Abeona Therapeutics Inc. · NASDAQ:ABEO
Abeona Therapeutics — Plasmatech Biopharmaceuticals — Investor Presentation (May 2015)
41 slides from Abeona Therapeutics's investor presentation, May 7, 2015
Slide 1: Investor Presentation
NASDAQ: PTBI Investor Presentation
Slide 2: Safe Harbor Statement
This presentation contains certain statements that may be forward - looking within the meaning of Section 27 a of the Securities Act of 1933 , as amended, including statements relating to the product portfolio and pipeline and clinical programs of the company, the market opportunities for the Plasma
Slide 3: Strategic Imperative: Progression of Cell Therapy to Gene Therapy
2 1 st Generation 2 nd Generation 3 rd Generation Plasma fractionation (ethanol based) • Albumin • Platelets • IVIG New Cell Therapy Technologies 1950 - 1980s New SDF ™ plasma process enables and validates orphan proteins and targets requiring periodic treatments : • A1PI – SDF Alpha • IVIG – SDF Ga
Slide 4: PlasmaTech & Abeona Merger Overview
3 PlasmaTech & Abeona Merger Building a world class cell & gene therapy company focused on rare diseases MPS IIIA & MPS IIIB Programs ( Abeona ) • AAV - based gene therapies for MPS III & MPS IIIB • Orphan Drug and Pediatric Rare Disease Designations from FDA • Plan to file IND in MPS IIIB in June 2
Slide 5: Abeona Therapeutics Overview
4 Abeona Therapeutics Overview Abeona – Roman goddess, protector of children leaving home x Founded in March 2013 x Lead products are licensed gene therapy technology from Nationwide Children’s Hospital (Columbus, OH) x Lead products : AAV9 gene therapy for MPS IIIA & MPS IIIB x Received the FDA Orp
Slide 6: Sanfilippo Syndromes MPS III
5 Sanfilippo Syndromes MPS III x Rare lysosomal storage disease affecting children x Deficiency in one of four cellular enzymes ( MPS IIIA, IIIB, IIIC and IIID ) x Onset between ages 2 and 6; inability to walk by 10. Progressive, severe neurological and muscular disorder x Aggressive behavior, seizu
Slide 7: Scientific Team
6 Scientific Team Nationwide Children’s Scientific Advisors Kevin Flanigan , MD Clinical Investigator Doug McCarty, Ph.D. Scientific Founder Haiyan Fu, Ph.D. Scientific Founder Joseph Muenzer , Ph.D. Univ of North Carolina Maria Escolar, MD University of Pittsburgh Center for Neurodegenerative Disor
Slide 8: Global Foundation Support
7 Global Foundation Support 2013 Global Genes “Champions of Hope” Award – Co - Recipients USA Canada USA Switzerland USA Spain Mexico Australia USA USA Spain USA
Slide 9: Abeona's Gene Therapy Approach MPS III
8 Abeona’s Gene Therapy Approach MPS III x AAV9 single injection gene therapies, intravenous delivery for MPS IIIA and MPS IIIB x Lysosomal Storage Diseases • Ideal candidates for gene therapy – Bystander cell uptake • Requires lower levels of delivery to cells for therapeutic benefit • Fast track t
Slide 10: Normalization of Behavior and Muscle Function in MPS IIIB Mice
9 Normalization of Behavior and Muscle Function in 4 - 6 Week Old MPS IIIB Mice after a Single Injection of rAAV9 - CMV - hNAGLU 5.0 - 5.5 months old (4 months post - injection) * # # # * * * * * ^ ^ & * & & 0 10 20 30 40 50 60 70 1 2 3 4 Latency to find platform (sec) Days of testing a. Hidden task
Slide 11: IV Infusion of rAAV9-hNAGLU Normalized Survival in MPS IIIB Mice
