NASDAQ: ABEO

Transcription

1 NASDAQ: ABEO

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 10-K for the year ended December 31, 2016, 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 ofthis presentation, whetheras a result ofnew information,future developments orotherwise. 2

3 Company Highlights A world leader in rare disease therapies Strategic Focus on Rare Diseases Substantial unmet medical need to treat life threatening diseases caused by a defect in a single gene Orphan and Rare pediatric disease focus: shorter route to approval, and lower costs Opportunity to secure Priority Review Voucher (PRV) for rare pediatric diseases Three Clinical Programs in Phase I/II ABO-102: Sanfilippo syndrome Type A MPS IIIA. Lysosomal storage disease affecting children. ABO-101: Sanfilippo syndrome Type B MPS IIIB. Lysosomal storage disease affecting children. EB-101: Recessive dystrophic epidermolysis bullosa (RDEB). Severely fragile skin disease affecting children. Multiple Therapies soon Entering the Clinic Based on strong pre-clinical results, two additional programs are expected to begin Phase I/II by the end of 2017 including: ABO-201: Juvenile Batten disease (CLN3) and ABO-202: Infantile Batten disease (CLN1) Proprietary 2 nd Generation Vector Platform 60+ proprietary AAV vectors that uniquely enable the delivery of genes across the blood brain barrier Next generation chimera vector platform in development with increased gene delivery efficiency, reduced antibody affinity, enhanced ability to create immune responses and target tissue specifications Several Catalysts to Drive Significant Near Term Value Achieve fast track designation for additional programs Initiate ABO-102 for MPS IIIA trials at global sites Initiate and enroll 1 st patient in ABO-101 for MPS IIIB Phase 1/2 clinical studies Dose adolescents in EB-101 trial; secure orphan drug and rare pediatric disease designations 3

4 Rare Disease Pipeline 4

5 GARRETT Global Foundation Support Investors and ongoing supporters of Abeona GRAND The BATTEN FIGHTER Original founding foundations 5

6 Clinical-Stage Programs 6

7 FDA Orphan Products Designation EMA Orphan Drug Designation FDA Rare Pediatric Disease Designation FDA Fast Track ABO-102 SANFILIPPO SYNDROME TYPE A World leading clinical program for MPS IIIA 7

8 Sanfilippo Syndrome (MPS III) Rare lysosomal storage disease affecting children 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) Results in abnormal accumulation of glycosaminoglycans (GAGs) (sugars) Aggressive behavior, seizures, loss of speech/vision, inability to sleep 70% of children with MPS III do not reach age 18 Normal cell No approved treatments available Incidence is estimated to be 1 in 70,000 births Two ongoing clinical trials ABO-102 (scaav-sgsh) for MPS IIIA o Cohort 1 (n=3) completed, Cohort 2 enrollment has commenced ABO-101 (AAV-NAGLU) for MPS IIIB Recruitment anticipated shortly Conducted at Nationwide Children s Hospital, Columbus, OH Cell with lysosome deficiency 8

9 Clinical Trial Readiness MPS III Natural History Study normal range 25 subjects: 15 MPS IIIA & 10 MPS IIIB Established standards for biochemical (serum and CSF) studies and volumetric (MRI) relevant to the clinical trial Study visits baseline, 6- and 12-month assessments Validated neurocognitive and behavior outcome measures for MPS III clinical trials Leiter-3 Nonverbal-IQ Score over 6 months normal range Multiple patient cross-over into clinical trials Vineland Scale - Behavior Assessments over 1 year Truxal et al (2016) Mol Genet Metab, 119(3):

10 Phase 1/2 ABO-102 (scaav-sgsh) Clinical Trial for MPS IIIA Global open-label, dose-escalation gene transfer trial Phase 1/2 open-label, dose-escalation clinical trials - Cohort 1: 5 X vg/kg (n=3 subjects) ENROLLMENT COMPLETE - Cohort 2: 1 X vg/kg (n=3 subjects) ENROLLMENT COMPLETE - Additional enrollments at 2 global sites: Spain and Australia Primary objective is safety, with secondary efficacy endpoints - Reduction in Urine/CSF 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 - Pediatric Quality of Life Inventory 4.0 (PedsQL) - Brain MRI volumetric changes 10

11 Dose-dependent Reduction Observed in CSF Heparan Sulfate Reduction of CSF HS fragment indicates ABO-102 crosses the blood-brain barrier 0% Day 30 Day % 0. 6 % Reduction in CSF Heparan sulfate (HS) -20% -30% -40% -50% % Cohort 1 (N=3) Cohort 2 (N=2) n m o l/m L % -70% % % S c r e e n i n g D o s in g 3 0 D a y M o n t h 6 Cohort 1 (n=3) through Day 180 Cohort 2 (n=2) through Day 30 11

