InVivo Therapeutics. Developing Innovative Products for Spinal Cord Injury

Transcription

1 Developing Innovative Products for Spinal Cord Injury 1

2 Forward-Looking Statements Before we begin, we would like to remind everyone that during our presentation, we will be making forward-looking statements about our business, plans, and objectives. These statements are based on how we see things today. These statements can be identified by words such as believes, estimates, expects, or similar references to the future, and include statements we may make regarding our product development strategy, business prospects, and operational milestones. We wish to caution you that actual events or results may differ materially from those expressed in forward-looking statements made by us or on our behalf. For more information on the many factors that can result in actual performance differing from our forward-looking statements, please see our filings made with the SEC, including our 2014 Annual Report on Form 10-K filed on March 11, 2015 and our Quarterly Report on Form 10-Q filed on May 7,

3 Company Overview Publicly traded company (NVIV) based in Cambridge, MA Dedicated solely to developing effective therapies for spinal cord injury (SCI) Co-founded by Dr. Bob Langer in 2005 with focus on innovative biomaterials for treating spinal cord injury (SCI) Development programs in acute and chronic SCI Acute SCI: Neuro-Spinal Scaffold being investigated in a first-in-human clinical trial Chronic SCI: Neural stem cells with biomaterial delivery system (Bioengineered Neural Tissue) in development World-class advisory team including Robert Langer, Sc.D. (co-founder, SAB): holds largest number of medical patents with >1,050 patents issued and pending worldwide Richard Roberts, Ph.D. (BOD, SAB): Nobel Laureate in medicine & physiology V. Reggie Edgerton, Ph.D. (SAB): author of recent (April 2014) Brain article showing recovery of motor function in paraplegic patients after electrostimulation James Guest, M.D., Ph.D. (SAB): professor of neurosurgery pioneering spinal cord cell transplantation for the treatment of paralysis 3

4 Financial Information Trading Symbol NVIV Stock Price 1 $16.00 Exchange NASDAQ Market Cap 1 $ M Primary Shares Outstanding 26.6 M Fully Diluted Shares 30.7 M Avg. Daily Trading Volume (3 mo) 1 274,622 Cash on Hand at 3/31/2015 $24.5 M Financing in May 2014 resulted in net proceeds of $14.6 M Financing in Jan 2015 resulted in net proceeds of $11.0 M Q warrant exercises resulted in net proceeds of $2.6 M Monthly cash burn of about $1.1 M 1 As of 6/15/2015 4

5 Recent Accomplishments 1. Hired experienced leadership team 2. Raised cash to fund trial and operations 3. Accelerated pilot study timeline 4. Implanted 3 of the planned 5 patients with Neuro-Spinal Scaffold in the ongoing pilot study 5. Announced promising results for first two patients 6. Strengthened intellectual property portfolio 7. Significantly increased publications and presentations at scientific meetings 8. Uplisted to NASDAQ 5

6 Experienced Leadership Team Mark Perrin Chief Executive Officer Lorianne Masuoka, MD Chief Medical Officer Tom Ulich, MD Chief Scientific Officer Steven McAllister Chief Financial Officer Tamara Joseph, JD SVP, General Counsel & Chief Compliance Officer Kristin Neff VP, Clinical Operations & Project Management William D Agostino SVP, Operations Christopher McNulty VP, Business Development & Investor Relations Lisa Crockett VP, Regulatory Affairs & Reimbursement Planning 6

7 Spinal Cord Injury Common Spinal Cord Injury Causes of Spinal Cord Injury 1 Fractured Vertebral Body Spinal Cord Injury 9.2% 11.4% Automobile Falls 36.5% Violence 14.3% Sports 28.5% Other/unknown 1. Spinal cord injury facts and figures at a glance; Feb National Spinal Cord Injury Statistical Center. 7

8 Spinal Cord Injury: A Huge Unmet Clinical Need No products today treat SCI Drugs or stem cells alone show no clinical benefit Large patient population: 12,000 new cases of acute SCI per year in US 1 273,000 currently live with chronic SCI in US 1 Only small percentage of patients ever regain function 2 Direct cost of spinal cord injury Cost of care for the first year post-sci: $340K - $1.0M+ 1 Net present value of a quadriplegic injured at 25 for life: $4.6M Spinal cord injury facts and figures at a glance; Feb 2013; National Spinal Cord Injury Statistical Center. 2. 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). 8