10 IV Infusion of rAAV9 - hNAGLU Vector at 4 – 6 Weeks of Age Normalized The Survival in MPS IIIB Mice 0 20 40 60 80 100 120 1 4 7 10 13 16 19 22 25 28 31 Survival (%) Age (months) Survival (rAAV9 - CMV - hNAGLU) +/+ -/- AAV9-L AAV9-H Survival Increased 100% after single IV treatment
Slide 12: Critical Abeona Competitive Advantages MPS III
11 Critical Abeona Competitive Advantages MPS III x Pre - clinical Effectiveness : Only MPS therapy to demonstrate in cognitive , muscular and survival benefits! x Neurotropism : Only therapy in development that cross blood brain barrier (AAV9) • Single IV injection, compared to multiple injections
Slide 13: Cell & Gene Therapy Companies Comparables
12 Cell & Gene Therapy Companies Comparables Company (Ticker) Market Cap Indication – Stage of Development Avalanche Bio (AAVL) $820.1 M AAVs for opthalmology – plan to file IND 2H 2015 Bluebird Bio (BLUE) $4.56 B Multiple programs ( lenti , CAR T) – multiple clinical stage programs Bellicum Pharma
Slide 14: Alpha-1 Deficiency – Inherited COPD
13 Alpha - 1 Deficiency – Inherited COPD Alpha - 1 x AATD is an under - diagnosed hereditary condition • Genetic condition whereby insufficient AAT protein produced by liver; leads to COPD and liver disease • Roughly 1 in every 2,500 Americans have AATD; 5 times more prevalent than Cystic Fibrosis •
Slide 15: SDF Process: Benefits over Cohn
SDF Process 14 Kinder, Gentler x Simple 2 - Stage Sodium Citrate Precipitation + Diafiltration x No ethanol or PH changes like Cohn method x Less denaturing of select proteins x Roughly 2 - 3 day process, versus 6 - day for Cohn Yield Improvements x Alpha - 1 yield increase ~10X x IVIG yield increas
Slide 16: Alpha-1 Opportunity
Alpha - 1 15 Alpha - 1 Opportunity x Orphan Drug Characteristics • Up to 300,000 potential patients in US and Europe; only roughly 10,000 on replacement therapy today • A1PI replacement therapy is reimbursed at $100,000 per patient annually • Patients on therapy for 22 years (average) x High value,
Slide 17: SDF Gamma: Intravenous Immunoglobulin (IVIG)
SDF Gamma 16 Neurology Hematology Dermatology Other x Guillain Barre x Immune thrombo - cytopenia x Kawasaki Syndrome x Primary antibody deficiencies x Lambert Eaton Syndrome x Post BMT x Dermatomyositis x Vasculitis x Multifocal motor neuropathy x Myeloma and CLL x Toxic epidermal necrolysis x Auto
Slide 18: Leaders in Alpha-1 and Mucositis
Leaders in Alpha - 1 and Mucositis 17 Eugene Zurlo, BS, MS Pharmacy, Chairman ▪ 56 years experience ▪ Founder/Chairman/ Inventor Plasma Technologies, LLC (Licensor) ▪ Baxter Hyland, Millipore, NY Blood Center, Alpine Biologics, Ayerst Laboratories Charlie Strange, MD ▪ Professor Pulmonary, Critical
Slide 19: Hydrogel Polymer Products
Hydrogel Polymer Products 18 Two FDA - cleared Commercial Products x Patented mucoadhesive hydrogel delivery system enables extended delivery of drugs to mucosal tissue x MuGard® for Oral Mucositis (“OM”) • $ 1 billion market, underserved, few competing products with demonstrated clinical benefit •
Slide 20: Management & Board of Directors
Board of Directors Management Management & Board of Directors 19 Tim Miller, Ph.D. – President & CEO ▪ Extensive scientific, product development and clinical operations experience ▪ Multiple IND submissions ▪ Ph.D. in Pharmacology (Gene Therapy/Cystic Fibrosis), Case Western University Harrison Wehn
Slide 21: Capitalization Table
