A Majority-Owned Subsidiary of Fortress Biotech

Transcription

1 A Majority-Owned Subsidiary of Fortress Biotech

2 Forward Looking Statements Statements in this presentation that are not descriptions of historical facts are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of We have attempted to identify forward-looking statements by terminology including anticipates, believes, can, continue, could, estimates, expects, intends, may, plans, potential, predicts, should, or will or the negative of these terms or other comparable terminology. Forward-looking statements are based on management s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are risks relating to: our growth strategy; results of research and development activities; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; the early stage of products under development; our need for substantial funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our parent company s SEC filings. We expressly disclaim any obligation or undertaking to update or revise any statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances after the date of this presentation.

3 Overview Novel Cellular Therapies for the Treatment of Severe Traumatic Brain Injury Based on Research from University of Texas Health Science Center (Houston) Two Technology Platforms, Most Clinically Advanced Programs for Severe TBI Current Gen (CEVA101): autologous mononuclear cells for severe TBI Adult TBI: Phase 1 in patients published, Stem Cells, 11/2016 Pro-Inflammatory Cytokines; Volumetric Preservation Pediatric TBI: Phase 1 in patients published, Pediatric Critical Care, 03/2016 Therapeutic Intensity; Volumetric Preservation Phase 2 Studies: ongoing, randomized, placebo-controlled in severe TBI Data as early as 1H2019 in Children, as early as 2H2019 in Adults Equivalent of Breakthrough Designation Granted (RMAT, Cures Act), 11/2016 Next Gen (CEVA102): autologous or allogeneic mechano-transduced cells Bioreactor device, cells for TBI and other indications (grant-funded) $Billion Markets with No Approved Therapy (same SOC for 30 years) $12M+ in NIH/DoD Grant Funding for Ongoing Studies

4 Fortress & Cellvation Leadership Fortress Biotech Management Lindsay A. Rosenwald, M.D. Executive Chairman Michael S. Weiss, J.D. Executive Vice Chairman 20+ years experience Life Sciences Entrepreneur and Investor 20+ years experience Life Sciences Entrepreneur and Investor Cellvation Management Lindsay A. Rosenwald, M.D. Co-Founder and Executive Chairman Frank Taffy, J.D. Co-Founder, President and Chief Executive Officer David J. Horin, C.P.A. Interim Chief Financial Officer Elizabeth Moore, M.S. Consultant Regulatory Affairs 20+ years experience Life Sciences Entrepreneur and Investor 15+ years experience Forest Labs: Former Head of Business Affairs 15+ years experience Chord Advisors: Managing Partner 30+ years experience Pfizer La Jolla: Former Head of Regulatory Affairs Cellvation Board of Directors Cellvation Scientific Advisory Board Charles S. Cox, Jr., M.D. Co-Founder and Chairman of Scientific Advisory Board Brijesh Billy Gill, M.D. Co-Founder and Key Scientific Advisor Additional SAB Members Appointments To Be Disclosed Soon Lindsay A. Rosenwald, M.D. Executive Chairman Michael S. Weiss, J.D. Director Frank Taffy, J.D. Director University of Texas Health Science Center Houston: Neuro-Trauma University of Texas Health Science Center Houston: Acute Care Surgery TBA

5 Development Pipeline CEVA 101 MNCs for Pediatric TBI CEVA 101 MNCs for Adult TBI CEVA 102 MT-MSCs for Pediatric TBI CEVA 102 MT-MSCs for Adult TBI CEVA-D Bioreactor (Device) Preclinical Phase 1 Phase 2 Phase 3 Ongoing, NIH-funded Ongoing, DoD-funded Pre-IND Pre-IND Device Pathway

6 Novel Therapies for Severe Traumatic Brain Injury Leading cause of death and major disability in US (~2M annually) 55% from traffic accidents, 20% from falls Categorized Based on Severity (Mild to Severe) Severe TBI: extended loss of consciousness, coma, hospitalization Incidence of Severe TBI in US Adults: ~200K annually Peds: ~50K annually (ORPHAN) Standard of Care No Approved Reparative Therapy Primary Injury Irreversible, Focus on Secondary Injury Control of Inter-Cranial Pressure (result of swelling, edema) Decompressive Craniectomy (if ICP cannot be controlled) Volumetric Loss Following Severe TBI 8-12% of white matter, gray matter, other regions Correlates with Functional Loss