9 The Neuro-Spinal Scaffold Value Proposition To redefine the life of the SCI patient Motor recover muscle control, movement, strength Sensory decrease neuropathic pain; avoid bed sores Autonomic recover bowel/bladder control and sexual function 9

10 Neuro-Spinal Scaffold for Acute SCI Designed to Promote Healing in Spinal Cord Injury 10

11 Neuro-Spinal Scaffold An Innovative Design Highly porous biopolymer Neuro-Spinal Scaffold magnified under scanning electron microscope Exclusive worldwide license from MIT & Boston Children s Hospital 11

12 The Neuro-Spinal Scaffold Is a Cellular Bandage PLGA is the inert biodegradable skeleton along which cells grow Poly-L-Lysine promotes cellular adhesion Cell Poly-Lysine PLGA Neuro-Spinal Scaffold promotes 3D appositional healing, similar to a suture or butterfly bandage Suture Butterfly Bandage Neuro-Spinal Scaffold 2D Wound Healing Internal 3D Wound Healing 12

13 The Founding Experiment: Neuro-Spinal Scaffold Alone And With Cells Provides a Functional Benefit Rat Hemisection Model scaffold plus cells (n = 13) scaffold alone (n = 11) lesion control (n = 12) cells alone(n = 12) The BBB score is widely used to test hindlimb motor function in rat SCI models Score ranges between 0-21; 0 = no function, 21 = full function Teng, Yang D., et al. PNAS (2002) 13

14 Primate Hemisection SCI Model Primate Injury Model Hemisection Winner of 2011 Apple Award granted by American Spinal Injury Association for the best published paper in the SCI rehabilitation literature Pritchard CD et al. Neuroscience Methods (2010) 14

15 Remodeled tissue volume (mm 3 ) Neuro-Spinal Scaffold Increases Functional Tissue Volume by Appositional Healing * Remodeled tissue by appositional healing 0 Control Scaffold Cross-sections from area of hemisection injury in control and Neuro-Spinal Scaffold implanted primates at 12 weeks after injury, manuscript in preparation 15

16 Neuropermissive Neuro-Spinal Scaffold Supports Creation of Detour Circuits By Collateral Sprouting Myelin Basic Protein (MBP) stained axons in remodeled tissue MBP positive fibers appear as dots (in cross section) and fibers (arrows) Sprouting, manuscript in preparation 16

17 The Neuro-Spinal Scaffold Improved Functional Recovery in Primates Kinematics score 4 Normal gait score 0 (n=8) -4-8 (n=6) (n=6) * -12 Control Scaffold Kinematics score is an objective, video-based composite of hindlimb stepping patterns that eliminates subjective observer scoring of gait. Based on results of primates with large (complete hemisection) lesions, manuscript in preparation 17

18 Progression of Acute SCI to Post-Traumatic Cysts in Rat Contusion Model Gray matter Normal 2 Hours after SCI 24 Hours after SCI White matter Acute hemorrhage Necrosis 1 week after SCI 4 Weeks after SCI 12 Weeks after SCI Microcystic degeneration Cystic cavitation Mature cystic cavity Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM. 18

19 Surgical Implantation of Neuro-Spinal Scaffold at 24hrs A window of opportunity exists when the white matter is still viable and can be preserved Irrigation Pipette Neuro-Spinal Scaffold Midline Dorsal Pial Incision & Gentle Irrigation Placement of Neuro-Spinal Scaffold Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM. 19

20 Neuro-Spinal Scaffold Preserves White Matter and Prevents Cyst Formation in Rat Contusion Model Control Scaffold-Treated Cyst Spared White Matter Remodeled Tissue Serial spinal cord sections at 3 months from 1 representative rat per group Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM. 20

21 Neuro-Spinal Scaffold Preserves Spinal Cord Architecture in Rat Contusion Model Control Scaffold Cavity Volume (mm 3 ) Cyst Reduction White Matter Sparing Remodeled Tissue Control * Scaffold White Matter Width (mm) 0.6 * Control Scaffold Remodeled Tissue Volume (mm 3 ) Control * Scaffold *P<0.05 Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM. 21