Recent events: • Does not include 3,979,761 common shares to be issued to Abeona upon closing • Does not include 577,756 “old” warrants outstanding with WAEP of $46.50 • No long term debt, no convertible preferred stock Capitalization Table 20 Capitalization Shares Outstanding WAEP Outstanding commo
Slide 22: Milestones
Milestones 21 Milestones Timing Finalize Abeona acquisition May 2015 File IND for MPS IIIB June/July 2015 First Patient In, MPS IIIB in USA Sept./Oct 2015 Complete and file IND for MPS IIIA 2H 2015 First Patient in, MPS IIIB in Europe, Australia 1H 2016 In - license Complementary Gene Therapy Progra
Slide 23: Investment Highlights
Investment Highlights 22 PlasmaTech & Abeona Merger Building a world class cell therapy company focused on rare diseases MPS IIIA & MPS IIIB Programs ( Abeona ) • AAV9 gene therapies for MPS III & MPS IIIB • Orphan Drug and Pediatric Rare Disease Designations from FDA • Plan to file IND in MPS IIIB
Slide 24: gy plasmarech’
gy plasmarech’ IOPHARMACEUTICALS
Slide 25: Addendum: Abeona Pre-Clinical Data
24 Addendum 1 Abeona Pre - Clinical Data
Slide 26: Clearance of Lysosomal Storage Pathology in Liver of MPS IIIB Mice
25 Clearance of Lysosomal Storage Pathology in the Liver of MPS IIIB Mice after an IV rAAV9.NAGLU Infusion 6 months post - injection . The red arrows indicate the nuclei of liver cells . Note the decrease in “storage lesions” or holes in the cells from the liver of a treated animal on the left . Thi
Slide 27: IV Delivery of rAAV9.CMV.NAGLU Induces Clearance of GAG Storage
1.5E13 vg/kg 26 IV Delivery of rAAV9.CMV.NAGLU Induces Clearance of Lysosomal GAG Storage in the CNS and Somatic Tissues 6 months post - injection Lower bars are better. Demonstrates that treated IIIB mice have reduced GAG content, similar to unaffected animals, in multiple tissues compared to untre
Slide 28: AAV9-CMV-NAGLU Corrects Secondary Neuropathology in MPS IIIB Mice
27 IV Delivered AAV9 - CMV - NAGLU Corrects Secondary Neuropathology in MPS IIIB Mice: Astrocytosis and Neurodegeneration Cerebral cortex Thalamus Striatum No treatment ( 7 month) AAV 9 treated (End) * * * * 0 20 40 60 80 100 No. astrocytes CTX ST TH BS a. MPS IIIB MPS IIIB +AAV9 * 0 5 10 15 No. cel
Slide 29: scAAV9 Delivered by IV Demonstrates Systemic Transduction in Mice
28 scAAV9 Delivered by IV Demonstrates Systemic Transduction in Mice Self - complementary AAV9 virus delivered intravenously to mice. The AAV9 is delivering a gene to make the mouse glow where the AAV9 got into cells, referred to as “expression”. This demonstrates that by 7 days post - injection, th
Slide 30: IV Delivery of rAAV9.CMV.NAGLU Induces Clearance of GAG Storage
29 IV Delivery of rAAV9.CMV.NAGLU Induces Clearance of Lysosomal GAG Storage in the CNS and Somatic Tissues rAAV9 - mediated rNAGLU expression in MPS IIIB mouse brain Vector dose (vg/kg) AOI NAGLU activity (% of wt levels) 1mo pi 3mo pi 6mo pi 12mo pi End 1x10 13 4 - 6wk 60 - 560% 80 - 440% 60 - 312
Slide 31: MPS IIIB Toxicology Study in Non-Human Primates
30 MPS IIIB – 6 Month Toxicology Study in Non - Human Primates IV delivery of rAAV9-CMV-hNAGLU in NHP NHP Age (y) *AAV9 Abs (titer) **IS Vector dose (vg/kg) Termination (pi) Group 1 NT1 10.3 1:64 - Saline 6wk S1 10.5 1:32 - 1E13 6wk S2 11.0 Neg - 1E13 3mo Group 2 NT-2 2.3 Neg - Saline 3mo M1 2.3 Neg
Slide 32: Persistence of NAGLU Expression in CNS in Non-Human Primate
