InVivo Therapeutics Investor · PDF file · 2018-01-03CONTEMPO Registry Study, ......

1InVivo Therapeutics

InVivo TherapeuticsInvestor PresentationDeveloping Innovative Products for Spinal Cord Injury Updated: January 3, 2018


Forward-Looking Statements

Before we begin, we would like to remind everyone that any statements in this presentation about futureexpectations, plans and prospects for InVivo Therapeutics Holdings Corp. (the “Company”) , including statementsregarding the safety and effectiveness of the Neuro-Spinal Scaffold™, the Company’s proposal for a randomizedcontrolled trial, the expected timing of providing clarity on a clinical path forward, the establishment of the Neuro-Spinal Scaffold™ as the first and foundation of spinal cord injury (“SCI”) treatments, the number of patients in theCONTEMPO Registry Study, the status of the clinical program, and other statements containing the words“believes,” “anticipates,” “targets,” “plans,” “expects,” and similar expressions, constitute forward-lookingstatements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differmaterially from those indicated by such forward-looking statements as a result of various important factors,including risks and uncertainties relating to the Company’s ability to initiate, conduct and complete clinical trials;the Company’s ability to submit an HDE application and receive regulatory approval for the Neuro-Spinal Scaffold;the impact of achieving the Objective Performance Criterion on the U.S. Food and Drug Administration (the “FDA”)approval process; the Company’s ability to commercialize its products; the Company’s ability to develop, marketand sell products based on its technology; the expected benefits and efficacy of the Company’s products andtechnology in connection with the treatment of spinal cord injuries; the availability of substantial additional fundingfor the Company to continue its operations and to conduct research and development, clinical studies and futureproduct commercialization and other factors discussed in the “Risk Factors” section of our most recent quarterlyreport on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) and in the Company’s otherfilings from time to time with the SEC. In addition, the forward-looking statements included in this presentationrepresent the Company’s views as of the date hereof and should not be relied upon as representing the Company’sviews as of any date subsequent to the date hereof. The Company anticipates that subsequent events anddevelopments will cause the Company’s views to change. However, while the Company may elect to update theseforward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.


InVivo – Pioneering Spinal Cord Injury Therapies

• Neuro-Spinal Scaffold™: an Investigational Product for Acute Spinal Cord Injury (SCI)

• Acute SCI: Total Estimated Available US Market of $400 million to $1.2 billion– No effective treatments available for SCI– No direct competitive products in clinical development

• Humanitarian Device Exemption (HDE) regulatory pathway

• Encouraging data from INSPIRE study of Neuro-Spinal Scaffold in Thoracic SCI– 7 of 16 (43.8%) study patients who have reached the six-month primary endpoint have

regained some neurologic function versus the Objective Performance Criterion (study success definition) of 25%

– INSPIRE enrollment on hold since July 2017 following three patient deaths

• InVivo is in ongoing discussions with the FDA and has proposed a randomized controlled trial to supplement the existing clinical evidence for the Neuro-Spinal Scaffold

• World-class Scientific Advisory Board (SAB)– Robert Langer, Sc.D. (cofounder) : 1,000+ patents worldwide– Richard Roberts, Ph.D. : Nobel Laureate in medicine & physiology– V. Reggie Edgerton, Ph.D. : Pioneer of electrostimulation for rehabilitation– James Guest, M.D., Ph.D. : Neurosurgeon & stem cell expert


Financial Information

1 NASDAQ closing price on 1/2/182 As of 10/28/173 As of 9/30/17; Including the following potentially dilutive securities: warrants, unvested restricted stock units and stock options

Trading Symbol NVIVStock Price1 $0.91Exchange Nasdaq Global MarketMarket Cap1 $31.1 MPrimary Shares Outstanding2 34.2 MFully Diluted Shares3 41.2 MAvg. Daily Trading Volume (3 mo)1 203,666Cash, Cash Equivalents and Marketable Securities on Hand3 $17.2 M


Spinal Cord Injury: An Unmet Clinical Need with No Effective Treatments

• Unserved patient population with no options– Approximately 15,000 new cases of acute SCI per year in US1