22 Spinal Cord Tissue Pressure (mm Hg) Neuro-Spinal Scaffold Implantation Returns Tissue Pressure to Normal Levels SCI in the Pig Model Increased spinal cord tissue pressure following injury leads to secondary damage including ischemia Neuro-Spinal Scaffold implantation procedure reduces elevated spinal cord tissue pressure Decreasing spinal cord tissue pressure may enhance: Spinal cord blood flow 2, which has been correlated to enhanced Tissue oxygenation 3 Scaffold Implantation in a Porcine Acute Spinal Cord Contusion Injury 1 Neurological recovery 3 1. Guest et al. manuscript submitted 2. Werndle et al. Neurological Crit. Care (2014) 3. Ducker et al. Surg. Neurol. (1978) 22

23 Neuro-Spinal Scaffold for Acute SCI Clinical Translation 23

24 HUD Designation Allows for HDE Approval Based on Probable Benefit Received Humanitarian Use Device (HUD) designation (April 2013) Indicated population must be fewer than 4,000 patients in the US InVivo HUD: patients with complete, non-penetrating thoracic and cervical SCIs Simpler path to approval (safety and probable benefit) through humanitarian device exemption (HDE) Probable benefit The device will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from the use of the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. -FD&C Act Section 520(m) 24

25 Neuro-Spinal Scaffold Pilot Study Underway Open-label study in 5 acute thoracic (T3-T12/L1), AIS A SCI patients 3 of 5 patients enrolled and in follow up Primary objective: safety and feasibility Secondary objective: preliminary evidence of effectiveness Improvement of ASIA Impairment Scale, sensory scores, motor scores, bladder and bowel function, the Spinal Cord Independence Measure (SCIM III) and MRI measures Frequent safety and effectiveness assessments 24, 48, 72 hours; 1 week; acute care discharge; 1, 2, 3, 6, and 12 months 25

26 Clinical Sites approved for up to 20 Barnes-Jewish Hospital at Washington University Medical Center (Dr. P. Santiago) Barrow Neurological Institute (Dr. N. Theodore) Site of first patient implantation Carolina Neurosurgery & Spine Associates (Dr. D. Coric & Dr. B. Bockenek) Site of second and third patient implantation Goodman Campbell Brain and Spine / Indiana University Neuroscience Center (Dr. E. Horn) Keck Hospital of University of Southern California (Dr. P Hsieh) Medical College of Wisconsin (Dr. S. Kurpad) Oregon Health & Science University (Dr. A. Raslan) University of Arizona Medical Center (Dr. T. Dumont ) University of California, Davis (Dr. K. Kim) University of Kansas Medical Center (Dr. P Arnold) University of Pittsburgh Medical Center Presbyterian (Dr. D. Okonkwo) 26

27 Expedited Enrollment of Pilot Trial FDA had originally required staggered enrollment: implant and follow each patient for 3 months before re-opening enrollment In December 2014, InVivo announced an accelerated timeline for the pilot trial Two months of safety data to be submitted to FDA for the first patient before reopening enrollment (enrollment reopened on Jan 8, 2014) One month of safety data to be submitted to FDA for the second patient before reopening enrollment for patients 3-5 (enrollment reopened March 26, 2015) No additional enrollment holds allowing for concurrent enrollment of patients 3-5 We anticipate full enrollment of 5 patients in

28 Functional Improvement in First Patient Implanted with Neuro-Spinal Scaffold Prior to surgery, the patient was assessed to have a complete AIS A injury at T11/T12 with no motor or sensory function below the level of injury At the 1-month assessment, the patient progressed from AIS A to AIS C Less than 5 % of AIS A patients with a T10-T12 injury progress to AIS C or D at one month 1 At the patient s 3-month assessment motor, sensory, bowel and bladder function were all improved from pre-surgery levels with no serious adverse events ASIA Impairment Scale (AIS): progressed from AIS A to AIS C Motor: return of active movement of the hip flexors against gravity (allowing for leg to chest motions) and palpable contractions of the knee extensors Sensory: return of sensation to two dermatomes extending down the top of the patient s legs and the S4-S5 dermatome Bowel & Bladder: regained bowel function and improved bladder function At the patient s 6-month assessment, motor function continued to improve at the knees I am very pleased with the first patient s progress since the scaffold was implanted. In my experience, this degree of sensory and motor improvement is unexpected. However, this is only one patient and we do not want to over-interpret the data. Dr. Nicholas Theodore, Director, Neurosurgery Spine Program, Barrow Neurological Institute 1 Zariffa, J., et al. "Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury." Spinal Cord 49.3 (2010): ASIA = American Spinal Injury Association; AIS = ASIA Impairment Scale 28

