NASDAQ: ABEO

Transcription

1 NASDAQ: ABEO 1

2 Safe Harbor Statement This presentation contains certain statements that may be forward-looking within the meaning of Section 27a 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 all of the company s products and product candidates, and the company s goals and objectives. These statements are subject to numerous risks and uncertainties, including but not limited to the risks detailed in the Company s Annual Report on Form 1-K for the year ended December 31, 216, and other reports filed by the company with the Securities and Exchange Commission. This presentation does not constitute an offer or invitation for the sale or purchase of securities or to engage in any other transaction with Abeona Therapeutics or its affiliates. The information in this presentation is not targeted at the residents of any particular country or jurisdiction and is not intended for distribution to, or use by, any person in any jurisdiction or country where such distribution or use would be contrary to local laws or regulations. The Company undertakes no obligations to make any revisions to the forward-looking statements contained in this presentation or to update them to reflect events or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise. 2

3 Rare Disease Pipeline 3

4 Global Leader in Developing Novel Rare Disease Therapies Sanfilippo syndromes Epidermolysis bullosa Batten Disease CMC AIM TM Vector Platform ABO-12 ABO-11 EB-11 EB-21 ABO-21 ABO-22 E. Linton Center for Rare Disease Pipeline 4

5 Global Approach to Development Nationwide Children s Hospital ABO-12, ABO-11 Global Clinical Trials MPS IIIA: US, EU & Australia MPS IIIB: US & EU RDEB: US Battens: US & EU (218) Supportive Natural History Studies Stanford University EB-11 University of Rochester ABO-22, ABO-22 Clinico de Santiago ABO-12, ABO-11 Hamburg-Eppendorf ABO-21, ABO-22 Adelaide Women s & Children s Hospital ABO-12 5

6 Sanfillipo Syndrome ABO-12 Data Update World leading clinical program for MPS IIIA ABO-11 World leading clinical program for MPS IIIB Orphan Drug Designation (FDA) Orphan Drug Designation (EU) Rare Pediatric Disease Designation (FDA) Fast Track Designation (FDA)* * ABO-12 6

7 Sanfilippo Syndrome (MPS III) Sanfilippo syndromes (MPS IIIA & IIIB) are inherited monogenic disorders that cause lysosomal enzyme deficiency Two most common forms, each categorized by a deficient enzyme: - MPS IIIA (SGSH) - MPS IIIB (NAGLU) Abnormal accumulation of glycosaminoglycans (GAGs) (heparan sulfate) Aggressive behavior, seizures, loss of speech/vision, inability to sleep 7% of children with MPS III do not reach age 18 Normal cell No approved treatments available Incidence is estimated to be 1 in 7, births Two ongoing global clinical trials ABO-12 (scaav-sgsh) for MPS IIIA USA, EU, Australia clinical sites ABO-11 (AAV-NAGLU) for MPS IIIB screening initiated USA and EU clinical sites Supportive Natural History Study in 25 subjects: 15 MPS IIIA & 1 MPS IIIB 7 Cell with lysosome deficiency

8 Phase 1/2 Trial Pivotal Expansion for MPS IIIA Phase 1/2 ABO-12 (scaav-sgsh) open-label, doseescalation clinical trials - Cohort 1: 5 X 1 12 vg/kg (n=3 subjects) - Cohort 2: 1 X 1 13 vg/kg (n=3 subjects) - Cohort 3: 3 x 1 13 vg/kg (2 patients treated) - Expect to enroll total of 6-9 additional patients at three global sites: US, Spain and Australia Primary objective is safety, with secondary efficacy endpoints: - Reduction in heparan sulfate (HS) and/or Total GAG - Reduction in liver volume by MRI as a measure of disease modification - Leiter International Performance Assessment after 6 and/or 12 months post treatment - Vineland Adaptive Behavior Assessment System and Child Behavioral Checklist - Brain MRI volumetric changes 8

9 Well-tolerated through >2 days follow up M P S - I I I A - 2 M P S - I I I A - 3 M P S - I I I A Cohort 2 Cohort 1 U / L U / L S c r e e n i n g S c r e e n i n g D a y - 1 D a y - 1 D a y 1 D a y 1 D a y 1 D a y 7 D a y 1 4 D a y 3 D a y 4 5 D a y 6 D a y 7 5 D a y M P S - I I I A - 5 D a y 7 D a y 1 4 D a y 3 D a y 4 5 D a y 9 D a y 6 D a y 9 O f f s t e r o i d D a y 7 5 M o n t h 6 D a y 9 M o n t h U / L U / L S c r e e n i n g D a y - 1 S c r e e n i n g D a y 1 D a y - 1 D a y 7 D a y 1 D a y 1 4 D a y 7 D a y 3 D a y 4 5 D a y 6 D a y 7 5 D a y M P S - I I I A - 6 D a y 1 4 D a y 3 D a y 4 5 D a y 6 D a y 9 D a y 7 5 O f f s t e r o i d D a y 9 M o n t h 6 O f f s t e r o i d M o n t h 1 2 M o n t h U / L U / L S c r e e n i n g S c r e e n i n g D a y - 1 D a y - 1 D a y 1 D a y 1 D a y 7 D a y 1 4 D a y 3 D a y 4 5 D a y 6 D a y 7 5 D a y M P S - I I I A - 7 D a y 7 D a y 1 4 D a y 3 D a y 4 5 D a y D a y 6 D a y 9 O f f s t e r o i d D a y 7 5 M o n t h 6 D a y 9 M o n t h D a y ALT and AST values (U/L). Purple = ALT values of subject (solid line) and normal range (dashed lines). Green = AST values of subject (solid line) and normal range (dashed lines). 9 D a y