– Patients affected by loss of motor, sensory and autonomic (bowel, bladder and sexual) function

– Only small percentage of patients ever regain function3

– Approximately 282,000 currently live with chronic SCI in US2

Chronic SCI: >6 months after injury

• Direct cost of spinal cord injury– Cost of care for the first year post-SCI: $340K - $1.0M+2

– Net present value of the cost for a quadriplegic injured at 25 for life: $4.6M+2

1. Company estimate derived from: Selvarajah et al., J. Neurotrauma (2014), Jain et al., JAMA (2015), Saunders et al., Top Spinal Cord Inj. Rehabil. (2015)2. National Spinal Cord Injury Statistical Center, Facts and Figures at a Glance. Birmingham, AL: University of Alabama at Birmingham, 2016.3. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power

needed for therapeutic clinical trials. Spinal cord (2007).

We seek to establish the Neuro-Spinal Scaffold as the foundation of the standard of care for acute SCI


Spinal Cord Injury Patient DistributionAIS A is the Largest Patient Segment

15,000 Acute SCIs per year1

Cervical9,200

Thoracic3,600

Lumbar2,200

A3,400

B1,200

B300

C400

Cervical

A2,400

Thoracic

Lumbar

D500

C1,200

D3,400

*Assumes equal distribution among all ages & does not take into consideration INSPIRE inclusion/exclusion criteria

1. Company estimate derived from: Selvarajah et al., J. Neurotrauma (2014), Jain et al., JAMA (2015), Saunders et al., Top Spinal Cord Inj. Rehabil. (2015)Other projections based on company estimates

INSPIRE Study

American Spinal Injury Association Impairment Scale (AIS)

Grade Description (Abridged)

A Complete – No motor or sensory function preserved in sacral segments (S4-5)

BSensory Incomplete – Sensory but not

motor function preserved below level of injury and includes sacral segments

C

Motor Incomplete – Motor function preserved below level of injury; voluntary

anal contraction OR sparing of motor function 3 levels below injury

DMotor Incomplete – Similar to AIS C but with at least half of key muscles below

injury functioning against gravityE Normal

= Expansion Opportunities


Neuro-Spinal Scaffold™ for Acute SCIDesigned to Promote Healing inSpinal Cord Injury


Evolution of Acute Management of Spinal Cord Injury

• Non-surgical management: Traction and bedrest (prevent additional trauma)

• Surgical management: Bony decompression and spinal column alignment/stabilization – Minimize secondary injury and provide

support to the spine– Standard of care has transitioned to early

decompressive surgery (<24-48 hours post-injury) in attempts to remove ongoing spinal cord compression

Despite significant advances in surgical repair to the spinal column, modern day acute management of SCI does not address repair of the spinal cord


InVivo’s Pioneering Clinical Approach for Acute SCI: The Neuro-Spinal Scaffold™

• Proprietary, highly porous biopolymer Neuro-Spinal Scaffold• Composition:

– PLGA is the biodegradable skeleton along which cells can grow– Poly-L-Lysine promotes cellular adhesion

Company images


Progression of Acute SCI to Post-Traumatic Cavityin Contusion Injuries

Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM.

Spinal CordInjury

Hemorrhage&

Spinal Cord Swelling

Reduced Blood Flow

&Ischemic Necrosis

CavityDevelopment

&White Matter

Reduction

Chronic injury and mature

cavity formation

Time

White matter

Highly vascularized gray matter

Acute hemorrhage & necrosis Mature cavityLiquefactive necrosis

Normal 2 hours after SCI 24 hours after SCI 12 weeks after SCI

Histology from rat contusion model of SCI


First Neuro-Spinal Scaffold™ Implantation in Human Contusion Injury


Neuro-Spinal Scaffold™ Mechanism of Action

• Preservation of white matter and reduction of cyst formation via appositional healing (i.e., spinal cord architecture)

• Neural regeneration through the formation of neuro-permissive remodeled tissue

• Remyelination of segmentally demyelinated white matter axons by Schwann cells

Internal 3D Wound Healing

Butterfly Bandage Neuro-Spinal Scaffold

2D Wound Healing


The Neuro-Spinal Scaffold™ Preserves Macroscopic Spinal Cord Architecture

Control Scaffold

*P<0.05

Rem

odel

ed T

issu

eVo

lum

e (m

m3 )

Control Scaffold0.0

0.5

1.0

1.5

2.0 *

Cav

ity V

olum

e (m

m3 )

Control Scaffold0

2

4

6

*

Whi

te M

atte

r W

idth

(mm

)

Control Scaffold0.0

0.2

0.4

0.6 *Cyst Reduction White Matter Sparing Remodeled Tissue

Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM.