12 Consistent Reduction in Biomarkers of MPS IIIA Disease Pathology Total GAG and Urine heparan sulfate fragments are reduced post-treatment 10% Screening Day 30 Day 60 Day 90 Day 180 0% 0% % Reduction of Urine TOTAL GAG -10% -20% -30% -40% -50% -60% -70% Cohort 1 Cohort 2 % Reduction of Urine Heparan sulfate (HS) -10% -20% -30% -40% -50% -60% -70% -80% -90% Cohort 1 Cohort 2 Cohort 1 (n=3) through Day 180 Cohort 2 (n=2) through Day 30 (n=1) through Day 60 12

13 ABO-102 Reduced Liver Volume: Reduction of biophysical hallmarks of MPS IIIA disease pathology Not yet available cohort 1 cohort 2 Natural history study of 25 subjects with MPS III (Truxal et. al., 2016, Mol. Genet. Metab.) demonstrated that subjects had increased liver volumes averaging 116% at baseline that maintained over a year of follow-up. 13

14 ABO Evidence of Neurological Biopotency & Clinical Benefit Neurocognitive assessment Leiter-3 Nonverbal IQ Scale LEITER-3 WITH ABO-102 Study Natural History # subjects (n) Avg Change in Leiter* score over 6 months N = 8 * (± 2.7) Subject C N = (± 6) * 8 Natural history study subjects ages years old over 12 time points The Leiter International Performance Scale Third Edition (Leiter-3): test of nonverbal intellectual ability for ages 3 and above Does not require any translations for non-english speakers Is suitable for use in children with hearing deficits 14

15 ABO Evidence of Neurological Biopotency & Clinical Benefit Neurocognitive assessment Vineland Composite Score VINELAND SCORE WITH ABO-102 Study Natural History # subjects (n) Avg Change in Vineland score over 6 mo. N = 9 * -7.0 (± 1.9) Cohort 1 N = *9 Natural history study subjects age years old over 13 time points The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) measures: Adaptive behaviors Maladaptive behaviors Social and personal skills needed for everyday living 15

16 Summary of ABO-102 Clinical Data Demonstrates biopotency and early signals of neurocognitive and behavioral improvements Dosing in Cohort 2 demonstrated positive dose-dependent response Evidence for biopotency and clinical benefit including - Reduction of liver volumes at 30 and 180 days - Decreased CSF GAGs (HS) fragments at 30 and 180 days - Decreased urinary GAGS (HS fragments and Total GAGs) at 30 and 90 days Early positive signals of neurocognitive assessments - Includes early signs of improved non-verbal IQ scores - Stabilization of previously declining Vineland measurements Safety: ABO-102 is well tolerated to date - No serious adverse events (n=6 through 1,139 days follow-up) - Serum transaminases initially decline, and remain largely stable through 6 months post-injection - IFN-γ ELISpot stable through 3 patients 16

17 Lysosomal Storage Disease Gene Therapy Potential neurocognitive treatment outcome paradigms Functional Cure Normal Development Disease stabilization Development Score Disease Onset Delay Subjects enrolled in Cohort 1 Subjects enrolled in Cohort 2 Disease attenuation Age (years) Source: Fu et al (2011) Correction of Neurological Disease of Mucopolysaccharidosis IIIB in adult mice by raav9 Trans-Blood-Brain Barrier Gene Delivery, Mol. Ther 19 17

18 FDA Orphan Products Designation EMA Orphan Drug Designation FDA Rare Pediatric Disease Designation ABO-101 SANFILIPPO SYNDROME TYPE B World leading clinical program for MPS IIIB 18

19 ABO-101 for Treatment of Subject with MPS IIIB Abeona s third gene therapy in clinical trials Pre-clinical data - ABO-101 Single iv infusion of ABO-101 at 4-6 weeks of age normalized the survival in MPSIIIB mice - Single IV Delivery of ABO-101 induced clearance of lysosomal GAG storage inthe CNSandsomatictissues - 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=6-9 pts via intravenous injection - Cohort 1 (Low Dose): 2 X vg/kg (n=3 subjects) - Cohort 2 (High Dose): 5 X vg/kg (n=3-6 subjects) - Clinical sites: United States, Spain - Enrollment to commence shortly Source: Fu et al (2011) Correction of Neurological Disease of Mucopolysaccharidosis IIIB in adult mice by raav9 Trans-Blood-Brain Barrier Gene Delivery, Mol. Ther 19 19

