and development rights completed in December 2017 $10M up-front payment; up to ~$77M in additional milestones 30 Patient Ph3 bridging study begins in H2:18 leading to potential launch in 2021 Large market with reimbursement in place at ~$20,000 USD Tiered royalties rising to low double digits with increasing annual sales Exploring additional International partnerships (e.g. China, Korea) Research collaborations with leading universities and institutions NeoCart BLA support Manufacturing initiatives to reduce COGs including 3-D tissue printing and optical testing Additional product opportunities in soft tissues, bones and nerves * Source: Histogenics primary market research with Japanese orthopedic surgeons (n=80) 48 Histogenics
World-Class Advisory Board and Academic Collaborations Academic Collaborations Dr. Shuichi Mizuno: Assistant Professor, Orthopedic Surgery, Harvard University /Brigham Women’s (Histogenics Technical Founder), ongoing collaborations for HA / Col Gel Formulations Dr. Lane Smith: Department of Orthopedic Surgery, Stanford University. Decades of cartilage research experience, Licensed Patents Dr. Kerry Athanasiou: UC Irvine, Distinguished Professor BioMedical Engineering, Orthopedic Surgery Dr. Charles Cooney: MIT Professor of Chemical Engineering (Emeritus). Board of Directors at Genzyme, Focus on Biopharmaceutical Manufacturing, Carticel experience, Biologics including original process engineering work with Genentech Dr. Lonnie Shea: University of Michigan Department of BioMedical Engineering. Department Chair. Working at intersection of scaffolds and biologics, including regeneration of axons, donor islet cells. Dr. Jennifer Elisseeff: Johns Hopkins Department of Biomedical Engineering - Cartilage regeneration, hydrogels, stem cells, Industry friendly, founder of several companies Dr. Lawrence Bonassar: Cornell University MeinigSchool of Biomedical Engineering and Sibley School of Mechanical and Aerospace Engineering, leader in cartilage biomechanics and tissue engineering, ongoing collaborations for biomechanical testing of NeoCart 49 Histogenics
NeoCart Growth Opportunity & Key Financial Metrics Gross Margin Right axis Units Left axis Oppty for Cost Reduction Rent and VolumeManufacture in lower cost env; significant reduction in COGs AutomationReduction in labor and testing costs New Mfg. TechnologiesMulti-unit Tep (lower COGs and ability to scale); optical QC testing Raw MaterialsBringing remaining raw materials in-house Allogeneic ProductLikely necessary to get to more than 10k NeoCarts/year and to increase margins > 80% 80% 70% 60% 50% Gross Margin Key Market Metrics ->1M patients with cartilage defects WW -Multi-billion dollar market opportunity -~$40K price point (based on publicly available competitor information) Key Financial Metrics -Cash runway into Q4:18 -~28.7M primary shares o/s; ~45.5M FD -Cash and mktbl securities @ 3/31/18: ~$15.5M 50 Histogenics
Conclusion 51 Histogenics
Progress on the Path to Commercialization and Launch Completed: FDA raw materials approved - collagen and scaffold Acquisition of Japanese NeoCart product rights Publication of Phase 2 MRI and clinical outcomes data Publication of NeoCart mechanical data Japanese regulatory pathway established NeoCart Phase 3 trial fully enrolled NeoCart Japanese licensing agreement H1 2018 H2 2018 H1 2019 H2 2019 Top line Ph 3 Data and BLA Filing Data Presentations: Cornell and others, Phase 3 Clinical Trial Japanese Phase 3 Clinical Trial Additional Manufacturing Capacity Med Affairs Planning, KOL Devt, Training and Patient Education Initiatives Additional business development activities - new territories, products etc. Next Gen Preclinical Studies Hire and Train Sales Force (U.S. Approval and Launch) 52 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 53 Histogenics
Thank you for participating today. A copy of this presentation will be added to our website shortly. If you have additional questions, please email investorrelations@histogenics.com 54 Histogenics
References & Supporting Information 1. D Crawford MD, PhD, RJ Williams III, MD, TM DeBerardino MD - NeoCart, an Autologous Cartilage Tissue Implant, Compared to Microfracture for Treatment of Distal Femoral Cartilage Lesions. An FDA Phase 2 Prospective, Randomized Clinical Trial after twoYears.J Bone Joint SurgAm. 012;94:979-89. 2. D Crawford MD, PhD, DE Anderson, PhD, RJ. Williams III, MD, TM DeBerardino, MD, DC Taylor, MD, CB Ma, MD, and M Kane, MS - Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries, American Journal of Sports Medicine AJSM Vol. 45, No. 4, p 875-883 3.DC Crawford MD, PhD, CM Heveran, WD Cannon Jr, MD, LF Foo, MD, and HG P, MD -An Autologous Cartilage Tissue Implant NeoCart for Treatment of Grade III Chondral Injury to the Distal Femur Prospective Clinical Safety Trial at 2 Years 4.Maturation of Human Tissue Engineered Constructs Improves GAG Content and Fibrous Matrix Stability - JM Middendorf, S Shortkroff, C Dugopolski, S Kennedy, J Siemiatkoski, L Bartell, I Cohen, LJ Bonassar. 5.Mechanical Characterization of Autologous Chondrocyte Seeded Matrix Grafts After In Vitro Growth - JM Middendorf, D Griffin, S Kennedy, S Shortkroff, C Dugopolski, J Siemiatkoski, L Bartell, I Cohen, LJ Bonassar 55 Histogenics