10 Absence of immune response Cohort 2 Cohort 1 1

11 ABO-12 Demonstrates Durable, Dose- and Time- Dependent Reduction in CSF HS Dose and time-dependent reduction of CSF heparan sulfate (HS) fragments indicate ABO-12 crosses the blood-brain barrier % Day 3 Day 18 Day 36 % Reduction in CSF Heparan sulfate (HS) -1% -2% -3% -4% -5% -25.8% -58.7% -48.8% -5.% -69.3% Cohort 1-6% -66.7% Cohort 2-7% Cohort 3 11

12 Dose Escalation Enhances Reduction in Urine HS % Day 3 Day 6 Day 9 Day 18 Day 36-1% -2% -29.2% -29.2% -3% -64.2% -64.2% -54.2% % REDUCTION IN URINE HEPARAN SULFATE (HS) -4% -5% -6% -7% -8% -9% -54.% * * -93.8% -65.2% *** * -63.1% *** ** * = P<.5 ** = P=.57 *** = P<.1-1% Cohort 1 Cohort 2 Cohort 3 12

13 ABO-12 significantly reduces Cohort 1 liver volumes at 1 year post-treatment (p<.5) % Screening Day 3 Day 18 Day 36 Absolute % Change -1% -2% -3% -4% -5% -6% -7% Cohort 1 (n=3) -8% Cohort 2 (n=2) -9% Cohort 3 (n=1) -1% -39% -57% -46% -76% -79% -8% % Normal Liver Volume Cohort 1 Subject A Subject B Subject C P value Screening 225% 22% 225% - Day 3 183% 174% 157%.13 Day % 15% 119%.3 Day % 149% 116%.4 % Normal Liver Volume Cohort 2 Subject D Subject E P value Screening 211% 194% - Day 3 171% 157%.73 Day % 14%.3 13 Cohort 3 % Normal Liver Volume Subject D Screening 234% Day 3 158%

14 ABO-12 Preserves deep brain architecture 1 year post-injection Basal ganglia Functions -Voluntary movements -learning -emotion Thalamus Damage: -Relay station -Sleep -Memory Putamen Damage: -Movement -Learning Pallidum Damage: -Muscle tremors - Motor skills 14

15 Deep Brain Architecture Stabilization: Thalamus Volume 1 Total Thatlamic Volmue Reudction (cmâ3) Baseline to 12 months Baseline 12 Months.42 Avg. 15% Improvement over Controls -.8 Cohort 1 (n=2) NHS Control (n=8) * P<.5 Goooijers et al., Neurorehabilitation and Neural Repair De Jong et al., Brain

16 Deep Brain Architecture Stabilization: Putamen Volume Total Putamen Volume Reduction (cmâ3) Baseline to 12 months Avg. 69% Improvement over Controls -3 Cohort 1 (n=2) Control (n=8) ** P<.5 Reduced volume loss in both the Thalamus and Putamen has been linked to both cognitive and motor performance deficits in both Alzheimer s disease 1 and Traumatic Brain Injury 2 16

17 Deep Brain Architecture Stabilization: Corpus Callosum Volume Total Corpus Callosum Volume Reduction (cmâ3) Baseline to 12 months Avg. 96% Improvement over Controls -.6 Cohort 1 (n=2) Control (n=8) 17

18 Brain Architecture Stabilization: Total Cortical Thickness Average Total Total Cortical Thickness Average Reduction (cmâ3) Baseline to 12 months Avg. 76% Improvement over Controls -.7 Cohort 1 (n=2) Control (n=8) 18

19 Neurological Clinical Benefit Neurocognitive assessment Leiter-3 Nonverbal IQ Scale 15 Slope Change over 12 months Baseline C1 (n=2) Month 12 One patient was unabled to be scored onto baseline and month 12 19

20 ABO-12 significantly improved 86.4% Vineland Adaptive Behavior Scale p=.5 at 1 year Vineland NHS showed a ~7 point decline over 6 months Cohort 1 Improved 86.43% over control 2 2