7 CEVA 101: Phase 1 in Children (Completed) Autologous Bone Marrow Mononuclear Cell Therapy for Children with Severe TBI 10 patients treated with single-dose; time- & severity-matched controls Design: safety evaluation of bone marrow harvest, reinfusion of mononuclear cells Population: severe TBI in ages 5 to 14 years with post-resuscitation Glasgow of 5 to 8 Single Center: Children s Memorial Hermann Hospital, UTHealth-Houston Outcomes Safety: all patients survived; no harvest- or infusion-related SAEs Efficacy: no reduction in gray, white matter, CSF volumes 6-mos post-injury Published: Cox, Neurosurgery (2012); with new controls in Liao, Pediatric Critical Care (2015) Liao (2015): retrospective cohort design of Phase 1 patients vs. new controls Cell therapy significantly reduced therapeutic intensity (PILOT) Study Design Dosing Schedule Primary Endpoint Secondary Endpoint Phase 1 study in children with severe TBI (Completed, published in Neurosurgery, (2016) Single center 10 children aged 5-14 with severe TBI at single dose level 20 time- and severity- matched controls autologous BMMNCs/kg, administered intravenously within 48 hours after TBI Safety No harvest- or infusion-related SAEs Volumetric Preservation No reduction of gray, white matter, CSF 6-mos after injury

8 PILOT Score ICP (mmhg) CEVA 101 Phase 1: Reduced Therapeutic Intensity in Pediatric TBI Daily Pediatric Intensity Level of Therapy (PILOT) Average Maximum Daily ICP Values P< P<0.01 Cell Infusion p=0.001 p=0.03 Week 1 Week 2 Time Matched Controls Aggregate Controls Phase I Treated Admission Day

9 Brain Variable Volumes (in cm 3 ) Previous Studies: Volumetric Loss in Children with Severe TBI TBI vs. Normals: Volumetric Analysis P=0.065 TBI P=0.003 Typically Developing P=0.05 P=0.002 Mean Brain Volumes in TBI vs. Age-Matched Controls Progressive Atrophy Accentuated in Children Wilde EA, et al., J Neurotrauma, 2005

10 cmri Brain Variable Volume (ml) CEVA 101: Volumetric Preservation in Children with Severe TBI (Phase 1) P= P=0.94 P=0.39 P=0.83 Post-TBI MRI at Month 1 (Scan 1) vs. Month 6 (Scan 2) Preservation of Grey Matter (GM), White Matter (WM), Intracranial Volume (ICV)

11 CEVA 101: Phase 2 in Children with Severe TBI (Ongoing) Phase 2 (n=50): multi-center, double-blinded, randomized, placebo-controlled Population: children aged 5 to 17 with acute TBI from closed head trauma Controls to undergo sham harvest, infusion with placebo Infusion: within 48 hours of injury, two doses ( or BMMNCs/kg) Enrolling Sites UT Health Science Center (Houston) & Memorial Hermann: open since 08/2013 University of Arizona & Phoenix Children's Hospital: open since 08/2013 Status, Rate 39 of 50 enrolled as of 5/30/2018 (1 patient / six weeks) Completion by 1H2019 Funding: $4M+ from NIH Study Design Dosing Schedule Primary Endpoint Secondary Endpoint Phase 2 in children with severe TBI (Ongoing) Multi-center, randomized, doubleblinded, placebocontrolled study in 50 children (aged 5-17) with severe TBI from closed head trauma Single Infusion of one of two doses ( or BMMNCs/kg) OR placebo within 48 hours of injury Volumetric Preservation of Grey Matter, White Matter Reduction in Pro- Inflammatory Cytokines Reduced ICP / PILOT

12 CEVA 101: Phase 1/2 in Adults with Severe TBI (Completed) Autologous Bone Marrow Mononuclear Cells in Adult Patients with Severe TBI 25 Patients Total: 15 treated, time-/severity- matched controls Design: open label, nonrandomized trial to evaluate safety, feasibility and potential signal of treatment effect of IV infused BMMNCs at three dose levels Population: adults aged 15 to 55 years, post-resuscitation Glasgow of 5 to Single Center: University of Texas Health Science Center in Houston Outcomes Safety & Feasibility: safe, logistically feasible; no harvest- or infusion related SAEs Efficacy: reduction in pro-inflammatory cytokines (IL1, IFNγ, TNFα); volumetric preservation Preservation of brain volume (white matter, gray matter) 0 vs. 10% loss in controls (& previous 6-mos post-injury Published: Cox, Stem Cells (2016) Study Design Dosing Schedule Primary Endpoint Secondary Endpoint Phase 1/2 dose escalation study in patients (Completed, published in Stem Cells) Single center, nonrandomized in 15 adults with severe TBI at 3 dose cohorts and 10 timematched controls Three doses: ; ; autologous BMMNCs/kg, administered IV w/in 48 hours after TBI Safety Found to be safe and logistically feasible with no harvest-or infusion-related SAEs Reduction in Pro- Inflammatory Cytokines Volumetric Preservation

