A Majority-Owned Subsidiary of Fortress Biotech JUNE 2017

Transcription

1 A Majority-Owned Subsidiary of Fortress Biotech JUNE 2017

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 Therapies for the Treatment of Severe Traumatic Brain Injury Programs from University of Texas Health Science Center (Houston) Two Technology Platforms, Most Clinically Advanced for Severe TBI Current Gen (CEVA101): autologous mononuclear cells for severe TBI Adult TBI: Phase 1 in patients published, Stem Cells, 11/2016 Pediatric TBI: Phase 1 in patients published, Pediatric Critical Care, 03/2016 Phase 2 Studies: ongoing, randomized, placebo-controlled in severe TBI o Data by 2H2018 in Pediatrics, by 1H2019 in Adults 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) $10M+ in NIH/DOD Grant Funding

4 Development Pipeline Preclinical Phase 1 Phase 2 Phase 3 CEVA101 MNCs for Pediatric TBI CEVA101 MNCs for Adult TBI CEVA102 Next-Gen for Pediatric TBI CEVA102 Next-Gen for Adult TBI CEVA-D Bioreactor (Device)

5 Fortress & Cellvation Leadership Fortress Biotech Management Lindsay A. Rosenwald, M.D. Executive Chairman Michael S. Weiss, J.D. Executive Vice Chairman Cellvation Management 20+ years experience Life Sciences Entrepreneur and Investor 20+ years experience Life Sciences Entrepreneur and Investor Cellvation Board of Directors Lindsay A. Rosenwald, M.D. Executive Chairman Michael S. Weiss, J.D. Director Frank Taffy, J.D. Director 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 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 Univesity of Texas Health Science Center Houston: Head of Neuro-Trauma Univesity of Texas Health Science Center Houston: Acute Care Surgery TBA 5

6 UT Health Scientific Team Charles S. Cox, Jr. M.D. Brijesh Gill, M.D. Pamela Wenzel, Ph.D. Scott Olson, Ph.D. Kevin Aroom, M.S. Program Leader, Surgeon-Scientist Surgeon, Engineer-Scientist, Entrepreneur Stem Biologist, Mechanotransduction MSC Biologist Biomedical Engineer Supinder Bedi, Ph.D Fabio Triolo, Ph.D. Neuroscientist cgmp Cell Manufacturing Sponsored Research Agreement Between UT-Health and Cellvation

7 Fortress Biotech: Snap-Shot Biopharmaceutical company acquiring, developing and commercializing novel pharmaceutical and biotechnology products Provides funding and management services to its subsidiaries ( Fortress Companies ), including Cellvation Listed on NASDAQ: FBIO Market Cap as of 3/13/17 ~$175M 7

8 Fortress Companies & Shared Services Checkpoint Therapeutics Mustang Bio Avenue Therapeutics Executive Chairman / Board Business Development Manufacturing Legal Journey Medical Corporation Clinical Trials Accounting Escala Therapeutics Helocyte Cellvation 8

9 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 Adults: ~200K annually Peds: ~50K annually (ORPHAN) Standard of Care No Approved Reparative Therapy Focused on Control of Inter-Cranial Pressure Last Resort: Decompressive Craniectomy Volumetric & Structural Loss Following TBI 8-12% of white matter, gray matter, other regions 9

10 CEVA101: Pre-Clinical Data (Rodent TBI model) BBB Permeability Preserved Reduced Neuroinflammation BMMNC associated with apoptosis of activated microglia within hippocampus. Green- Microglia Red-Cleaved Caspase-3 Merged images-apoptotic microglia Microglial morphology: Amoeboid=M1 Ramified=quiesecent (M0) Bedi, SS. J Trauma 2013 CONFIDENTIAL

11 Treatment Effect in the Acute Setting? Immunomodulation NOT Engraftment Preclinical Rodent Findings Cell therapy improves blood brain barrier integrity Clinical Question Reduced treatment intensity (PILOT scores) in Children? Cell Therapy Cell Therapy Cells travel to spleen CCI = Controlled Cortical Injury Without Cell Therapy