31 Persistence of NAGLU Expression in CNS at 6 Month in Non - Human Primate (2 yr old; 2 x 10 13 vg/kg) Brain and somatic NAGLU activity remains supraphysiologic at 6 months despite modest decreases in peripheral serum NAGLU levels Untreated, wild type animal
Slide 33: No Evidence for Autoimmune Responses in Non-Human Primates
32 No Evidence for Autoimmune Responses in Non - Human Primates x Antibody responses to human NAGLU was observed in NHP However : • No evidence for autoimmune pathology in any tissues at 6 months post - injection • MPSIIIB mice – null for NAGLU – did not show evidence for clearance of transduced cel
Slide 34: Systemic scAAV9 Broadly Distributed in CNS of Non-Human Primates
33 Systemic Delivery of scAAV9 is Broadly Distributed in the CNS of Non - Human Primates A dose of scAAV9 - CBA - GFP was injected into 3 year old cynomolgous macaque via saphenous vein. GFP expression in the brain was assayed at 3 weeks post injection by immunohistochemistry in 40 um coronal sectio
Slide 35: scAAV9-U1a-SGSH Increases SGSH Activity in MPS IIIA Mice
34 Intravenous Delivery of scAAV9 - U1a - SGSH Increases SGSH Activity In MPS IIIA Treated Mice 8 Months Post - Treatment MPS IIIA mice were treated at the indicated ages ( ie - “ 3 mo ” indicates a 3 month old IIIA mouse treated with an IV dose of scAAV - U 1 a - SGSH) and the indicated tissues wer
Slide 36: IV scAAV9-U1a-SGSH Reduces GAG Content in CNS and Peripheral Organs
35 IV scAAV9 - U1s - SGSH Reduces GAG Content in CNS and Peripheral Organs > 9 months 0 0.5 1 1.5 2 2.5 3 3.5 4 Brain Hrt Lung Mus GAG contents ( μ g/mg tissue) Tissue GAG (endpoint) WT NT 1mo 2mo 3mo 6mo 0 1 2 3 4 5 6 7 8 LIV Kid Spl Int GAG contents ( μ g/mg tissue) Tissue GAG (endoint) WT NT 1mo
Slide 37: scAAV9-U1a-SGSH Corrects Behavioral Deficiency in MPS IIIA Mice
36 IV Delivery of scAAV9 - U1a - SGSH Corrects Behavioral Deficiency in MPS IIIA Mice with Beneficial Effects lasting 1 Year Post - Treatment ^ ^ * * ^ # @ @ # ^ * ^ 15 25 35 45 55 65 1 2 3 4 Latency (sec.) Days of testing Task Acquisition (hidden ) wt IIIA 1mo 2mo 3mo 6mo # # # @ * * * * 15 25 35 4
Slide 38: scAAV9-UA1-SGSH Increases Survival of MPS IIIA Mice
37 IV Delivery of scAAV9 - UA1 - SGSH Increases Survival of MPS IIIA Mice Groups of MPS IIIA mice were treated at 1 mo age with different doses (A), or at different ages with vector (B) of scAAV9 - U1a - SGSH vector by IV injection. Life spans were compared to wt or untreated MPS IIIA mice. A B
Slide 39: Preclinical Data Summary – IV Delivery of AAV9 Vectors
38 Preclinical Data Summary – IV Delivery of AAV9 Vectors For Treatment of MPS IIIA and MPS IIIB • MPS III mice were treated at ages 1mo, 2mo, 3mo, 6mo and 9mo were treated with an intravenous injection of AAV9 vector carrying correct version of gene. • The treatment led to the restoration of MPS II
Slide 40: MPS IIIA and MPS IIIB Natural History Study
39 MPS IIIA and MPS IIIB Natural History Study • Study Site – Nationwide Children’s Hospital, Ohio, USA • Enrollment complete: 25 subjects, 15 MPS IIIA and 10 MPS IIIB • FDA requested Natural History study to support clinical endpoints • Study visits – assessments at Months 0, 6, and 12: x Neurocogn
Slide 41: Contacts
Contacts Jeff Davis Chief Operating Officer Phone : 212.786.6201 Email : jdavis@plasmatechbio.com Andre’a Lucca Director of Communications Phone : 212.786.6208 Email : alucca@plasmatechbio.com 40
Plasmatech Biopharmaceuticals — Investor Presentation (May 2015) on 6ix