29 Additional Patients Enrolled in 2015 Patient 2 Prior to surgery, the patient was assessed to have a complete AIS A injury with no motor or sensory function below the level of injury At the 3 month exam, the patient remained classified as AIS A There was appreciable improvement in the second patient s trunk stability, selfcare, mobility and bowel and bladder function at the three-month post-implant assessment Patient 3 Prior to surgery, the patient was assessed to have a complete AIS A injury with no motor or sensory function below the level of injury. This patient is awaiting further assessment Both patients 2 and 3 were implanted by Dr. Dom Coric of the Carolina Neurosurgery and Spine Associates and Chief of Neurosurgery at Carolinas Medical Center 29

30 Potential Pivotal Probable Benefit Study Endpoints Change in AIS category* Motor recovery* Sensory recovery* Neurologic level change* Bowel/bladder function improvement* Pain decrease (major patient complaint) Quality of Life improvement (everyday living outcomes) * Patient #1 demonstrated improvement in these endpoints at 3 months 30

31 Pivotal Probable Benefit Study Plan Pilot Study Pivotal Probable Benefit Study For HDE approval, sponsor to show safety and probable benefit Historical/registry controls can be used for HDE approval Reduces number of patients required by up to half Endpoints and trial size will be informed by pilot study, new preclinical results, discussions with thought leaders, and communications with FDA Assuming continued positive results, potential to complete pivotal probable benefit study in 2017 with a small number of patients (pending discussions with FDA) 31

32 Future Clinical Development Strategy New Clinical Programs in Expanded Populations Acute Cervical Spinal Cord Injuries Humanitarian Use Device designation obtained for this population Enables InVivo to pursue rapid, streamlined program via HDE approval Premarket Approval (PMA) path Ability to expand to entire acute SCI population» Thoracic complete SCI» Cervical complete SCI» Cervical and thoracic incomplete SCI Expedited Access Pathway (EAP) may be an option for devices to treat SCI Ex-US Programs Clinical / regulatory strategies under review Will explore corporate partnerships for ex-us development and commercialization 32

33 Bioengineered Neural Tissue for Chronic SCI Designed to Improve Therapeutic Efficacy of Neural Stem Cell Transplant 33

34 Chronic Spinal Cord Injury: An Enormous Unmet Clinical Need Transforming Neural Stem Cell Transplant to Implanting Bioengineered Neural Tissue 273,000 currently live with SCI in US 1 Therapeutic options are limited Neural stem cell transplantation offers therapeutic promise Human GMP neural stem cells are now available 1. Spinal cord injury facts and figures at a glance; Feb 2013; National Spinal Cord Injury Statistical Center. 34

35 The Importance of a Physical Substrate 35

36 Neuro-Spinal Scaffold Promotes Neural Cell Attachment and Sprouting of Neurites Rat Neural Cells on Neuro-Spinal Scaffold with Neurite Sprouting Rat NSCs on Neuro-Spinal Scaffold with Neurite Sprouting Neural Cells Neurons, unpublished 36

37 Bioengineered Neural Tissue Using Surgically Implantable Scaffolds Proprietary biomaterials are being evaluated for neural stem cell transplantation into chronically injured spinal cord Neurons (MAP2) & Astrocytes (GFAP) 37

38 Surgical Removal of Glial Scar Glial Scar Tissue Resection Line (1) Resect margins of glial scar (2) Implant Bioengineered Neural Tissue into surgically created cavity 38

39 Bioengineered Neural Tissue Using Minimally Invasive Injectable Scaffolds Proprietary biomaterials are being evaluated for neural stem cell transplantation into chronically injured spinal cord Human NSCs in Injectable Scaffold Neurite Outgrowth Growth Matrix 39