21 ABO-11 for Treatment of MPS IIIB Pre-clinical data - ABO-11 Single IV infusion of ABO-11 at 4-6 weeks of age normalized the survival in MPS IIIB mice - Single IV Delivery of ABO-11 induced clearance of lysosomal GAG storage in the CNS and somatic tissues - Demonstrates that treated IIIB animals have normalized GAG content, similar to unaffected animals, in multiple tissues compared to untreated IIIB animals (with exception of kidney) Phase 1/2 open-label, dose-escalation clinical trials - Two dose cohorts of n=12-15pts via intravenous injection - Cohort 1 (Low Dose): 2 X 1 13 vg/kg (n=3 subjects) - Cohort 2 (High Dose): 5 X 1 13 vg/kg (n=12-15 subjects) - Clinical sites: United State and Spain - Enrollment to commence shortly Source: Fu et al (211) Correction of Neurological Disease of Mucopolysaccharidosis IIIB in adult mice by raav9 Trans-Blood-Brain Barrier Gene Delivery, Mol. Ther

22 EB 11 Recessive Dystrophic Epidermolysis Bullosa Breakthrough Therapy for Severe EB Orphan Drug Designation (FDA) Orphan Drug Designation (EU) Rare Pediatric Disease Designation (FDA) Fast Track Designation (FDA) 22 Breakthrough Therapy Designation

23 EB-11 Autologous Gene Therapy EB-11: Ex-vivo Cell Therapy - gene therapy correction of patient cells to replace COL7A1 cdna EB-11: gene-corrected skin treatment EB-11 ready for application 23 23

24 Supportive Natural History Study 128 RDEB Subjects - Clinical Trial Readiness Multi-year Enrollment complete: - 1,436 wounds (1,41 recurrent wounds/395 chronic open wounds) 1% of patients reported a history of either chronic open wounds or recurrent wounds with no healing > 12 weeks Demonstrated lack of allograft efficacy to heal RDEB wounds - 13 patients with a total of 15 chronic wounds were treated with an allograft product, including Apligraf and Dermagraft - Only 7% (1/15 treated wounds) remained healed after 12 weeks, and % (/15 treated wounds) remained healed after 24 weeks UNTREATED CHRONIC WOUND: ARM BASELINE 3 MONTHS 6 MONTHS Natural history study supports clinical endpoints comparison Average duration of untreated chronic wounds > 7 years 24 24

25 EB-11 Case Study Baseline 3 months 6 months 12 months 24 months 24 months Anti-K1 Pab Anti-COl7A1 NC2 Mab Hoechst Anti-COl7A1 NC2 Mab Hoechst Anti-COl7A1 NC2 Mab Hoechst Anti-COl7A1 NC1 Pab Hoechst Anti-COl7A1 NC1 Pab Hoechst Anti-COl7A1 NC1 Pab Hoechst Anti-K14 Pab Anti-COl7A1 NC2 Mab Hoechst * Col7 Presence Anti-Loricrin Pab Anti-COl7A1 NC2 Mab Hoechst * Anchoring Fibrils Siprashvili, Zurab et al. "Safety And Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts In Patients With RDEB". JAMA (216): 188. Web. 25

26 Summary of Phase 1/2 Trial Results Clinical Observations (n=7) Wound Healing in EB-11 Treated Wounds v. Untreated Control Wounds Global Rating Scale Significant and durable wound Healing (>5% healed) in treated wounds Continuous type VII collagen expression >2 years post treatment No serious adverse events observed to date 26

27 EB-11 Phase 1/2 Patient Reported Outcomes (PROs) Presence of pain at wound site (% reported yes) Pre- 3 Month 6 Month 9 Month 12 Month Grafting 58.3% % 16.7% 2% % Itch at wound site (% reported yes) 66.7% 4.8% 16.7% 5% 25% Durability at wound site (% reported yes) 9% % % % % Ease of blistering at wound site (% reported yes) 83.3% % % % % 27

28 AIM Next Generation AAV Vector Platform Targeting CNS, skin, muscle, liver and other tissues 28

29 In vitro Infectivity Assay 24 Hours Post-transduction % Transfection Efficiency 676% 56% 643% 527% 36% 1% AAV9 AAV112 AAV114 AAV115 AAV116 AAV121 AAV9 AAV112 AAV114 AAV115 AAV116 AAV121 29

30 AIM Vectors Demonstrate Increased CNS Specificity TRANSDUCTION EFFICIENCY, % Brain AAV TRANSDUCTION EFFICIENCY, % Cervical Cord AAV TRANSDUCTION EFFICIENCY, % Lumbar Cord AAV TRANSDUCTION EFFICIENCY, % 12 Liver AAV Liver de-targeted 3

31 AIM Vector Platform Tissue Specific Therapeutic Targets CNS Disorders MPS Parkinsons Lung Diseases Cystic fibrosis COPD Asthma Liver Hemophilia Wilsons Heart Heart failure PVD Kidney Polycystic kidney disease Muscular dystrophies Duchenne Skin Disorders Wounds EB Hair Pigment Ability to specifically target tissue and disease 31