12 CEVA101: Clinical Overview Autologous Bone-Marrow Derived Mononuclear Cells Mechanism: dampening of immune response to injury (to reduce secondary injury) Clinical Benefit: reduced therapeutic intensity, structural preservation CEVA101 (Pediatric Severe TBI) Phase 1 (completed): 10 patients, single-dose, severity-matched control o Safe, well-tolerated, reduced therapeutic intensity, volumetric preservation o Re-Published w New Controls: Liao, Pediatric Critical Care (2016) Phase 2 (31 of 50 enrolled): multi-center, blinded, randomized, placebo-control o Fully-funded by NIH (~$4M), additional sites to accelerate o Readout By 2H2018, Approval by 2021? (Pediatric Voucher Potential) CEVA101 (Adult Severe TBI) Phase 1 (completed): 25 patients, dose-escalation, time-matched control o Safe, well-tolerated, structural preservation (builds on pediatric study) o Biomarkers: reduction in pro-inflammatory cytokines (IL1, IFNγ, TNFα) o Published: Cox, Stem Cells (2016) Phase 2 (6 of 55 enrolled), single-site, blinded, randomized, placebo-control o Fully-funded by DOD (~$7M), additional sites to accelerate o Readout by 1H2019, Approval by 2022? 12

13 CEVA101 Phase 1: Reduced Therapeutic Intensity in Pediatric TBI PILOT Score CP (mmhg) ICP (mmhg) Daily Pediatric Intensity Level of Therapy (PILOT) 15 Average Maximum Daily ICP Values p< p< Average Maximum Daily ICP Values p< Cell Infusion Admission Day p=0.001 p<0.01 p=0.03 Week 1 Weeks 2-3 Time Matched Controls Aggregate Controls Phase I Treated

14 Previous Studies Show: Volumetric Loss After Pediatric TBI p=0.065 P=0.003 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 CONFIDENTIAL

15 CEVA101 Phase 1: Volumetric Preservation in Pediatric TBI Post-TBI MRI at Month 1 (Scan 1) versus Month 6 (Scan 2) Preservation of Grey Matter (GM), White Matter (WM), Intracranial Volume (ICV) CONFIDENTIAL 16

16 CEVA101 Phase 1 : Adult TBI Published in Stem Cells Phase 1 Dose-Escalation in 25 Patients 5 controls, 5 patients in 3 dose cohorts, 5 more controls Bone marrow harvest, reinfusion within 48 hours of injury Key Findings No Serious AEs relating to harvest, infusion Down-Regulation of Key Inflammatory Cytokines (IL1B, IFNγ, TNFα) Preservation of Critical Regions, Correlates with Functional Outcomes 16

17 % Difference in WM Volume CEVA101 Phase 1: Volumetric Preservation (WM) in Adult TBI 0.0% % change in cortical WM volume -0.5% -1.0% -1.5% -2.0% -2.5% -3.0% -3.5% -4.0% Tx- Tx+ %Cor WM Vol [mm3] -3.6% -0.6% CONFIDENTIAL

18 CEVA101 Phase 1: Structural Preservation in Adult TBI FA CC Tracks at tp1 and tp2 Corpus Callosal Fiber Tract Fractional Anisotropy: Structural Preservation via Cellular Therapy CC Tractography: Control (TX-) CC Tractography: Treated (Tx+) FA F Early Scan-1 month Late Scan-6 months Tx- Tx+ FA tp FA tp DTI can be used as an imaging endpoint to quantify structural preservation in TBI clinical trials. Moderate to large treatment effect size was demonstrated at the corpus callosum pointing to the feasibility of a Phase 2b trial using BMMNC in TBI.

19 Why Autologous versus Allogeneic? Autologous Cells: minimally manipulated but protected as 351 Biologic in US Based on Non-Homologous Use : different 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) All 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): ~$30K per dose Equal or Better Safety and Efficacy Based on data in 60+ patients (adult stroke & TBI, pediatric TBI) Compared to Athersys allogeneic data in stroke

20 Commercial Kit Sold to Trauma Centers Kit for Entire Work Flow Sold to Trauma Centers Contains Bone Marrow Harvest Device (MarrowMiner) Interface with Point of Care cell separation device (Cesca, BioCardia) Materials for collection, shipping (if lab processed), infusion

21 Barriers to Entry (CEVA101) Protected as 351 Biologic Minimally-Manipulated Autologous Cells Non-Homologous Use: different than natural function Exclusivity: 12 Years from Approval (analogous provision in Japan) Potential for Regenerative Advanced Therapy Designation in US CEVA101 for Peds: Orphan, Accelerated Approval Voucher 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 harvest / re-infusion workflow Cells processed at hospital-affiliated lab or Point of Care o Multiple devices in development (Cesca MarrowXpress )