Rat Acute Spinal Cord Contusion Injury (at 12 weeks)Neuro-Spinal ScaffoldControl

Cyst

Neuro-Spinal Scaffold




The Neuro Spinal Scaffold™ Increases Remodeled Tissue Supporting Neural Regeneration


Remodeled tissue with extensive neuro-permissive matrix

Neuro-permissive matrix supports neural regeneration

Control

Minimal neuro-permissive matrix

Company images

Rat Acute Spinal Cord Contusion Injury (at 12 weeks)


Neural Regeneration and Remyelination with Schwann Cells after Neuro-Spinal Scaffold™Implantation

Schwann Cells restore signal transduction

Oligodendrocytes Schwann Cells

Contusion Injury

Inset: Schwann cells ensheathing axons

White MatterEpicenterSchwann Cells aid neural

regenerationCentral epicenter (a) and

white matter (b)

Rat Acute Spinal Cord Contusion Injury (at 12 weeks)


Encouraging Data in Two Major Types of Spinal Cord Injury

Closed (Contusion) Injury

• Outer region of cord is preserved and cord appears intact externally

• Injury leads to cavity filled with necrotic material

• Pressure builds inside the cord, which may lead to further injury

• Preclinical model: contusion injury

Open (Compound) Injury

• Outer region of cord is breached and injury is visible externally

• Myelotomy (cutting into the cord) may not be required

• Minimal added pressure inside cord• Preclinical model: hemicordectomy

Cavity Cavity

Laceration/Maceration

Layer RT et al. Neurosurgery. Manuscript accepted.


Neuro-Spinal Scaffold™ Promotes Neural Regeneration and Functional Recovery

Increased remodeled tissue

Slotkin JR et al. Biomaterials. In press.

Neural regenerationMyelin basic protein stained

axons in remodeled tissue

Improved functional recovery

Primate Hemicordectomy Model (at 3 Months)


Hemicordectomy Model

*P<0.05


Neuro-Spinal Scaffold™ for Acute SCIClinical & Regulatory Development Plans


Humanitarian Device Exemption (HDE):A Lower Approval Threshold

• Provides less burdensome regulatory process– Lower approval threshold: demonstrate safety and probable benefit (rather

than effectiveness)

• Probable benefit: a classic risk/benefit analysis– Device does not expose patients to an unreasonable or significant risk– Probable benefit to health from the use of the device outweighs the risk

• In Dec 2016, 21st Century Cures Act increased ceiling of qualified patient population from 4,000 to 8,000 patients per year– InVivo’s initial Humanitarian Use Device population: thoracic and cervical SCI

patients with complete paralysis (AIS A)*– Cures Act may allow InVivo to take advantage of the HDE pathway for patients

with incomplete paralysis (AIS B and AIS C)* Would require applying for expanded HUD and conducting a separate study

– Cures Act also requires that FDA publish draft guidance that defines the criteria for establishing “probable benefit” by mid-2018

*Excludes penetrating injuries such as gunshot or knife injuries


The INSPIRE Study

• Clinical study in support of an HDE application– Primary endpoint: improvement in ASIA Impairment Scale (AIS) grade by 6 months– Additional endpoints: sensory and motor scores, bladder & bowel function, Spinal Cord

Independence Measure, pain, quality of life– Assessments at 1, 2, 3, 6 (primary), 12 and 24 months

• Objective Performance Criterion (study success definition) – at least 25% of patients improve AIS grade by 6 months

InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold™ for Safety and Neurologic Recovery in Subjects with Complete Thoracic AIS A Spinal Cord Injury