20 FDA Orphan Products Designation EMA Orphan Drug Designation FDA Rare Pediatric Disease Designation EB-101 Recessive Dystrophic Epidermolysis Bullosa Clinical program for severe form of Epidermolysis Bullosa 20

21 EB-101: Gene Therapy for Patients with Epidermolysis Bullosa (EB) Rare and devastating skin disease Group of devastating inherited connective tissue diseases; characterized by skin blisters and erosions Recessive Dystrophic Epidermolysis Bullosa (RDEB) is caused by the absence of the COL7A1 gene (encodes type 7 collagen to anchors skin to the underlying stroma) No FDA approved therapies currently available Prevalence of EB: ~30,000-40,000; RDEB: ~2,500-3,000 in the US alone Ongoing Phase 1/2 clinical trial Conducted at Stanford University School of Medicine Primary Endpoint: Safety, wound healing compared to baseline Secondary Endpoint: Expression of type VII collagen, pain, itching, quality of life Butterfly skin patient 21

22 Supportive Natural History Study 128 RDEB Subjects Multi-year Enrollment complete: 1,436 wounds (1,041 recurrent wounds/395 chronic open wounds) UNTREATED CHRONIC WOUND: ARM BASELINE 3 MONTHS 6 MONTHS 100% 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 0% (0/15 treated wounds) remained healed after 24 weeks UNTREATED RECURRENT WOUND: CHEST BASELINE 2 WEEKS 4 WEEKS Natural history study supports clinical endpoints comparison 22

23 EB-101 Autologous Gene Therapy for RDEB Subjects Genetically corrected autologous skin application EB-101: Ex-vivo Gene Therapy gene therapy correction of patient cells to replace COL7A1 cdna EB-101: gene-corrected skin treatment EB-101 ready for application 23

24 EB-101 Case Study Subject wounds pre- & post treatment Baseline 3 months 6 months 12 months 24 months 24 months Anti-K1 Pab Anti-COl7A1 NC2 Mab Hoechst Anti-K14 Pab Anti-COl7A1 NC2 Mab Hoechst Anti-COl7A1 NC2 Mab Anti-COl7A1 NC2 Mab Anti-COl7A1 NC1 Pab Anti-COl7A1 NC1 Pab Anti-COl7A1 NC1 Pab Hoechst Hoechst Hoechst Hoechst Hoechst Anti-Loricrin Pab Anti-COl7A1 NC2 Mab Hoechst

25 Summary of EB-101 Clinical Data EB-101 treated wounds remain closed >2 years Months Subjects Total EB-101 treated wounds (n) Wound healing >50% 100% (36/36) 89% (32/36) 83% (20/24) 88% (21/24) 100% (6/6) Untreated control wound healing >50% 0% (0/4) 0% (0/4) 0% (0/2) 0% (0/2) n/d EB- 101 Demonstrates Significant Wound Healing (greater than 50% healed) in Treated Wounds First Phase 1/2 clinical trial in progress for genetic correction of RDEB Seven RDEB patients successfully grafted with genetically corrected grafts Continuous type VII collagen expression confirmed up to 2 years post grafting Treatment well tolerated with no serious adverse events observed to date Long-term follow up is ongoing 25

26 AIM Vector Platform 2 nd generation and novel AAV products Natural AAV Serotypes Proprietary AIM Vector 26

27 AIM - Next Generation AAV Vector Platform Engineered designer vectors AIM Vector Platform Next generation AAV viral vector platform to target CNS, skin, muscle, liver and other tissues Over 60 novel AAV Capsids - multiple tissue platforms Key Advantages of AIM ü ü Increased gene delivery efficiency with new tissue tropisms Potential for redosing previously treated AAV subjects

28 AIM Vectors High Tropism for CNS After IV injection of 2e11 vg After direct CNS injection of 5E10 vg AAV9 AAV 303 AAV 934 AAV 308 AAV 208 AAV 123 Control AAV9 AAV423 AAV455 AAV 459 AAV897 Adult Mice Adult Mice 28

29 Pre-Clinical Programs 29

30 ABO-201 and ABO-202 Juvenile (CLN3) and Infantile (CLN1) Batten Diseases AAV pre-clinical development Batten disease 30

31 ABO 201 for Juvenile Batten Disease CLN3 Pre-IND meeting completed, clinical trial to commence shortly JBD - Autosomal recessive (inherited) mutation in the CLN3 gene Initially presents as blindness, progressing to behavioral issues, sleep disturbances, seizures, cognitive loss, motor abnormalities, premature death (late teens-early 20s) Neurodegeneration occurs primarily in thalamus, cortex, and hippocampus, althoughinclusionsare observed throughout the CNS Estimated incidence of 1:100,000 births Pre-clinicalresults mirrored datain MPS IIIA & B; normalization of motor functionand survival Research conducted at the University of Nebraska Medical Center ABO-201: Human clinical trials anticipated in 2017 at University of Rochester MedicalCenter Ongoing Batten Disease Natural History Study at University of Rochester Medical Center Source: Moving towards therapies for Juvenile batten disease, Experimental Neurology,