13 Brain Volume x x x x CEVA 101: Volumetric Preservation in Adults with Severe TBI (Phase 1) P=0.004 P=NS P=NS % volume loss % volume loss Acute 6 Month Acute 6 Month Controls Treated

14 CEVA 101: Phase 2 in Adults with Severe TBI (Ongoing) Phase 2 (n=55), randomized (3:2), blinded, placebo-controlled Population: adults aged 18 to 55 with acute TBI from closed head trauma Controls to undergo sham harvest and infusion with placebo Infusion: within 48 hours of injury, two doses ( or BMMNCs/kg) Enrolling Site(s): University of Texas at Health Science Center (Houston): open as of 11/2016 Vanderbilt University: open by 2H2018 (partially funded by donors) Status, Rate 14 of 55 enrolled at single site (UTH) as of 5/30/ patient per month (2 patients per month with Vanderbilt) Completion by 1H2020 (with addition of Vanderbilt) Funding: ~$12M+ from DOD Study Design Dosing Schedule Primary Endpoint Phase 2 in Adults with severe TBI (Ongoing) Randomized (3:2) blinded, placebocontrolled in 55 adults (ages 18-55) with acute severe TBI from closed head trauma Single Infusion of one of two doses ( or BMMNCs/kg) OR placebo w/in 48 hours of injury Volumetric Preservation of Grey Matter, White Matter Secondary Endpoint Reduction in Pro- Inflammatory Cytokines Reduction in ICP

15 Why Autologous vs. Allogenic? Autologous Cells: minimally manipulated but protected as 351 Biologic in US Based on Non-Homologous Use : other than biologic purpose of cells Japan: treated as Regenerative Medicine Product ; exclusivity, early access Process: bone marrow harvest followed by simple cell separation, infusion Business Model: Works in Acute Trauma Setting (TBI, Stroke) Invasiveness of bone marrow harvest not an issue (patients in coma) Bone marrow harvest by pathologist, surgeon (new devices simplify) Majority of major trauma centers affiliated with cell separation lab Point of Care cell separation devices now available (Cesca, BioCardia) Cost of Goods Substantially Lower than Allogeneic Cells CEVA101: ~$8K per course (lab separation); ~$5K per course (point of care) Allogeneic: based on Mesoblast JP pricing, MSCs for agvhd ~$30K COGS per dose / ~$100K cost per patient Equal or Better Safety, Efficacy Based on data in 60+ patients (pediatric, adult TBI; adult stroke) Compared to Athersys (NASDAQ:ATHX) MSCs in stroke

16 Protected as 351 Biologic in US Minimally-Manipulated Autologous Cells Non-Homologous Use: different than natural function Exclusivity: 12 Years from Approval (analogous provision in EU, JP) Other Barriers to Entry High Cost Requires Third Party Reimbursement (& FDA Approval) Hospital IRB oversight, liability for unapproved procedures Business Model Sell kit containing entire workflow to trauma center Cells processed at hospital-affiliated lab or point of care Multiple devices in development (Cesca MarrowXpress ) CEVA101: Barriers to Entry

17 Kit for Entire Work Flow Sold to Trauma Centers Materials for harvest / collection, shipping (if lab processed), infusion Interface with point of care cell separation device (Cesca, BioCardia) Could further include bone marrow harvest device (MarrowMiner) CEVA101: Commercial Kit

18 CEVA-D & CEVA102: Next Generation CEVA-D (Mechano-Transduction Device) Shear Stress Up-Regulates Anti-Inflammatory Gene Programs Ability to use fewer, more potent cells for any allo- or auto- cell therapy Substantially reduces COGS for all cell therapies Proof of Concept Completed In Vitro, In Vivo Tested with Adipose, Amniotic Fluid, Bone Marrow Mechano-Transduced Cells More Effective at Lower Dose than CEVA101 CEVA102 (Next Gen Cell Therapy) Autologous or Allogeneic Mechano-Transduced Cells Upregulated Anti-Inflammatory Gene Programs More Substantially Lower Dose Initial CEVA Indication: severe TBI in adults, children Partnering Strategy for Other Indications

19 Wall Shear Stress (WSS) Stimulates Anti-Inflammatory Mediators Promotes Signaling To Suppress TNF-α Improves Therapeutic Efficacy of MSCs in Rat Model of TBI CEVA-D & CEVA102: Key Publication

20 % TNF-α Production % TNF-α Production CEVA102: More Lower Dose A Suppression of TNF- α B Dosing for Equivalence of TNF- α Suppression

21 3x increase in PGE 2 production from cells treated for 3 hours in CEVA-D bioreactor PGE 2 : established marker for efficacy of MSCs CEVA-D: Increases PGE 2 Production