Clinical Path Forward

• Enrollment on hold following three patient deaths in INSPIRE

• Although InVivo and the respective site principal investigators do not believe these deaths were related to the Neuro-Spinal Scaffold™, the company is in communication with FDA to ensure that these cases have been comprehensively evaluated and to ensure all appropriate risk mitigations have been implemented

• As part of ongoing discussions with the FDA, InVivo has proposed a randomized controlled trial to supplement the existing clinical evidence for the Neuro-Spinal Scaffold

• InVivo does not expect to reopen enrollment in INSPIRE

• Expect to provide additional clarity on clinical path forward in Q2-2018


INSPIRE AIS Conversion Rate Versus Objective Performance Criterion

Published historical benchmarks for AIS conversion rates were used to establish the OPC

15.6% 15.5%

36.8%

43.8%

0%

10%

20%

30%

40%

50%

EMSCI(n=256, 6 months)

Model Systems(n=194, 12 months)

INSPIREAll Patients

(n=19, 6 months)

INSPIREEvaluable Patients(n=16, 6 months)

Complete (AIS A) Thoracic SCI AIS Conversions

1 Zariffa et al., Spinal Cord (2011); European Multicenter Study about Spinal Cord Injury (EMSCI)2 Lee et al., J. Spinal Cord Med (2014); Spinal Cord Injury Model System (US)3 Approval is not guaranteed if the OPC is met and HDE approval may still be obtained if OPC is not met if probable benefit outweighs the risk.

= 7/16 evaluable patients have converted at 6 months

OPC = study success3

(25%)

1 2

INSPIRE primary endpoint and OPC are based on evaluable patients at 6 months.


Neurologic Outcomes in Evaluable Patients to Date

Note: Three additional subjects died within two weeks of implantation.

Date of Implant Sex

Age (Pediatric ≤ 21 yoa)

Neurologic Level of Injury

Injury Type

Time to Implant

Neurologic Outcome at

Primary EndpointNeurologic Outcome to Date

Oct. 2014 M Adult T11 Closed 9 hrs. AIS C Remains AIS C at 24 monthsJan. 2015 F Adult T7 Open 46 hrs. AIS A Remains AIS A at 24 monthsJun. 2015 M Adult T4 Closed 83 hrs. AIS B Converted to AIS C at 24 monthsAug. 2015 M Adult T3 Closed 53 hrs. AIS A Remains AIS A at 24 monthsSept. 2015 F Pediatric T8 Open 69 hrs. AIS B AIS B at 6 months*Feb. 2016 M Pediatric T10 Open 9 hrs. AIS B Remains AIS B at 12 monthsMar. 2016 M Adult T3 Closed 21 hrs. AIS A Remains AIS A at 12 monthsMay 2016 M Adult T4 Closed 40 hrs. AIS B Converted to AIS C at 12 monthsNov. 2016 M Adult T8 Open 38 hrs. AIS A Remains AIS A at 12 monthsDec. 2016 M Pediatric T10 Open 22 hrs. AIS A Remains AIS A at 12 monthsJan. 2017 M Adult T12 Closed 68 hrs. AIS B AIS B at 6 monthsMar. 2017 M Adult T2 Closed 80 hrs. AIS A AIS A at 6 monthsMar. 2017 F Adult T9 Open 30 hrs. AIS A AIS A at 6 monthsApr. 2017 M Adult T4 Closed 47 hrs. AIS A AIS A at 6 monthsMay 2017 M Adult T9 Closed 77 hrs. AIS A AIS A at 6 monthsJun. 2017 F Adult T6 Closed 21 hrs. AIS C AIS C at 6 months

* Patient lost to follow-up after primary endpoint visit


Motor Improvements in Patients with Low Thoracic Injuries (T11-T12)

02468

101214161820

0 3 6 9 12

LEM

S

Months Post-Injury

First Patient (T11)

Recent Patient (T12)Palpable hip contractions

• First patient (implanted October 2014) improved from T11 complete AIS A to AIS C at 1 month

– Continued motor improvement from months 6 to 12

• Patient implanted Jan 2017 demonstrated motor improvement and improved from T12 complete AIS A to AIS B at 6 months