32 ABO 202 for Infantile Batten Disease CLN1 Clinical trial to commence in early 2018 Autosomal recessive (inherited) mutation in the CLN1 gene Diagnosed between ages 6 months and 2 years with early death before age 5 - Affected children fail to thrive and have microcephaly; also typical are short, sharp muscle contradictions called myoclonic jerks Preclinical work shows promising efficacy in INCL mice after delivery of a functioning copy of the CLN1 gene to cells of the central nervous system - Extended survival and preserved strength when administered early in the disease course - Research conducted at the University of North Carolina at Chapel Hill ABO 202 Human clinical trials anticipated 1H

33 Manufacturing Strategy Parallel paths enable clinical trial and commercial long-term sustainable supply A combination of third-party and internal manufacturing sources to ensure long-term continuous supply for domestic and international clinical trials as well as commercial demand. Third Parties Utilizing established Contract Manufacturing Organizations (CMOs) Nationwide Children s Hospital, UC Davis & Stanford Ongoing tech transfer and process development for commercial scale Leverages existing relationships to develop clinical POC Internal Manufacturing Establish company s own manufacturing facility Manufacturing is a strategic capability asset Secures supply chain control and business continuity - internal QA/QC Increases supply capacity for key therapies and potentially other products 33

34 Financial Overview Cash (at March 31, 2017) Cash Used in Operations (Qtr Ended March 31, 2017) Debt Primary Common Shares Out (at March 31, 2017) $63.2 million $5.9 million No Debt ~40 million 34

35 Management, Directors & Scientific/Clinical Advisory Boards Management & Board of Directors Steven H. Rouhandeh - Executive Chairman & Director Timothy J. Miller, Ph.D. - President and Chief Executive Officer & Director Jeffrey B. Davis - Chief Operating Officer Mark J. Alvino - Director Stephen B. Howell, M.D. - Director Todd Wider, M.D. - Director Scientific & Clinical Advisory Board Timothy J. Miller, Ph.D. - Abeona Therapeutics Maria Escolar, M.D. - Pittsburgh Children s Hosptial S. Kaye Spratt, Ph.D. - Abeona Therapeutics Brian Kaspar, Ph.D. - Nationwide Children s Hospital John Cooper, Ph.D. - Univ. California, San Diego Erika Augustine, M.D. - University of Rochester Jonathon Mink, M.D., Ph.D. - University of Rochester Steven Gray, Ph.D. - University of North Carolina Kevin Flanigan, M.D. - Nationwide Children s Hospital Tammy Kielian, Ph.D. - University of Nebraska Medical Center Douglas McCarty, Ph.D. - Nationwide Children s Hospital 35

36 Company Highlights A world leader in rare disease therapies Strategic Focus on Rare Diseases Substantial unmet medical need to treat life threatening diseases caused by a defect in a single gene Orphan and Rare pediatric disease focus: shorter route to approval, and lower costs Opportunity to secure Priority Review Voucher (PRV) for rare pediatric diseases Three Clinical Programs in Phase I/II ABO-102: Sanfilippo syndrome Type A MPS IIIA. Lysosomal storage disease affecting children. ABO-101: Sanfilippo syndrome Type B MPS IIIB. Lysosomal storage disease affecting children. EB-101: Recessive dystrophic epidermolysis bullosa (RDEB). Severely fragile skin disease affecting children. Multiple Therapies soon Entering the Clinic Based on strong pre-clinical results, two additional programs are expected to begin Phase I/II by the end of 2017 including: ABO-201: Juvenile Batten disease (CLN3) and ABO-202: Infantile Batten disease (CLN1) Proprietary 2 nd Generation Vector Platform 60+ proprietary AAV vectors that uniquely enable the delivery of genes across the blood brain barrier Next generation chimera vector platform in development with increased gene delivery efficiency, reduced antibody affinity, enhanced ability to create immune responses and target tissue specifications Several Catalysts to Drive Significant Near Term Value Achieve fast track designation for additional programs Initiate ABO-102 for MPS IIIA trials at global sites Initiate and enroll 1 st patient in ABO-101 for MPS IIIB Phase 1/2 clinical studies Dose adolescents in EB-101 trial; secure orphan drug and rare pediatric disease designations 36