40 Bioengineered Neural Tissue May Promote Bridging of the Injury Site Injury + Normal Injured Bioengineered Neural Tissue Repaired Neural Stem Cells Muscle Muscle Muscle Muscle Neural stem cells can create synaptic junctions with interneurons, sensory neurons, and motoneurons to functionally bridge the site of injury 40

41 Bioengineered Neural Tissue Promotes Functional Recovery BBB Score Mouse Neural Stem Cells in Rat Hemi-Section Model Human Neural Stem Cells (hnscs) in Rat Hemi-Section Model Scaffold + highdose hnscs Scaffold + lowdose hnscs Scaffold alone Lesion control hnscs alone 3 Teng, Yang D., et al. Proceedings of the National Academy of Sciences (2002) Weeks post injury US Patent: 8,858,966 (licensed by InVivo) Stem cells and scaffold demonstrate synergistic benefits 41

42 Next Steps for Bioengineered Neural Tissue Optimize Cell Attachment Biomaterial Scaffold Development Optimize Chemical Composition Optimize Scaffold Geometry Method of Scaffold Cell Seeding Neural Stem Cell Development Cell Attachment to Scaffold In Vitro Cell Differentiation Biocompatibility of Scaffold Method of Scaffold Implantation Preclinical Animal Model Development Cell Survival and Differentiation Safety and Efficacy Quantify Cell Viability in vivo Characterize Cell Phenotype in vivo InVivo plans to partner with a stem cell company to accelerate project timelines 42

43 Neuro-Spinal Scaffold Commercial Opportunity, IP and Summary 43

44 Neuro-Spinal Scaffold Commercial Opportunity Cost of spinal cord injury Cost of care for the first year post-sci: $340 k - $1.0 M+ 1 Net present value to maintain a quadriplegic injured at 25 for life: $4.6 M+ 1 US commercial opportunity Majority of acute SCIs treated in Level I trauma centers (203 in US) Feasible to become a commercial organization with a small direct sales force Spinal Cord Injury Type US Incidence/ Prevalence 1,2 US TAM 2 Complete (AIS A); non-penetrating 3 3,750/yr $200 - $600 M/yr All acute SCI 12,000/yr $600 M - $1.8 B/yr Chronic SCI 273,000 $>10 B glance; Feb 2013; National Spinal Cord 1. Spinal cord injury facts and figures at a Injury Statistical Center. 2. Company estimates 3. Subset of SCI patients in HUD application 44

45 Intellectual Property Core technology licensed from MIT and Boston Children s Hospital Broad US composition and methods patent recently issued covering Neuro-Spinal Scaffold and Neuro-Spinal Scaffold + stem cells (Patent number: 8,858,966, expires 2027) Co-inventors: Drs. Robert Langer, Rajiv Saigal, and Yang Teng Additional patents and applications held by InVivo only Packaging, Instrumentation and Manufacturing patents are pending Additional intellectual property being pursued for Bioengineered Neural Tissue 45

46 Increased Publications and Presentations at Major Scientific Meetings Previous presentations 83 rd American Association of Neurological Surgeons (AANS) Annual Scientific Meeting James Guest, M.D., Ph.D et al., presented Reduction of Intraparenchymal Pressure after Porcine Acute Spinal Cord Contusion Injury by Neuro-Spinal Scaffold Implantation Alexander Ropper, M.D. et al., presented First Human Implantation of a Polymer Scaffold for Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility Upcoming presentations 2015 New England Neurosurgical Society Annual Meeting (NENS) 2015 Annual Symposium of the National Neurotrauma Society (NNS) 2015 Annual Meeting of the Congress of Neurological Surgeons (CNS) Numerous publications in process 46

47 Summary Recent achievements First-in-human Neuro-Spinal Scaffold trial initiated First patient implanted in mid-october; 6-month data reported on May 14 Second patient implanted in mid-january; 3-month data reported on May 14 Third patient implanted in early June Accelerated pilot trial timeline with FDA Strengthened senior leadership team Raised $28.2M (net) in two financings and warrant exercises Granted US patent covering Neuro-Spinal Scaffold and Neuro-Spinal Scaffold + stem cells Increased publications and presentations at major scientific meetings Upcoming anticipated milestones Enroll all 5 patients in Pilot Study in 2015 Provide clinical updates as appropriate Initiate Pivotal Probable Benefit Study in