Hip movement & palpable knee contractions

Knee movement

Palpable ankle contractions

Lower Extremity Motor Score (LEMS)*

Hip move-ment

Knee move-ment

*Note: assessments of ankle muscles were not made on the Recent Patient (T12) at 0 and 1 months due to immobilization; these muscles scored 0 at 2 months

Improved knee movement


Contemporary Thoracic SCI Registry Study (“CONTEMPO Registry Study”)

• InVivo plans to complement Neuro-Spinal Scaffold™ clinical studies with the CONTEMPO Registry Study

• A comprehensive evaluation of the recent natural history of acute, complete thoracic SCI patients– Christopher & Dana Reeve Foundation North American Clinical Trials Network

(NACTN) Registry– Plan to utilize additional existing registries (e.g., Model Systems, EMSCI)– Match patient characteristics to INSPIRE (to the extent possible)– Evaluate only patients injured since 2006

• CONTEMPO Registry Study designed to provide contemporary benchmarks for INSPIRE

• Estimated number of patients in CONTEMPO Registry Study: 100-200


Neuro-Spinal Scaffold™ Commercial Opportunities

• Commercial Strategy– Establish InVivo commercial organization– Targeted relationship development with Level I/II trauma centers, neurosurgeons and payers– Leverage clinical data and KOL support to become foundation of Standard of Care

• Reimbursement Strategy– Assist providers in achieving favorable coverage and payment so that reimbursement is not

a deterrent to appropriate patient access– Advocate for a specific CPT code (procedure payment for neurosurgeons), new technology

add-on payments, and clinical guideline inclusion based on outcomes and KOL support– Continue to leverage established payer advisory board (PAB)

1. Company estimates.2. Excludes penetrating injuries

Spinal Cord Injury Type US Incidence1 US Total Available Market1

Complete (AIS A) – Thoracic2 1,950 $100 - $300 M/yrComplete (AIS A) – Cervical2 2,750 $150 - $450 M/yrAIS A, B and C SCI – Thoracic & Cervical2 8,000 $400 M - $1.2 B/yr


Improved AIS Grade Leads to Reduced Lifetime Rehospitalization Costs

• Burden of Illness manuscript published: “Relationship of ASIA Impairment Scale (AIS) Grade to Post-Injury Hospitalization and Costs in Thoracic Spinal Cord Injury”1

• Net Present Value of Lifetime Hospitalization Costs:

1Dukes et al., Neurosurgery (2017)


Neuro-Spinal Scaffold™IP and Conclusions


Neuro-Spinal Scaffold™ Intellectual Property Portfolio

• Core technology covering the Neuro-Spinal Scaffold licensed from MIT and Boston Children’s Hospital

• US composition and methods patent 8,858,966 (expires 2027)– Covers composition of the Neuro-Spinal Scaffold– Japanese, Australia, Canada, and South Korea patents issued– European patent application in prosecution

• Broader US composition patent 9,101,695 (expires 2027)– Covers broad array of biodegradable and/or bioabsorbable polymeric implants – Japanese and Australia patents issued; others in prosecution

• Broader US methods patent 9,440,008 (expires 2027)– Covers methods of treatment of compression or contusion spinal cord injuries

with a broad array of biodegradable and/or bioabsorbable polymeric implants Includes the Neuro-Spinal Scaffold™

– Additional layer of protection against potential infringers


Observations from INSPIREand Upcoming Corporate Milestones

• Key INSPIRE Observations to Date– Demonstrated surgical feasibility of acute Neuro-Spinal Scaffold™

implantation– Reported AIS conversion rate that exceeds published natural history

rates and Objective Performance Criterion– Observed delayed conversions at 12 and 24 months– Seek to use learnings from INSPIRE to mitigate risk in proposed

randomized study

• Upcoming Corporate Milestones– InVivo is in ongoing discussions with the FDA and has proposed a

randomized controlled trial to supplement the existing clinical evidence for the Neuro-Spinal Scaffold

– Expect to be able to provide additional clarity on clinical path forward in Q2-2018

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