22 PGE2 (pg/ml) Percent CD86+ microglia CEVA-D: PGE 2 Suppresses M1 Genetically engineered MSCs expressing PGE 2 better suppress microglial M1 polarization in rat Overexpression of COX2 enzyme by transient transfection produces MSCs that secrete more PGE 2 and better suppress M1 microglial polarization PGE2 Production ** M1-type microglia p=0.05 Sham 600 haf19 haf19 EGFP 5 4 CCI haf haf19 COX2 3 haf19 EGFP haf19 COX2 0 PGE2 (pg/ml) 0 Ipsilateral Contralateral Kota et al. (2017) Stem Cells 35:

23 CEVA101: RMAT Designation (Granted) Regenerative Medicine Advanced Therapy (RMAT) Designation Granted for CEVA101 in November st Century Cures Act, effective 12/2016 Equivalent of Breakthrough designation for cell therapy Requirements Serious or life-threatening condition Preliminary clinical evidence of safety, efficacy Benefits Discussion with FDA at specific development meetings (increased access) Eligibility for Priority Review (BLA review reduced from 10 months to 6 months) Eligibility for Accelerated Approval (surrogate endpoints, post-approval studies) Eligibility for Fast-Track Approval ( rolling review of BLA parts)

24 CEVA101: Only 10 RMATs Granted as of 01/2018 As of 01/2018 (one year after availability), only 10 RMAT designations granted o Most Companies: presented Phase 2 data in request o Cellvation: Phase 1 in children, Phase 1/2 data in adults (total of 25 treated) Humacyte (Vascular Access, Hemodialysis) jcyte (Retinitis Pigmentosa) Athersys (MultiStem) Enzyvant (DiGeorge syndrome) Asterias (AST-OPC1, spinal cord injury) Juno (JCAR017; CAR-T) BlueBird Bio (Lentiglobin in SCID) Kiadis Pharma (ATIR101, blood disorders) Cellvation (CEVA101, traumatic brain injury) Mesoblast (Heart Failure, mesenchymal precursor cell)

25 CEVA101: End of Phase 1 Meeting (Completed) End of Phase 1 Meeting for CEVA101 (adults, children) Previous request postponed to first secure RMAT (granted 11/2017) RMAT notice requests Sponsor schedule Type B Meeting Purpose, Strategy Confirm design, endpoints of ongoing Phase 2 studies (adults, children) Secure FDA support for new imaging-based endpoints o CT Scans at 6-months demonstrate volumetric preservation o Known ~10% loss of brain volume 6 months post-tbi o Preservation improves long-term neurocognitive outcome Previous Studies: Glasgow Outcome Scale (GOS) Classic signal vs. noise conundrum Heterogeneity of TBI, limited classification categories Inability to distinguish clinical trajectories with sufficient fidelity

26 CEVA101: Early Market Access in Japan (Planned) Revised Pharmaceutical Affairs Law (JP), renamed PMD Act New pathway (2015), up to seven years approval with data monitoring Requirements: early trials demonstrate probable benefit, safety Cost: $200,000 to file IND equivalent, conduct meeting with MHLW Requires data in Japanese (likely 10-15), open JP site for adult study Timing: after EOP1 in US, 4Q2018

27 CEVA101: Market & Potential Sales Indication US Incidence EU Incidence $20K / Patient (50% penetration) Severe TBI in Adults ~200,000 ~50,000 ~$2B+ Severe TBI in Children ~50,000 ~15,000 ~$1B+ Potential for Early Market Access in Japan Revised Pharmaceutical Affairs Law May only Require Data in ~10 JP Patients

28 Near-Term Corporate Objectives Supplement Funding of Ongoing Phase 2 Studies Add Clinical Sites: accelerate outcomes, enhance data Pursue Early Access for CEVA101 in Japan under Revised Pharma Affairs Law Continue Development of Novel Bio-Reactor (CEVA-D) Engage Manufacturers Re Point of Care Cell Separation Further reduce COGs for CEVA101 Secure Additional Sources of Funding Evaluate Complimentary Cell Therapy Programs

29 Investment Considerations Novel Biologics, $Billion Markets (Orphan for Peds) Antiquated Standard of Care (No Approved Reparative Therapy) CEVA101: most advanced reparative therapy for severe TBI Three Previous Studies in 60+ Patients: Safe, Well-Tolerated, Effective Fully Funded Phase 2 Studies ($12M+ from NIH, DOD for ongoing studies) Most Recently Published in Stem Cells (11/2016) Equivalent of Breakthrough designation granted (RMAT, 11/2018) Phase 2 Data: in Peds as early as 1H2019, in Adults as early as 2H2019 CEVA-D & CEVA102: Preclinical data showing more lower cost $12M+ in NIH, DOD Funding Reduces Capital Requirement For More Information, Contact: Frank Taffy, Co-Founder, President, CEO, Board Member frank@helocyte.com