22 CEVA-D / CEVA102 Next Generation CEVA-D (Mechano-Transduction Device) Shear Stress Induces Anti-Inflammatory Gene Programs o o Requires fewer cells for any allo- or auto- cell therapy Substantially reduces COGS for all cell therapies Proof of Concept Completed In Vitro, In Vivo o o Tested with Adipose, Amniotic Fluid, Bone Marrow More Effective at Lower Dose than CEVA101 CEVA102 (Next Gen Cell Therapy) Autologous or Allogeneic Mechano-Transduced Cells Up-regulated anti-inflammatory genes o More Lower Dose Initial Indication: severe TBI in adults, children 22

23 CEVA-D / CEVA102 Wall Sheer Stress (WSS) Stimulates Anti-Inflammatory Mediators Promotes Signaling To Suppress TNF-α Improves Therapeutic Efficacy of MSCs in Rat Model of TBI CONFIDENTIAL

24 CEVA-D / CEVA102 Rationale: MSC-MT Suppress TNF release via PGE 2 mediated MOA TNF-α cytokine suppression assays highlight functional enhancement of MSC immunomodulation. Human MSCs preconditioned by mechanical force (15 dyne/cm2 shear stress for 3 hrs) are placed in static co-culture with lipopolysaccharide (LPS) or phytohaemagglutinin (PHA)-activated splenocytes consisting of macrophages, neutrophils, NK, B, and T cells. (A) TNF-α secretion by splenocytes is reduced by 10-50% when MSCs are transiently sheared. Lower values correspond to greater anti-inflammatory potency. (B) Inhibition of COX2 (Indomethacin, 10 μm; NS-398, 10 μm) and NF-kB (BAY , 10 μm) abrogate the positive effects of shear stress, whereas ectopic dmpge2 (10 μm) mimics MSC suppression. CONFIDENTIAL

25 CEVA102: More Lower Dose CONFIDENTIAL

26 Market, Potential Sales Indication US Incidence EU Incidence Severe TBI in Adults Severe TBI in Children $20K / Patient (50% penetration) ~200,000 ~50,000 ~$2B+ ~50,000 ~15,000 ~$1B+ Potential for Early Market Access in Japan Revised Pharmaceutical Affairs Law May only Require Data in ~10 JP Patients Access for CEVA101 by 1H2019 or sooner Potential Sales for 500 Patients: $10M+ 26

27 Near-Term Corporate Objectives Pursue Early Access in Japan under Revised Pharma Affairs Law Complete End of Phase 1 Meeting with FDA Substantive feedback on development, endpoints Supplement Funding of Ongoing Phase 2 Studies Add Clinical Sites: accelerate outcomes, enhance data Fund Development of Novel Bio-Reactor (SRA with UTH) Engage Manufacturers Re Point of Care Cell Separation (further reduce COGs) Secure Additional Sources of Funding, Esp Non-Dilutive Grants (SBIR, CIRM) Complete Debt / Equity Financing

28 Capital Requirement Thru 1H2019: ~$10M* *supplementing ~$10M in NIH/DOD funding Pediatric TBI $2M, 20% Device, Next-Gen Cells $2M, 20% Read-Outs By End of 2018: Phase 2 in Pediatric TBI Phase 2 in Adult TBI Competion of Production- Stage Bioreactor Adult TBI $2M, 20% G&A $2M, 20% New Programs $2M, 20% Supplementing NIH, DOD Funding To Accelerate Outcomes, Enhance Quality of Data Adult TBI Pediatric TBI Device, New Cells G&A New Programs 28

29 Investment Considerations Novel Biologics, $Billion Markets (Orphan for Peds) Antiquated Standard of Care (No Approved Therapy) CEVA101: most advanced reparative therapy for severe TBI Three Previous Studies in 60+ Patients: Safe, Well-Tolerated, Effective Fully Funded Phase 2 Studies ($10M from NIH, DOD) Most Recently Published in Stem Cells (11/2016) Phase 2 Data: in Peds by 1H2018, in Adults by 1H2019 CEVA-D & CEVA102: preclinical data showing more lower cost $10M in NIH, DOD Funding Reduces Capital Requirement For More Information, Contact: Frank Taffy, Co-Founder, President, CEO, Board Member frank@helocyte.com 29